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Sample records for lec biological design

  1. Genomic rearrangements and functional diversification of lecA and lecB lectin-coding regions impacting the efficacy of glycomimetics directed against Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Amine M Boukerb

    2016-05-01

    Full Text Available LecA and LecB tetrameric lectins take part in oligosaccharide-mediated adhesion-processes of Pseudomonas aeruginosa. Glycomimetics have been designed to block these interactions. The great versatility of P. aeruginosa suggests that the range of application of these glycomimetics could be restricted to genotypes with particular lectin types. The likelihood of having genomic and genetic changes impacting LecA and LecB interactions with glycomimetics such as galactosylated and fucosylated calix[4]arene was investigated over a collection of strains from the main clades of P. aeruginosa. Lectin types were defined, and their ligand specificities were inferred. These analyses showed a loss of lecA among the PA7 clade. Genomic changes impacting lec loci were thus assessed using strains of this clade, and by making comparisons with the PAO1 genome. The lecA regions were found challenged by phage attacks and PAGI-2 (genomic island integrations. A prophage was linked to the loss of lecA. The lecB regions were found less impacted by such rearrangements but greater lecB than lecA genetic divergences were recorded. Sixteen combinations of LecA and LecB types were observed. Amino acid variations were mapped on PAO1 crystal structures. Most significant changes were observed on LecBPA7, and found close to the fucose binding site. Glycan array analyses were performed with purified LecBPA7. LecBPA7 was found less specific for fucosylated oligosaccharides than LecBPAO1, with a preference for H type 2 rather than type 1, and Lewisa rather than Lewisx. Comparison of the crystal structures of LecBPA7 and LecBPAO1 in complex with Lewisa showed these changes in specificity to have resulted from a modification of the water network between the lectin, galactose and GlcNAc residues. Incidence of these modifications on the interactions with calix[4]arene glycomimetics at the cell level was investigated. An aggregation test was used to establish the efficacy of these ligands

  2. 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.

  3. Accrual of ROCs LECs and REGOs

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-07-01

    This report summarises the findings of a project to identify the technical and administrative difficulties experienced by microgenerators in accessing the benefits of Renewables Obligation Certificates (ROCs), Levy Exemption Certificates (LECs) and Renewable Electricity Guarantees of Origin (REGO). These include cost, administrative complexity and financial risk. Changes allowing bulk processing, meter data provision, sell and buyback contracts, and alignment of ROCs, LECs and REGOs are discussed as well as making the schemes more customer friendly. The background to the project is traced, and an overview of the processes associated with gaining ROCs, LECs and REGOs is presented.

  4. MEMBRANE LEc EXPRESSION IN BREAST CANCER CELLS

    Directory of Open Access Journals (Sweden)

    Ya. A. Udalova

    2009-01-01

    Full Text Available Affine chromatography was used to isolate Lec antibodies from the sera of a healthy female donor with the high titers of these anti- bodies, which were labeled with biotin. The study enrolled 51 patients with primary breast cancer (BC. Antigen expression was found by immunohistochemistry and flow cytometry. With these two techniques being used, the detection rate of Lec expression in BC cells was 65% (33/51; the antigen was most frequently found by flow cytometry as compared with immunohistochemistry: 72 and 58% of cases, respectively.

  5. Paradigms for biologically inspired design

    DEFF Research Database (Denmark)

    Lenau, T. A.; Metzea, A.-L.; Hesselberg, T.

    2018-01-01

    engineering, medical engineering, nanotechnology, photonics,environmental protection and agriculture. However, a major obstacle for the wider use of biologically inspired design isthe knowledge barrier that exist between the application engineers that have insight into how to design suitable productsand......Biologically inspired design is attracting increasing interest since it offers access to a huge biological repository of wellproven design principles that can be used for developing new and innovative products. Biological phenomena can inspireproduct innovation in as diverse areas as mechanical...... the biologists with detailed knowledge and experience in understanding how biological organisms function in theirenvironment. The biologically inspired design process can therefore be approached using different design paradigmsdepending on the dominant opportunities, challenges and knowledge characteristics...

  6. Towards Logical Designs In Biology

    Indian Academy of Sciences (India)

    Administrator

    thetic biology that envisions integrating designed circuits into living ... research student in the .... integrating an odd number of NOT gates in a circular fashion such that the .... end is rational design where the targeting of gene mutations to.

  7. Cucumis sativus L-type lectin receptor kinase (CsLecRK) gene family response to Phytophthora melonis, Phytophthora capsici and water immersion in disease resistant and susceptible cucumber cultivars.

    Science.gov (United States)

    Wu, Tingquan; Wang, Rui; Xu, Xiaomei; He, Xiaoming; Sun, Baojuan; Zhong, Yujuan; Liang, Zhaojuan; Luo, Shaobo; Lin, Yu'e

    2014-10-10

    L-type lectin receptor kinase (LecRK) proteins are an important family involved in diverse biological processes such as pollen development, senescence, wounding, salinity and especially in innate immunity in model plants such as Arabidopsis and tobacco. Till date, LecRK proteins or genes of cucumber have not been reported. In this study, a total of 25 LecRK genes were identified in the cucumber genome, unequally distributed across its seven chromosomes. According to similarity comparison of their encoded proteins, the Cucumis sativus LecRK (CsLecRK) genes were classified into six major clades (from Clade I to CladeVI). Expression of CsLecRK genes were tested using QRT-PCR method and the results showed that 25 CsLecRK genes exhibited different responses to abiotic (water immersion) and biotic (Phytophthora melonis and Phytophthora capsici inoculation) stresses, as well as that between disease resistant cultivar (JSH) and disease susceptible cultivar (B80). Among the 25 CsLecRK genes, we found CsLecRK6.1 was especially induced by P. melonis and P. capsici in JSH plants. All these results suggested that CsLecRK genes may play important roles in biotic and abiotic stresses. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. 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.

  9. LecRK-V, an L-type lectin receptor kinase in Haynaldia villosa, plays positive role in resistance to wheat powdery mildew.

    Science.gov (United States)

    Wang, Zongkuan; Cheng, Jiangyue; Fan, Anqi; Zhao, Jia; Yu, Zhongyu; Li, Yingbo; Zhang, Heng; Xiao, Jin; Muhammad, Faheem; Wang, Haiyan; Cao, Aizhong; Xing, Liping; Wang, Xiue

    2018-01-01

    Plant sense potential microbial pathogen using pattern recognition receptors (PRRs) to recognize pathogen-associated molecular patterns (PAMPs). The Lectin receptor-like kinase genes (LecRKs) are involved in various cellular processes mediated by signal transduction pathways. In the present study, an L-type lectin receptor kinase gene LecRK-V was cloned from Haynaldia villosa, a diploid wheat relative which is highly resistant to powdery mildew. The expression of LecRK-V was rapidly up-regulated by Bgt inoculation and chitin treatment. Its transcript level was higher in the leaves than in roots, culms, spikes and callus. Single-cell transient overexpression of LecRK-V led to decreased haustorium index in wheat variety Yangmai158, which is powdery mildew susceptible. Stable transformation LecRK-V into Yangmai158 significantly enhanced the powdery mildew resistance at both seedling and adult stages. At seedling stage, the transgenic line was highly resistance to 18 of the tested 23 Bgt isolates, hypersensitive responses (HR) were observed for 22 Bgt isolates, and more ROS at the Bgt infection sites was accumulated. These indicated that LecRK-V confers broad-spectrum resistance to powdery mildew, and ROS and SA pathways contribute to the enhanced powdery mildew resistance in wheat. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  10. Arabidopsis Lectin Receptor Kinases LecRK-IX.1 and LecRK-IX.2 Are Functional Analogs in Regulating Phytophthora Resistance and Plant Cell Death.

    Science.gov (United States)

    Wang, Yan; Cordewener, Jan H G; America, Antoine H P; Shan, Weixing; Bouwmeester, Klaas; Govers, Francine

    2015-09-01

    L-type lectin receptor kinases (LecRK) are potential immune receptors. Here, we characterized two closely-related Arabidopsis LecRK, LecRK-IX.1 and LecRK-IX.2, of which T-DNA insertion mutants showed compromised resistance to Phytophthora brassicae and Phytophthora capsici, with double mutants showing additive susceptibility. Overexpression of LecRK-IX.1 or LecRK-IX.2 in Arabidopsis and transient expression in Nicotiana benthamiana increased Phytophthora resistance but also induced cell death. Phytophthora resistance required both the lectin domain and kinase activity, but for cell death, the lectin domain was not needed. Silencing of the two closely related mitogen-activated protein kinase genes NbSIPK and NbNTF4 in N. benthamiana completely abolished LecRK-IX.1-induced cell death but not Phytophthora resistance. Liquid chromatography-mass spectrometry analysis of protein complexes coimmunoprecipitated in planta with LecRK-IX.1 or LecRK-IX.2 as bait, resulted in the identification of the N. benthamiana ABC transporter NbPDR1 as a potential interactor of both LecRK. The closest homolog of NbPDR1 in Arabidopsis is ABCG40, and coimmunoprecipitation experiments showed that ABCG40 associates with LecRK-IX.1 and LecRK-IX.2 in planta. Similar to the LecRK mutants, ABCG40 mutants showed compromised Phytophthora resistance. This study shows that LecRK-IX.1 and LecRK-IX.2 are Phytophthora resistance components that function independent of each other and independent of the cell-death phenotype. They both interact with the same ABC transporter, suggesting that they exploit similar signal transduction pathways.

  11. New insights on the evolution of Leafy cotyledon1 (LEC1) type genes in vascular plants.

    Science.gov (United States)

    Cagliari, Alexandro; Turchetto-Zolet, Andreia Carina; Korbes, Ana Paula; Maraschin, Felipe Dos Santos; Margis, Rogerio; Margis-Pinheiro, Marcia

    2014-01-01

    NF-Y is a conserved oligomeric transcription factor found in all eukaryotes. In plants, this regulator evolved with a broad diversification of the genes coding for its three subunits (NF-YA, NF-YB and NF-YC). The NF-YB members can be divided into Leafy Cotyledon1 (LEC1) and non-LEC1 types. Here we presented a comparative genomic study using phylogenetic analyses to validate an evolutionary model for the origin of LEC-type genes in plants and their emergence from non-LEC1-type genes. We identified LEC1-type members in all vascular plant genomes, but not in amoebozoa, algae, fungi, metazoa and non-vascular plant representatives, which present exclusively non-LEC1-type genes as constituents of their NF-YB subunits. The non-synonymous to synonymous nucleotide substitution rates (Ka/Ks) between LEC1 and non-LEC1-type genes indicate the presence of positive selection acting on LEC1-type members to the fixation of LEC1-specific amino acid residues. The phylogenetic analyses demonstrated that plant LEC1-type genes are evolutionary divergent from the non-LEC1-type genes of plants, fungi, amoebozoa, algae and animals. Our results point to a scenario in which LEC1-type genes have originated in vascular plants after gene expansion in plants. We suggest that processes of neofunctionalization and/or subfunctionalization were responsible for the emergence of a versatile role for LEC1-type genes in vascular plants, especially in seed plants. LEC1-type genes besides being phylogenetic divergent also present different expression profile when compared with non-LEC1-type genes. Altogether, our data provide new insights about the LEC1 and non-LEC1 evolutionary relationship during the vascular plant evolution. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Biological design in science classrooms

    Science.gov (United States)

    Scott, Eugenie C.; Matzke, Nicholas J.

    2007-01-01

    Although evolutionary biology is replete with explanations for complex biological structures, scientists concerned about evolution education have been forced to confront “intelligent design” (ID), which rejects a natural origin for biological complexity. The content of ID is a subset of the claims made by the older “creation science” movement. Both creationist views contend that highly complex biological adaptations and even organisms categorically cannot result from natural causes but require a supernatural creative agent. Historically, ID arose from efforts to produce a form of creationism that would be less vulnerable to legal challenges and that would not overtly rely upon biblical literalism. Scientists do not use ID to explain nature, but because it has support from outside the scientific community, ID is nonetheless contributing substantially to a long-standing assault on the integrity of science education. PMID:17494747

  13. Design principles in biological networks

    Science.gov (United States)

    Goyal, Sidhartha

    Much of biology emerges from networks of interactions. Even in a single bacterium such as Escherichia coli, there are hundreds of coexisting gene and protein networks. Although biological networks are the outcome of evolution, various physical and biological constraints limit their functional capacity. The focus of this thesis is to understand how functional constraints such as optimal growth in mircoorganisms and information flow in signaling pathways shape the metabolic network of bacterium E. coli and the quorum sensing network of marine bacterium Vibrio harveyi, respectively. Metabolic networks convert basic elemental sources into complex building-blocks eventually leading to cell's growth. Therefore, typically, metabolic pathways are often coupled both by the use of a common substrate and by stoichiometric utilization of their products for cell growth. We showed that such a coupled network with product-feedback inhibition may exhibit limit-cycle oscillations which arise via a Hopf bifurcation. Furthermore, we analyzed several representative metabolic modules and find that, in all cases, simple product-feedback inhibition allows nearly optimal growth, in agreement with the predicted growth-rate by the flux-balance analysis (FBA). Bacteria have fascinating and diverse social lives. They display coordinated group behaviors regulated by quorum sensing (QS) systems. The QS circuit of V. harveyi integrates and funnels different ecological information through a common phosphorelay cascade to a set of small regulatory RNAs (sRNAs) that enables collective behavior. We analyzed the signaling properties and information flow in the QS circuit, which provides a model for information flow in signaling networks more generally. A comparative study of post-transcriptional and conventional transcriptional regulation suggest a niche for sRNAs in allowing cells to transition quickly yet reliably between distinct states. Furthermore, we develop a new framework for analyzing signal

  14. Experimental loop for SH2 (LECS)

    International Nuclear Information System (INIS)

    Strehar, N.R.; Bruzzoni, Pablo; Moras, J.J.; Cogozzo, E.O.

    1981-01-01

    An experimental loop is described for circulation of SH 2 that operates at 2 x 10 6 Pascal and 33 deg C. It was designed and constructed with the purpose of experimentally studying the hydraulic instability phenomenon that can be detected in cold isotopic exchange columns in the Girdler-Sulfide (GS) process of heavy water production. The main features of the different components of the loop are described, as well as the materials, the measurement and control instruments and the auxiliary equipment used, and finally the measuring methods to qualify and quantify the formation of froth. Furthermore, the loop's transportable metallic container is described, which allows to transport and connect it to CNEA's experimental heavy water plant or to any other heavy water plants using the GS method. Some tests made with inert gases that intended to verify the equipment's performance and to select the most adequate sieve trays for its operation are discussed. (M.E.L.) [es

  15. Bioinspiration: applying mechanical design to experimental biology.

    Science.gov (United States)

    Flammang, Brooke E; Porter, Marianne E

    2011-07-01

    The production of bioinspired and biomimetic constructs has fostered much collaboration between biologists and engineers, although the extent of biological accuracy employed in the designs produced has not always been a priority. Even the exact definitions of "bioinspired" and "biomimetic" differ among biologists, engineers, and industrial designers, leading to confusion regarding the level of integration and replication of biological principles and physiology. By any name, biologically-inspired mechanical constructs have become an increasingly important research tool in experimental biology, offering the opportunity to focus research by creating model organisms that can be easily manipulated to fill a desired parameter space of structural and functional repertoires. Innovative researchers with both biological and engineering backgrounds have found ways to use bioinspired models to explore the biomechanics of organisms from all kingdoms to answer a variety of different questions. Bringing together these biologists and engineers will hopefully result in an open discourse of techniques and fruitful collaborations for experimental and industrial endeavors.

  16. Biological Systems Thinking for Control Engineering Design

    Directory of Open Access Journals (Sweden)

    D. J. Murray-Smith

    2004-01-01

    Full Text Available Artificial neural networks and genetic algorithms are often quoted in discussions about the contribution of biological systems thinking to engineering design. This paper reviews work on the neuromuscular system, a field in which biological systems thinking could make specific contributions to the development and design of automatic control systems for mechatronics and robotics applications. The paper suggests some specific areas in which a better understanding of this biological control system could be expected to contribute to control engineering design methods in the future. Particular emphasis is given to the nonlinear nature of elements within the neuromuscular system and to processes of neural signal processing, sensing and system adaptivity. Aspects of the biological system that are of particular significance for engineering control systems include sensor fusion, sensor redundancy and parallelism, together with advanced forms of signal processing for adaptive and learning control. 

  17. Leveraging advances in biology to design biomaterials

    Science.gov (United States)

    Darnell, Max; Mooney, David J.

    2017-12-01

    Biomaterials have dramatically increased in functionality and complexity, allowing unprecedented control over the cells that interact with them. From these engineering advances arises the prospect of improved biomaterial-based therapies, yet practical constraints favour simplicity. Tools from the biology community are enabling high-resolution and high-throughput bioassays that, if incorporated into a biomaterial design framework, could help achieve unprecedented functionality while minimizing the complexity of designs by identifying the most important material parameters and biological outputs. However, to avoid data explosions and to effectively match the information content of an assay with the goal of the experiment, material screens and bioassays must be arranged in specific ways. By borrowing methods to design experiments and workflows from the bioprocess engineering community, we outline a framework for the incorporation of next-generation bioassays into biomaterials design to effectively optimize function while minimizing complexity. This framework can inspire biomaterials designs that maximize functionality and translatability.

  18. Lectin receptor kinase LecRK-b2 localizes to plasma membrane and ...

    African Journals Online (AJOL)

    -b2, has been characterized. Confocal microscopy images showed that the LecRK-b2-GFP fusion protein is localized to plasma membrane. The results of yeast 2 hybrid showed that lectin domain of LecRK-b2 had selfinteraction, while the ...

  19. An engineering design approach to systems biology.

    Science.gov (United States)

    Janes, Kevin A; Chandran, Preethi L; Ford, Roseanne M; Lazzara, Matthew J; Papin, Jason A; Peirce, Shayn M; Saucerman, Jeffrey J; Lauffenburger, Douglas A

    2017-07-17

    Measuring and modeling the integrated behavior of biomolecular-cellular networks is central to systems biology. Over several decades, systems biology has been shaped by quantitative biologists, physicists, mathematicians, and engineers in different ways. However, the basic and applied versions of systems biology are not typically distinguished, which blurs the separate aspirations of the field and its potential for real-world impact. Here, we articulate an engineering approach to systems biology, which applies educational philosophy, engineering design, and predictive models to solve contemporary problems in an age of biomedical Big Data. A concerted effort to train systems bioengineers will provide a versatile workforce capable of tackling the diverse challenges faced by the biotechnological and pharmaceutical sectors in a modern, information-dense economy.

  20. The Pseudomonas aeruginosa lectin LecA triggers host cell signalling by glycosphingolipid-dependent phosphorylation of the adaptor protein CrkII.

    Science.gov (United States)

    Zheng, Shuangshuang; Eierhoff, Thorsten; Aigal, Sahaja; Brandel, Annette; Thuenauer, Roland; de Bentzmann, Sophie; Imberty, Anne; Römer, Winfried

    2017-07-01

    The human pathogen Pseudomonas aeruginosa induces phosphorylation of the adaptor protein CrkII by activating the non-receptor tyrosine kinase Abl to promote its uptake into host cells. So far, specific factors of P. aeruginosa, which induce Abl/CrkII signalling, are entirely unknown. In this research, we employed human lung epithelial cells H1299, Chinese hamster ovary cells and P. aeruginosa wild type strain PAO1 to study the invasion process of P. aeruginosa into host cells by using microbiological, biochemical and cell biological approaches such as Western Blot, immunofluorescence microscopy and flow cytometry. Here, we demonstrate that the host glycosphingolipid globotriaosylceramide, also termed Gb3, represents a signalling receptor for the P. aeruginosa lectin LecA to induce CrkII phosphorylation at tyrosine 221. Alterations in Gb3 expression and LecA function correlate with CrkII phosphorylation. Interestingly, phosphorylation of CrkII Y221 occurs independently of Abl kinase. We further show that Src family kinases transduce the signal induced by LecA binding to Gb3, leading to Crk Y221 phosphorylation. In summary, we identified LecA as a bacterial factor, which utilizes a so far unrecognized mechanism for phospho-CrkII Y221 induction by binding to the host glycosphingolipid receptor Gb3. The LecA/Gb3 interaction highlights the potential of glycolipids to mediate signalling processes across the plasma membrane and should be further elucidated to gain deeper insights into this non-canonical mechanism of activating host cell processes. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Set membership experimental design for biological systems

    Directory of Open Access Journals (Sweden)

    Marvel Skylar W

    2012-03-01

    Full Text Available Abstract Background Experimental design approaches for biological systems are needed to help conserve the limited resources that are allocated for performing experiments. The assumptions used when assigning probability density functions to characterize uncertainty in biological systems are unwarranted when only a small number of measurements can be obtained. In these situations, the uncertainty in biological systems is more appropriately characterized in a bounded-error context. Additionally, effort must be made to improve the connection between modelers and experimentalists by relating design metrics to biologically relevant information. Bounded-error experimental design approaches that can assess the impact of additional measurements on model uncertainty are needed to identify the most appropriate balance between the collection of data and the availability of resources. Results In this work we develop a bounded-error experimental design framework for nonlinear continuous-time systems when few data measurements are available. This approach leverages many of the recent advances in bounded-error parameter and state estimation methods that use interval analysis to generate parameter sets and state bounds consistent with uncertain data measurements. We devise a novel approach using set-based uncertainty propagation to estimate measurement ranges at candidate time points. We then use these estimated measurements at the candidate time points to evaluate which candidate measurements furthest reduce model uncertainty. A method for quickly combining multiple candidate time points is presented and allows for determining the effect of adding multiple measurements. Biologically relevant metrics are developed and used to predict when new data measurements should be acquired, which system components should be measured and how many additional measurements should be obtained. Conclusions The practicability of our approach is illustrated with a case study. This

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

    Science.gov (United States)

    Smolke, Christina D; Silver, Pamela A

    2011-03-18

    Synthetic biology aims to make the engineering of biology faster and more predictable. In contrast, systems biology focuses on the interaction of myriad components and how these give rise to the dynamic and complex behavior of biological systems. Here, we examine the synergies between these two fields. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. 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.

  4. Biologically inspired coupled antenna beampattern design

    Energy Technology Data Exchange (ETDEWEB)

    Akcakaya, Murat; Nehorai, Arye, E-mail: makcak2@ese.wustl.ed, E-mail: nehorai@ese.wustl.ed [Department of Electrical and Systems Engineering, Washington University in St Louis, St Louis, MO 63130 (United States)

    2010-12-15

    We propose to design a small-size transmission-coupled antenna array, and corresponding radiation pattern, having high performance inspired by the female Ormia ochracea's coupled ears. For reproduction purposes, the female Ormia is able to locate male crickets' call accurately despite the small distance between its ears compared with the incoming wavelength. This phenomenon has been explained by the mechanical coupling between the Ormia's ears, which has been modeled by a pair of differential equations. In this paper, we first solve these differential equations governing the Ormia ochracea's ear response, and convert the response to the pre-specified radio frequencies. We then apply the converted response of the biological coupling in the array factor of a uniform linear array composed of finite-length dipole antennas, and also include the undesired electromagnetic coupling due to the proximity of the elements. Moreover, we propose an algorithm to optimally choose the biologically inspired coupling for maximum array performance. In our numerical examples, we compute the radiation intensity of the designed system for binomial and uniform ordinary end-fire arrays, and demonstrate the improvement in the half-power beamwidth, sidelobe suppression and directivity of the radiation pattern due to the biologically inspired coupling.

  5. Lectin receptor kinase LecRK-b2 localizes to plasma membrane and ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-07-20

    Jul 20, 2009 ... Furthermore, the recombinant LecRK-b2 protein exhibited autophosphorylation ... absence of ligand (Giranton et al., 2000; Shimosato et al.,. 2007), while some ..... Elicitin and Mediates INF1-induced Cell Death. Planta, 228: ...

  6. Creative design inspired by biological knowledge: Technologies and methods

    Science.gov (United States)

    Tan, Runhua; Liu, Wei; Cao, Guozhong; Shi, Yuan

    2018-05-01

    Biological knowledge is becoming an important source of inspiration for developing creative solutions to engineering design problems and even has a huge potential in formulating ideas that can help firms compete successfully in a dynamic market. To identify the technologies and methods that can facilitate the development of biologically inspired creative designs, this research briefly reviews the existing biological-knowledge-based theories and methods and examines the application of biological-knowledge-inspired designs in various fields. Afterward, this research thoroughly examines the four dimensions of key technologies that underlie the biologically inspired design (BID) process. This research then discusses the future development trends of the BID process before presenting the conclusions.

  7. Engineering Design of an Adaptive Leg Prosthesis Using Biological Principles

    DEFF Research Database (Denmark)

    Lenau, Torben Anker; Dentel, Andy; Invarsdottir, Thorunn

    2010-01-01

    The biomimetic design process is explored through a design case: An adaptive leg prosthesis. The aim is to investigate if the biomimetic design process can be carried out with a minimum of biological knowledge and without using advanced design methods. In the design case biomimetic design was suc...... was successfully carried out using library search resulting in 14 biological analogies for the design problem 'shape adaption'. It is proposed that search results are handled using special cards describing the biological phenomena and the functional principles....

  8. Cross-sensitivity of X-ray-hypersensitive cells derived from LEC strain rats to DNA-damaging agents

    International Nuclear Information System (INIS)

    Okui, T.; Endoh, D.; Arai, S.; Isogai, E.; Hayashi, M.

    1996-01-01

    The cross-sensitivity of X-ray-hypersensitive lung fibroblasts from LEC strain (LEC) rats to other DNA-damaging agents was examined. The LEC cells were 2- to 3-fold more sensitive to bleomycin (BLM) that induces DNA double-strand breaks, and to a cross-linking agent, mitomycin C, than the cells from WKAH strain (WKAH) rats, while they were slightly sensitive to alkylating agents, ethyl nitrosourea and N-methyl-N'-nitro-N-nitrosoguanidine, but not to UV-irradiation. Although no difference was observed in the initial yields of DNA double-strand breaks induced by BLM between LEC and WKAH cells, the repair process of DNA double-strand breaks was significantly slower in LEC cells than in WKAH cells

  9. Chemical composition of the essential oil of Cinnamomum cambodianum H. Lec.

    NARCIS (Netherlands)

    Dung, N.X.; Sothy, N.; Lo, V.N.; Leclercq, P.A.

    1993-01-01

    The essential oil of the wood of Cinnamomum cambodianum H. Lec. has been analyzed by a combination of GC and GC/MS. Twenty-seven components have been identified of which the major ones were found to be a-terpineol (33.4%), linalool (22.4%) and terpinen-4-ol (13.3%)

  10. Abnormal G1 arrest in the cell lines from LEC strain rats after X-irradiation

    International Nuclear Information System (INIS)

    Hayashi, M.; Uehara, K.; Kirisawa, R.; Endoh, D.; Arai, S.; Okui, T.

    1997-01-01

    The effect of X-irradiation of cell lines from LEC and WKAH strain rats on a progression o cell cycle was investigated. When WKAH rat ells were exposed to 5 Gy of X-rays and their cell cycle distribution was determined by a flow cytometer, the proportion of S-phase cells decrease and that of G2/M-phase cells in creased at 8 hr post-irradiation. At 18 and 24 hr post-irradiation, approximately 80% of the cells appeared in the G1 phase. On the contrary, the proportion of S-phase cells increased and that of G1-phase cells decreased in LEC rats during 8-24 hr post-irradiation, compared with that at 0 hr post-irradiation. Thus, radiation-induced delay in the progression from the G1 phase to S phase (G1 arrest) was observed inWKAH rat cells but not in LEC rat cells. In the case of WKAH rat cells, the intensities of the bands of p53 protein increased at 1 and 2 hr after X-irradiation at 5 Gy, compared with those of un-irradiated cells and at 0 hr post-irradiation. In contrast, the intensities of the bands were faint and did not significantly increase in LEC rat ells during 0-6 hr incubation after X-irradiation. Present results suggested that the radioresistant DNA synthesis in LEC rat cells is thought to be due to the abnormal G1 arrest following X-irradiation

  11. The Theobroma cacao B3 domain transcription factor TcLEC2 plays a duel role in control of embryo development and maturation.

    Science.gov (United States)

    Zhang, Yufan; Clemens, Adam; Maximova, Siela N; Guiltinan, Mark J

    2014-04-24

    The Arabidopsis thaliana LEC2 gene encodes a B3 domain transcription factor, which plays critical roles during both zygotic and somatic embryogenesis. LEC2 exerts significant impacts on determining embryogenic potential and various metabolic processes through a complicated genetic regulatory network. An ortholog of the Arabidopsis Leafy Cotyledon 2 gene (AtLEC2) was characterized in Theobroma cacao (TcLEC2). TcLEC2 encodes a B3 domain transcription factor preferentially expressed during early and late zygotic embryo development. The expression of TcLEC2 was higher in dedifferentiated cells competent for somatic embryogenesis (embryogenic calli), compared to non-embryogenic calli. Transient overexpression of TcLEC2 in immature zygotic embryos resulted in changes in gene expression profiles and fatty acid composition. Ectopic expression of TcLEC2 in cacao leaves changed the expression levels of several seed related genes. The overexpression of TcLEC2 in cacao explants greatly increased the frequency of regeneration of stably transformed somatic embryos. TcLEC2 overexpressing cotyledon explants exhibited a very high level of embryogenic competency and when cultured on hormone free medium, exhibited an iterative embryogenic chain-reaction. Our study revealed essential roles of TcLEC2 during both zygotic and somatic embryo development. Collectively, our evidence supports the conclusion that TcLEC2 is a functional ortholog of AtLEC2 and that it is involved in similar genetic regulatory networks during cacao somatic embryogenesis. To our knowledge, this is the first detailed report of the functional analysis of a LEC2 ortholog in a species other then Arabidopsis. TcLEC2 could potentially be used as a biomarker for the improvement of the SE process and screen for elite varieties in cacao germplasm.

  12. 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.

  13. Toward scalable parts families for predictable design of biological circuits.

    Science.gov (United States)

    Lucks, Julius B; Qi, Lei; Whitaker, Weston R; Arkin, Adam P

    2008-12-01

    Our current ability to engineer biological circuits is hindered by design cycles that are costly in terms of time and money, with constructs failing to operate as desired, or evolving away from the desired function once deployed. Synthetic biologists seek to understand biological design principles and use them to create technologies that increase the efficiency of the genetic engineering design cycle. Central to the approach is the creation of biological parts--encapsulated functions that can be composited together to create new pathways with predictable behaviors. We define five desirable characteristics of biological parts--independence, reliability, tunability, orthogonality and composability, and review studies of small natural and synthetic biological circuits that provide insights into each of these characteristics. We propose that the creation of appropriate sets of families of parts with these properties is a prerequisite for efficient, predictable engineering of new function in cells and will enable a large increase in the sophistication of genetic engineering applications.

  14. Angiogenenic effects of BpLec, a C-type lectin isolated from Bothrops pauloensis snake venom.

    Science.gov (United States)

    Castanheira, Letícia Eulalio; Lopes, Daiana Silva; Gimenes, Sarah Natalie Cirilo; Deconte, Simone Ramos; Ferreira, Bruno Antônio; Alves, Patricia Terra; Filho, Luiz Ricardo Goulart; Tomiosso, Tatiana Carla; Rodrigues, Renata Santos; Yoneyama, Kelly Aparecida Geraldo; Araújo, Fernanda de Assis; Rodrigues, Veridiana de Melo

    2017-09-01

    The present work reports the effects of a C-type lectin (BpLec) isolated from Bothrops pauloensis snake venom upon in vitro and in vivo angiogenesis models. Initially, we noted that BpLec was not cytotoxic to endothelial cells (tEnd) in doses up to 40μg/mL, but lower doses (2.5μg/mL, 5μg/mL, 10μg/mL and 20μg/mL) reduced tEnd cells adhesion to some extracellular matrix proteins and inhibited the in vitro vessel formation in Matrigel assay stimulated by bFGF. β-galactosides (d-lactose, N-acetyl-d-galactosamine and d-galactose) at 400mM reversed the effect of BpLec on tEnd cells adhesion, whereas d-galactose (400mM) partially reversed BpLec property of inhibiting vessel formation by tEnd cells in Matrigel. In vivo assays showed that BpLec increased hemoglobin content and capillary vessels number in polyether-polyurethane sponge discs subcutaneously implanted into dorsal skin mice. Additionally, BpLec also reduced collagen deposition and did not induce a pro-inflammatory response, as demonstrated by the decreased the secretion of some inflammatory cytokines, whereas myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) activities were not altered by BpLec. Taken together, our results indicate that BpLec might represent an interesting angiogenesis and inflammatory modulator that could also be used for searching possible therapeutic targets involved in these processes. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Data Integration and Mining for Synthetic Biology Design.

    Science.gov (United States)

    Mısırlı, Göksel; Hallinan, Jennifer; Pocock, Matthew; Lord, Phillip; McLaughlin, James Alastair; Sauro, Herbert; Wipat, Anil

    2016-10-21

    One aim of synthetic biologists is to create novel and predictable biological systems from simpler modular parts. This approach is currently hampered by a lack of well-defined and characterized parts and devices. However, there is a wealth of existing biological information, which can be used to identify and characterize biological parts, and their design constraints in the literature and numerous biological databases. However, this information is spread among these databases in many different formats. New computational approaches are required to make this information available in an integrated format that is more amenable to data mining. A tried and tested approach to this problem is to map disparate data sources into a single data set, with common syntax and semantics, to produce a data warehouse or knowledge base. Ontologies have been used extensively in the life sciences, providing this common syntax and semantics as a model for a given biological domain, in a fashion that is amenable to computational analysis and reasoning. Here, we present an ontology for applications in synthetic biology design, SyBiOnt, which facilitates the modeling of information about biological parts and their relationships. SyBiOnt was used to create the SyBiOntKB knowledge base, incorporating and building upon existing life sciences ontologies and standards. The reasoning capabilities of ontologies were then applied to automate the mining of biological parts from this knowledge base. We propose that this approach will be useful to speed up synthetic biology design and ultimately help facilitate the automation of the biological engineering life cycle.

  16. Development of the Biological Experimental Design Concept Inventory (BEDCI)

    Science.gov (United States)

    Deane, Thomas; Nomme, Kathy; Jeffery, Erica; Pollock, Carol; Birol, Gulnur

    2014-01-01

    Interest in student conception of experimentation inspired the development of a fully validated 14-question inventory on experimental design in biology (BEDCI) by following established best practices in concept inventory (CI) design. This CI can be used to diagnose specific examples of non-expert-like thinking in students and to evaluate the…

  17. Robust synthetic biology design: stochastic game theory approach.

    Science.gov (United States)

    Chen, Bor-Sen; Chang, Chia-Hung; Lee, Hsiao-Ching

    2009-07-15

    Synthetic biology is to engineer artificial biological systems to investigate natural biological phenomena and for a variety of applications. However, the development of synthetic gene networks is still difficult and most newly created gene networks are non-functioning due to uncertain initial conditions and disturbances of extra-cellular environments on the host cell. At present, how to design a robust synthetic gene network to work properly under these uncertain factors is the most important topic of synthetic biology. A robust regulation design is proposed for a stochastic synthetic gene network to achieve the prescribed steady states under these uncertain factors from the minimax regulation perspective. This minimax regulation design problem can be transformed to an equivalent stochastic game problem. Since it is not easy to solve the robust regulation design problem of synthetic gene networks by non-linear stochastic game method directly, the Takagi-Sugeno (T-S) fuzzy model is proposed to approximate the non-linear synthetic gene network via the linear matrix inequality (LMI) technique through the Robust Control Toolbox in Matlab. Finally, an in silico example is given to illustrate the design procedure and to confirm the efficiency and efficacy of the proposed robust gene design method. http://www.ee.nthu.edu.tw/bschen/SyntheticBioDesign_supplement.pdf.

  18. Predicting Translation Initiation Rates for Designing Synthetic Biology

    International Nuclear Information System (INIS)

    Reeve, Benjamin; Hargest, Thomas; Gilbert, Charlie; Ellis, Tom

    2014-01-01

    In synthetic biology, precise control over protein expression is required in order to construct functional biological systems. A core principle of the synthetic biology approach is a model-guided design and based on the biological understanding of the process, models of prokaryotic protein production have been described. Translation initiation rate is a rate-limiting step in protein production from mRNA and is dependent on the sequence of the 5′-untranslated region and the start of the coding sequence. Translation rate calculators are programs that estimate protein translation rates based on the sequence of these regions of an mRNA, and as protein expression is proportional to the rate of translation initiation, such calculators have been shown to give good approximations of protein expression levels. In this review, three currently available translation rate calculators developed for synthetic biology are considered, with limitations and possible future progress discussed.

  19. Design of the RFID for Storage of Biological Information

    OpenAIRE

    Sang-Hee Son; Seok-Man Kim; Yu-Lee Choi; Kyoung-Rok Cho

    2009-01-01

    Recent advances in RFID (radio frequency identification) technology promises to create a wireless circuitry capable of interfacing with biological systems for acquisition, identification and processing of biological data based on radio frequency interaction. Thus, the RFID tag can be attached not only to consumer products and form part of the supply chain, but also to animals, plants and in particular human body. This paper describes the strategy for the design of a novel RFID tag, which stor...

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

    Science.gov (United States)

    Otero-Muras, Irene; Banga, Julio R

    2017-07-21

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

  1. 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.

  2. How Biology Teachers Can Respond to Intelligent Design

    Science.gov (United States)

    Mackenzie, Jim

    2010-01-01

    Teachers of biology and related subjects are increasingly meeting objections from students and their parents to the teaching of evolution and the exclusion of what is called the theory of Intelligent Design. This paper attempts to draw together arguments and evidence which may be used by such teachers. Four lessons are drawn from the 1982…

  3. cld and lec23 are disparate mutations that affect maturation of lipoprotein lipase in the endoplasmic reticulum.

    Science.gov (United States)

    Briquet-Laugier, V; Ben-Zeev, O; White, A; Doolittle, M H

    1999-11-01

    The mutations cld (combined lipase deficiency) and lec23 disrupt in a similar manner the expression of lipoprotein lipase (LPL). Whereas cld affects an unknown gene, lec23 abolishes the activity of alpha-glucosidase I, an enzyme essential for proper folding and assembly of nascent glycoproteins. The hypothesis that cld, like lec23, affects the folding/assembly of nascent LPL was confirmed by showing that in cell lines homozygous for these mutations (Cld and Lec23, respectively), the majority of LPL was inactive, displayed heterogeneous aggregation, and had a decreased affinity for heparin. While inactive LPL was retained in the ER, a small amount of LPL that had attained a native conformation was transported through the Golgi and secreted. Thus, Cld and Lec23 cells recognized and retained the majority of LPL as misfolded, maintaining the standard of quality control. Examination of candidate factors affecting protein maturation, such as glucose addition and trimming, proteins involved in lectin chaperone cycling, and other abundant ER chaperones, revealed that calnexin levels were dramatically reduced in livers from cld/cld mice; this finding was also confirmed in Cld cells. We conclude that cld may affect components in the ER, such as calnexin, that play a role in protein maturation. Whether the reduced calnexin levels per se contribute to the LPL deficiency awaits confirmation.

  4. Design control considerations for biologic-device combination products.

    Science.gov (United States)

    Anderson, Dave; Liu, Roger; Anand Subramony, J; Cammack, Jon

    2017-03-01

    Combination products are therapeutic and diagnostic medical products that combine drugs, devices, and/or biological products with one another. Historically, biologics development involved identifying efficacious doses administered to patients intravenously or perhaps by a syringe. Until fairly recently, there has been limited focus on developing an accompanying medical device, such as a prefilled syringe or auto-injector, to enable easy and more efficient delivery. For the last several years, and looking forward, where there may be little to distinguish biologics medicines with relatively similar efficacy profiles, the biotechnology market is beginning to differentiate products by patient-focused, biologic-device based combination products. As innovative as biologic-device combination products are, they can pose considerable development, regulatory, and commercialization challenges due to unique physicochemical properties and special clinical considerations (e.g., dosing volumes, frequency, co-medications, etc.) of the biologic medicine. A biologic-device combination product is a marriage between two partners with "cultural differences," so to speak. There are clear differences in the development, review, and commercialization processes of the biologic and the device. When these two cultures come together in a combination product, developers and reviewers must find ways to address the design controls and risk management processes of both the biologic and device, and knit them into a single entity with supporting product approval documentation. Moreover, digital medicine and connected health trends are pushing the boundaries of combination product development and regulations even further. Despite an admirable cooperation between industry and FDA in recent years, unique product configurations and design features have resulted in review challenges. These challenges have prompted agency reviewers to modernize consultation processes, while at the same time, promoting

  5. Design of the RFID for Storage of Biological Information

    Directory of Open Access Journals (Sweden)

    Sang-Hee Son

    2009-02-01

    Full Text Available Recent advances in RFID (radio frequency identification technology promises to create a wireless circuitry capable of interfacing with biological systems for acquisition, identification and processing of biological data based on radio frequency interaction. Thus, the RFID tag can be attached not only to consumer products and form part of the supply chain, but also to animals, plants and in particular human body. This paper describes the strategy for the design of a novel RFID tag, which stores vital biological information such as body temperature and blood pressure and heartbeat in accordance with the EPC global Class-1 standard. Biological data is obtained from a sensor technology that is based on resistance deviation-to-pulse width converter. The integrated chip consists of an analog front end, command interpreter, collision avoidance block, data storage, sensors, and interface circuitry. The system is capable of supporting heartbeats in the range of 40~200 beats per a minute and blood pressure 0~300mmHg. The proposed system employs collision free algorithm that supports access to single tag within a multiple tag environment. The approach facilitates intelligent management of patients in hospitals as part of an integrated healthcare management system.

  6. 47 CFR 52.23 - Deployment of long-term database methods for number portability by LECs.

    Science.gov (United States)

    2010-10-01

    ... number portability by LECs. 52.23 Section 52.23 Telecommunication FEDERAL COMMUNICATIONS COMMISSION...) Does not require end users to change their telecommunications numbers; (4) Does not result in... degradation in service quality or network reliability when customers switch carriers; (6) Does not result in a...

  7. ODMR of shallow donors in Zn-doped LEC-grown InP

    International Nuclear Information System (INIS)

    Trombetta, J.M.; Kennedy, T.A.

    1990-01-01

    ODMR spectra observed while monitoring the shallow donor-shallow acceptor pair emission in Zn-doped LEC-grown InP display strong features in the region near the conduction electron value of g = 1.20. In addition to a previously observed narrow line, the authors observe a much broader resonance which dominates at low photoexcitation intensity. This broader line is interpreted as the unresolved exchange split resonances of electrons bound to residual shallow donors. The exchange broadening arises from interaction with nearby paramagnetic centers. Both resonances result in a decrease in the shallow-donor-to shallow-acceptor radiative recombination and give evidence for pair recombination processes which compete with this emission

  8. Artificial heartbeat: design and fabrication of a biologically inspired pump

    International Nuclear Information System (INIS)

    Walters, Peter; Stephenson, Robert; Lewis, Amy; Stinchcombe, Andrew; Ieropoulos, Ioannis

    2013-01-01

    We present a biologically inspired actuator exhibiting a novel pumping action. The design of the ‘artificial heartbeat’ actuator is inspired by physical principles derived from the structure and function of the human heart. The actuator employs NiTi artificial muscles and is powered by electrical energy generated by microbial fuel cells (MFCs). We describe the design and fabrication of the actuator and report the results of tests conducted to characterize its performance. This is the first artificial muscle-driven pump to be powered by MFCs fed on human urine. Results are presented in terms of the peak pumping pressure generated by the actuator, as well as for the volume of fluid transferred, when the actuator was powered by energy stored in a capacitor bank, which was charged by 24 MFCs fed on urine. The results demonstrate the potential for the artificial heartbeat actuator to be employed as a fluid circulation pump in future generations of MFC-powered robots (‘EcoBots’) that extract energy from organic waste. We also envisage that the actuator could in the future form part of a bio-robotic artwork or ‘bio-automaton’ that could help increase public awareness of research in robotics, bio-energy and biologically inspired design. (paper)

  9. A systematic design method for robust synthetic biology to satisfy design specifications.

    Science.gov (United States)

    Chen, Bor-Sen; Wu, Chih-Hung

    2009-06-30

    Synthetic biology is foreseen to have important applications in biotechnology and medicine, and is expected to contribute significantly to a better understanding of the functioning of complex biological systems. However, the development of synthetic gene networks is still difficult and most newly created gene networks are non-functioning due to intrinsic parameter uncertainties, external disturbances and functional variations of intra- and extra-cellular environments. The design method for a robust synthetic gene network that works properly in a host cell under these intrinsic parameter uncertainties and external disturbances is the most important topic in synthetic biology. In this study, we propose a stochastic model that includes parameter fluctuations and external disturbances to mimic the dynamic behaviors of a synthetic gene network in the host cell. Then, based on this stochastic model, four design specifications are introduced to guarantee that a synthetic gene network can achieve its desired steady state behavior in spite of parameter fluctuations, external disturbances and functional variations in the host cell. We propose a systematic method to select a set of appropriate design parameters for a synthetic gene network that will satisfy these design specifications so that the intrinsic parameter fluctuations can be tolerated, the external disturbances can be efficiently filtered, and most importantly, the desired steady states can be achieved. Thus the synthetic gene network can work properly in a host cell under intrinsic parameter uncertainties, external disturbances and functional variations. Finally, a design procedure for the robust synthetic gene network is developed and a design example is given in silico to confirm the performance of the proposed method. Based on four design specifications, a systematic design procedure is developed for designers to engineer a robust synthetic biology network that can achieve its desired steady state behavior

  10. Removal design report for the 108-F Biological Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-09-01

    Most of the 100-F facilities were deactivated with the reactor and have since been demolished. Of the dozen or so reactor-related structures, only the 105-F Reactor Building and the 108-F Biology Laboratory remain standing today. The 108-F Biology Laboratory was intended to be used as a facility for the mixing and addition of chemicals used in the treatment of the reactor cooling water. Shortly after F Reactor began operation, it was determined that the facility was not needed for this purpose. In 1949, the building was converted for use as a biological laboratory. In 1962, the lab was expanded by adding a three-story annex to the original four-story structure. The resulting lab had a floor area of approximately 2,883 m{sup 2} (main building and annex) that operated until 1973. The building contained 47 laboratories, a number of small offices, a conference room, administrative section, lunch and locker rooms, and a heavily shielded, high-energy exposure cell. The purpose of this removal design report is to establish the methods of decontamination and decommissioning and the supporting functions associated with facility removal and disposal.

  11. Removal design report for the 108-F Biological Laboratory

    International Nuclear Information System (INIS)

    1997-09-01

    Most of the 100-F facilities were deactivated with the reactor and have since been demolished. Of the dozen or so reactor-related structures, only the 105-F Reactor Building and the 108-F Biology Laboratory remain standing today. The 108-F Biology Laboratory was intended to be used as a facility for the mixing and addition of chemicals used in the treatment of the reactor cooling water. Shortly after F Reactor began operation, it was determined that the facility was not needed for this purpose. In 1949, the building was converted for use as a biological laboratory. In 1962, the lab was expanded by adding a three-story annex to the original four-story structure. The resulting lab had a floor area of approximately 2,883 m 2 (main building and annex) that operated until 1973. The building contained 47 laboratories, a number of small offices, a conference room, administrative section, lunch and locker rooms, and a heavily shielded, high-energy exposure cell. The purpose of this removal design report is to establish the methods of decontamination and decommissioning and the supporting functions associated with facility removal and disposal

  12. Biosimilars design and analysis of follow-on biologics

    CERN Document Server

    2013-01-01

    "This book extensively covers both statistical and regulatory considerations from design to analysis of biosimilarity. … it is well presented and comprehensively covers fundamental issues and some of the newly developed methods for biosimilarity studies. The book is very balanced between scientific aspects and regulatory requirements. In addition, the reference lists give readers helpful information. … a valuable resource for anyone interested and involved in biosimilarity studies."-Biometrics, September 2014"[Professor] Chow's book Biosimilars: Design and Analysis of Follow-On Biologics … is the first book ever written on this topic. I commend Professor Chow for his effort to introduce the topic … Overall, this is a worthwhile reference book for statisticians interested in understanding biosimilar product development and evaluation." -Yi Tsong, PhD, Center for Drug Evaluation and Research, US Food and Drug Administration, USA, in Journal of Biopharmaceutical Statistics>.

  13. Design of fluidized-bed, biological denitrification systems

    International Nuclear Information System (INIS)

    Patton, B.D.; Hancher, C.W.; Pitt, W.W.; Walker, J.F.

    1982-01-01

    Many commercial processes yield nitrate-containing wastewaters that are being discharged to the environment because traditional recovery or disposal methods are economically unacceptable. The anticipated discharge limits (i.e., 10 to 20 g (NO 3 - )/m 3 ) being considered by many states will not allow continued release of these wastewaters. The new discharge standards can be met economically by use of the fluidizied-bed, biological denitrification process. Research and development studies were conducted with 0.05-, 0.10-, 0.20-, and 0.50-m-diam fluidized-bed bioreactor systems. Feed nitrate concentrations were in the 0 to 10,000 g (NO 3 - )/m 3 range. Using the data from these studies, rate expressions were developed for the destruction of nitrate as a function of nitrate concentration. Methods were also developed for sizing bioreactors and biomass control systems. The sizing methods for fluidized-bed denitrification systems are described, and support systems such as sampling and analysis, instrumentation and controls, utilities, and bacteria storage are discussed. Operation of the process is also briefly discussed to aid the designer. Using the methods presented in this report, fluidized-bed, biological denitrification systems can be designed to treat nitrate wastewater streams

  14. A high frequency of induction of chromosome aberrations in the bone marrow cells of LEC strain rats by X-irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Okui, Toyo (Hokkaido Inst. of Public Health, Sapporo (Japan)); Hayashi, Masanobu; Watanabe, Tomomasa; Namioka, Shigeo (Dept. of Lab. Animal Science, Hokkaido Univ., Sapporo (Japan)); Endoh, Daiji; Sato, Fumiaki (Dept. of Radiation Biology, Faculty of Veterinary Medicine, Hokkaido Univ., Sapporo (Japan)); Kasai, Noriyuki (Inst. for Animal Experimentation, Hokkaido Univ., Sapporo (Japan))

    1994-08-01

    LEC strain rats, which have been known to develop hereditarily spontaneous fulminant hepatitis 4 to 5 months after birth, are highly sensitive to whole-body X-irradiation when compared to WKAH strain rats. The present results showed that the frequencies of all types of chromosome aberrations induced by X-irradiation in the bone marrow cells of LEC rats were approximately 2- to 3-fold higher than those of WKAH rats, though no significant difference was observed in the frequency of spontaneous chromosome aberrations between LEC and WKAH rats.

  15. Phosphorus-hydrogen complexes in LEC-grown InP

    International Nuclear Information System (INIS)

    Ulrici, W.; Kwasniewski, A.; Czupalla, M.; Neubert, M.

    2005-01-01

    In LEC-grown InP, about 30 sharp vibrational absorption lines are measured in the frequency region 2200 to 2350 cm -1 . All these lines are due to phosphorus-hydrogen stretching modes. Experiments on InP containing both hydrogen and deuterium finally proved that the line at 2202.4 cm -1 is due to a single hydrogen atom bonded to P in an indium vacancy (V In ) and that the line at 2315.6 cm -1 is due to the complex of four P-H bonds in an V In . In InP:H:D, this V In H 4 complex gives rise to six vibrational lines in the region of P-H modes and six lines in the region of P-D modes because of the five different types of V In H n D m complexes. The measured frequencies of these 12 lines are in excellent agreement with those obtained from ab initio calculations reported in the literature. Additional P-H complexes are discussed. (copyright 2005 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  16. Phosphorus-hydrogen complexes in LEC-grown InP

    Energy Technology Data Exchange (ETDEWEB)

    Ulrici, W. [Paul-Drude-Institut fuer Festkoerperelektronik, Hausvogteiplatz 5-7, 10117 Berlin (Germany); Kwasniewski, A.; Czupalla, M.; Neubert, M. [Institut fuer Kristallzuechtung, Max-Born-Str. 2, 12489 Berlin (Germany)

    2005-03-01

    In LEC-grown InP, about 30 sharp vibrational absorption lines are measured in the frequency region 2200 to 2350 cm{sup -1}. All these lines are due to phosphorus-hydrogen stretching modes. Experiments on InP containing both hydrogen and deuterium finally proved that the line at 2202.4 cm{sup -1} is due to a single hydrogen atom bonded to P in an indium vacancy (V{sub In}) and that the line at 2315.6 cm{sup -1} is due to the complex of four P-H bonds in an V{sub In}. In InP:H:D, this V{sub In}H{sub 4} complex gives rise to six vibrational lines in the region of P-H modes and six lines in the region of P-D modes because of the five different types of V{sub In}H{sub n}D{sub m} complexes. The measured frequencies of these 12 lines are in excellent agreement with those obtained from ab initio calculations reported in the literature. Additional P-H complexes are discussed. (copyright 2005 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  17. Designing and Implementing a New Advanced Level Biology Course

    Science.gov (United States)

    Hall, Angela; Reiss, Michael J.; Rowell, Cathy; Scott, Anne

    2003-01-01

    Salters-Nuffield Advanced Biology is a new advanced level biology course, piloted from September 2002 in England with around 1200 students. This paper discusses the reasons for developing a new advanced biology course at this time, the philosophy of the project and how the materials are being written and the specification devised. The aim of the…

  18. Expression of ZmLEC1 and ZmWRI1 increases seed oil production in maize.

    Science.gov (United States)

    Shen, Bo; Allen, William B; Zheng, Peizhong; Li, Changjiang; Glassman, Kimberly; Ranch, Jerry; Nubel, Douglas; Tarczynski, Mitchell C

    2010-07-01

    Increasing seed oil production is a major goal for global agriculture to meet the strong demand for oil consumption by humans and for biodiesel production. Previous studies to increase oil synthesis in plants have focused mainly on manipulation of oil pathway genes. As an alternative to single-enzyme approaches, transcription factors provide an attractive solution for altering complex traits, with the caveat that transcription factors may face the challenge of undesirable pleiotropic effects. Here, we report that overexpression of maize (Zea mays) LEAFY COTYLEDON1 (ZmLEC1) increases seed oil by as much as 48% but reduces seed germination and leaf growth in maize. To uncouple oil increase from the undesirable agronomic traits, we identified a LEC1 downstream transcription factor, maize WRINKLED1 (ZmWRI1). Overexpression of ZmWRI1 results in an oil increase similar to overexpression of ZmLEC1 without affecting germination, seedling growth, or grain yield. These results emphasize the importance of field testing for developing a commercial high-oil product and highlight ZmWRI1 as a promising target for increasing oil production in crops.

  19. The Arabidopsis lectin receptor kinase LecRK-V.5 represses stomatal immunity induced by Pseudomonas syringae pv. tomato DC3000.

    Directory of Open Access Journals (Sweden)

    Marie Desclos-Theveniau

    2012-02-01

    Full Text Available Stomata play an important role in plant innate immunity by limiting pathogen entry into leaves but molecular mechanisms regulating stomatal closure upon pathogen perception are not well understood. Here we show that the Arabidopsis thaliana L-type lectin receptor kinase-V.5 (LecRK-V.5 negatively regulates stomatal immunity. Loss of LecRK-V.5 function increased resistance to surface inoculation with virulent bacteria Pseudomonas syringae pv tomato DC3000. Levels of resistance were not affected after infiltration-inoculation, suggesting that LecRK-V.5 functions at an early defense stage. By contrast, lines overexpressing LecRK-V.5 were more susceptible to Pst DC3000. Enhanced resistance in lecrk-V.5 mutants was correlated with constitutive stomatal closure, while increased susceptibility phenotypes in overexpression lines were associated with early stomatal reopening. Lines overexpressing LecRK-V.5 also demonstrated a defective stomatal closure after pathogen-associated molecular pattern (PAMP treatments. LecRK-V.5 is rapidly expressed in stomatal guard cells after bacterial inoculation or treatment with the bacterial PAMP flagellin. In addition, lecrk-V.5 mutants guard cells exhibited constitutive accumulation of reactive oxygen species (ROS and inhibition of ROS production opened stomata of lecrk-V.5. LecRK-V.5 is also shown to interfere with abscisic acid-mediated stomatal closure signaling upstream of ROS production. These results provide genetic evidences that LecRK-V.5 negatively regulates stomatal immunity upstream of ROS biosynthesis. Our data reveal that plants have evolved mechanisms to reverse bacteria-mediated stomatal closure to prevent long-term effect on CO(2 uptake and photosynthesis.

  20. Designing and implementing a new advanced level biology course.

    OpenAIRE

    Hall, Angela; Reiss, Michael; Rowell, Cathy; Scott, C.; Scott, Anne

    2003-01-01

    Salters-Nuffield Advanced Biology is a new advanced level biology course currently being piloted from September 2002 in England with around 1200 students. This paper discusses the reasons for developing a new advanced biology course at this time, the philosophy of the project and how the materials are being written and the specification devised. The aim of the project is to provide an up-to-date course that interests students, is considered appropriate by teachers and other professionals in b...

  1. A Hierarchical Biology Concept Framework: A Tool for Course Design

    OpenAIRE

    Khodor, Julia; Halme, Dina Gould; Walker, Graham C.

    2004-01-01

    A typical undergraduate biology curriculum covers a very large number of concepts and details. We describe the development of a Biology Concept Framework (BCF) as a possible way to organize this material to enhance teaching and learning. Our BCF is hierarchical, places details in context, nests related concepts, and articulates concepts that are inherently obvious to experts but often difficult ...

  2. The Arabidopsis thaliana lectin receptor kinase LecRK-I.9 is required for full resistance to Pseudomonas syringae and affects jasmonate signalling.

    Science.gov (United States)

    Balagué, Claudine; Gouget, Anne; Bouchez, Olivier; Souriac, Camille; Haget, Nathalie; Boutet-Mercey, Stéphanie; Govers, Francine; Roby, Dominique; Canut, Hervé

    2017-09-01

    On microbial attack, plants can detect invaders and activate plant innate immunity. For the detection of pathogen molecules or cell wall damage, plants employ receptors that trigger the activation of defence responses. Cell surface proteins that belong to large families of lectin receptor kinases are candidates to function as immune receptors. Here, the function of LecRK-I.9 (At5g60300), a legume-type lectin receptor kinase involved in cell wall-plasma membrane contacts and in extracellular ATP (eATP) perception, was studied through biochemical, gene expression and reverse genetics approaches. In Arabidopsis thaliana, LecRK-I.9 expression is rapidly, highly and locally induced on inoculation with avirulent strains of Pseudomonas syringae pv. tomato (Pst). Two allelic lecrk-I.9 knock-out mutants showed decreased resistance to Pst. Conversely, over-expression of LecRK-I.9 led to increased resistance to Pst. The analysis of defence gene expression suggests an alteration of both the salicylic acid (SA) and jasmonic acid (JA) signalling pathways. In particular, LecRK-I.9 expression during plant-pathogen interaction was dependent on COI1 (CORONATINE INSENSITIVE 1) and JAR1 (JASMONATE RESISTANT 1) components, and JA-responsive transcription factors (TFs) showed altered levels of expression in plants over-expressing LecRK-I.9. A similar misregulation of these TFs was obtained by JA treatment. This study identified LecRK-I.9 as necessary for full resistance to Pst and demonstrated its involvement in the control of defence against pathogens through a regulation of JA signalling components. The role of LecRK-I.9 is discussed with regard to the potential molecular mechanisms linking JA signalling to cell wall damage and/or eATP perception. © 2016 BSPP AND JOHN WILEY & SONS LTD.

  3. AC Calorimetric Design for Dynamic of Biological Materials

    OpenAIRE

    Shigeo Imaizumi

    2006-01-01

    We developed a new AC calorimeter for the measurement of dynamic specific heat capacity in liquids, including aqueous suspensions of biological materials. This method has several advantages. The first is that a high-resolution measurement of heat capacity, inmillidegrees, can be performed as a function of temperature, even with a very small sample. Therefore, AC calorimeter is a powerful tool to study critical behavior a tphase transition in biological materials. The second advantage is that ...

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

    Science.gov (United States)

    Young, Eric; Alper, Hal

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Eric Young

    2010-01-01

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

  6. Synthetic biology: tools to design, build, and optimize cellular processes.

    Science.gov (United States)

    Young, Eric; Alper, Hal

    2010-01-01

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

  7. Design, Synthesis, and Biological Evaluation of Isothiosemicarbazones with Antimycobacterial Activity

    Czech Academy of Sciences Publication Activity Database

    Novotná, E.; Waisser, K.; Kuneš, J.; Palát, K.; Skálová, L.; Szotáková, B.; Buchta, V.; Stolaříková, J.; Ulmann, V.; Pávová, Marcela; Weber, Jan; Komrsková, J.; Hašková, P.; Vokřál, I.; Wsól, V.

    2017-01-01

    Roč. 350, č. 8 (2017), č. článku e1700020. ISSN 0365-6233 Institutional support: RVO:61388963 Keywords : biological activity * cytotoxicity * isocitrate lyase * isothiosemicarbazone * tuberculosis Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 1.994, year: 2016

  8. Design of Functional Polyesters for Electronic and Biological Applications

    OpenAIRE

    Nelson, Ashley Marie

    2015-01-01

    Melt polymerization and novel monomers enabled the synthesis of polyesters for electronic and biological applications. Inspiration from nature and a passion for environmental preservation instigated an emphasis on the incorporation of renewable resources into polymeric materials. Critical analysis of current research surrounding bisphenol-A replacements and ioncontaining segmented polyurethanes aided in identifying benchmark polymers, including limitations, challenges, and future needs. Struc...

  9. Procedure for developing biological input for the design, location, or modification of water-intake structures

    Energy Technology Data Exchange (ETDEWEB)

    Neitzel, D.A.; McKenzie, D.H.

    1981-12-01

    To minimize adverse impact on aquatic ecosystems resulting from the operation of water intake structures, design engineers must have relevant information on the behavior, physiology and ecology of local fish and shellfish. Identification of stimulus/response relationships and the environmental factors that influence them is the first step in incorporating biological information in the design, location or modification of water intake structures. A procedure is presented in this document for providing biological input to engineers who are designing, locating or modifying a water intake structure. The authors discuss sources of stimuli at water intakes, historical approaches in assessing potential/actual impact and review biological information needed for intake design.

  10. Synthetic Biology: Engineering, Evolution and Design (SEED) Conference 2015

    Science.gov (United States)

    2015-12-01

    yield stability. Transgenic approach plays an important role in crop improvement. Currently, transgenes are randomly inserted into maize genome...Improve Microbial Biofuel Production - Mary Dunlop, University of Vermont 2:30-3:00 PM Targeted Integration of Genes into the Maize Genome Facilitated...highlights gaps in the present understanding of M13 biology. Understanding the subtleties of regulation will be important for maximally ex- ploiting the

  11. 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).

  12. Purification and characterization of Cc-Lec, C-type lactose-binding lectin: A platelet aggregation and blood-clotting inhibitor from Cerastes cerastes venom.

    Science.gov (United States)

    Samah, Saoud; Fatah, Chérifi; Jean-Marc, Berjeaud; Safia, Kellou-Taîri; Fatima, Laraba-Djebari

    2017-09-01

    In this study, we reported for the first time the biochemical and structural characterization of Cc-Lec, a C-type lectin purified from Cerastes cerastes venom by affinity chromatography. This lectin was homogeneous by SDS-PAGE, and was shown to be a 34 271.59Da polypeptide by Electrospray mass spectrometry MS-ES-TOF. Its identified sequence of 160 amino acids corresponding to one subunit, revealed a high identity with other related proteins. Cc-Lec modeled 3D structure appeared as homodimer cross-linked by one disulfide bridge. Cc-Lec exhibited a calcium dependent hemagglutinating activity against human group O erythrocytes. Cc-Lec inhibited platelet aggregation induced by ADP, arachidonic acid or fibrinogen suggesting its interaction with their specific receptors namely P2Y1 and/or P2Y12, GPIIb/IIIa and TPα respectively. Cc-Lec was not lethal for mice until 10mg/kg administered by i.p. route. The lectin displayed a lasting anticoagulation on mice plasma even two days post-injection. This anticoagulation seems to be related to its interaction with coagulation factors Xa and IXa. Therefore, Cc-Lec prevented FXa amidolytic activity with Km=4.3310 -4 μg/mL and ki=14.4μg/mL. It seems to interact with these targets through CRD domain which could make it a good target as a pharmacological promising molecule in thrombosis diagnosis and therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Disentangling the Role of the MEC and LEC in the Processing of Spatial and Non-Spatial Information: Contribution of Lesion Studies

    Directory of Open Access Journals (Sweden)

    Etienne Save

    2017-10-01

    Full Text Available It is now widely accepted that the entorhinal cortex (EC plays a pivotal role in the processing of spatial information and episodic memory. The EC is segregated into two sub-regions, the medial EC (MEC and the lateral EC (LEC but a comprehensive understanding of their roles across multiple behavioral contexts remains unclear. Considering that it is still useful to investigate the impact of lesions of EC on behavior, we review the contribution of lesion approach to our knowledge of EC functions. We show that the MEC and LEC play different roles in the processing of spatial and non-spatial information. The MEC is necessary to the use of distal but not proximal landmarks during navigation and is crucial for path integration, in particular integration of linear movements. Consistent with predominant hypothesis, the LEC is important for combining the spatial and non-spatial aspects of the environment. However, object exploration studies suggest that the functional segregation between the MEC and the LEC is not as clearly delineated and is dependent on environmental and behavioral factors. Manipulation of environmental complexity and therefore of cognitive demand shows that the MEC and the LEC are not strictly necessary to the processing of spatial and non-spatial information. In addition we suggest that the involvement of these sub-regions can depend on the kind of behavior, i.e., navigation or exploration, exhibited by the animals. Thus, the MEC and the LEC work in a flexible manner to integrate the “what” and “where” information in episodic memory upstream the hippocampus.

  14. Comparison between regenerative organic Rankine cycle (RORC) and basic organic Rankine cycle (BORC) based on thermoeconomic multi-objective optimization considering exergy efficiency and levelized energy cost (LEC)

    International Nuclear Information System (INIS)

    Feng, Yongqiang; Zhang, Yaning; Li, Bingxi; Yang, Jinfu; Shi, Yang

    2015-01-01

    Highlights: • The thermoeconomic comparison of regenerative RORC and BORC is investigated. • The Pareto frontier solution with bi-objective compares with the corresponding single-objective solutions. • The three-objective optimization of the RORC and BORC is studied. • The RORC owns 8.1% higher exergy efficiency and 21.1% more LEC than the BORC under the Pareto-optimal solution. - Abstract: Based on the thermoeconomic multi-objective optimization by using non-dominated sorting genetic algorithm (NSGA-II), considering both thermodynamic performance and economic factors, the thermoeconomic comparison of regenerative organic Rankine cycles (RORC) and basic organic Rankine cycles (BORC) are investigated. The effects of five key parameters including evaporator outlet temperature, condenser temperature, degree of superheat, pinch point temperature difference and degree of supercooling on the exergy efficiency and levelized energy cost (LEC) are examined. Meanwhile, the Pareto frontier solution with bi-objective for maximizing exergy efficiency and minimizing LEC is obtained and compared with the corresponding single-objective solutions. Research demonstrates that there is a significant negative correlation between thermodynamic performance and economic factors. And the optimum exergy efficiency and LEC for the Pareto-optimal solution of the RORC are 55.97% and 0.142 $/kW h, respectively, which are 8.1% higher exergy efficiency and 21.1% more LEC than that of the BORC under considered condition. Highest exergy and thermal efficiencies are accompanied with lowest net power output and worst economic performance. Furthermore, taking the net power output into account, detailed investigation on the three-objective optimization for maximizing exergy efficiency, maximizing net power output and minimizing LEC is discussed

  15. The design of trickling biological periwinkle shells filter for closed ...

    African Journals Online (AJOL)

    ... and economics of biofilter in reirculating aquaculture systems using local material ... The system with the designed biofilter served as the treatment system, while the ... The selected system recirculation rate was 10 times per hour, while the ...

  16. Novel Carbonyl Analogs of Tamoxifen: Design, Synthesis, and Biological Evaluation

    Directory of Open Access Journals (Sweden)

    Konstantinos M. Kasiotis

    2017-09-01

    Full Text Available Aim of this work was to provide tamoxifen analogs with enhanced estrogen receptor (ER binding affinity. Hence, several derivatives were prepared using an efficient triarylethylenes synthetic protocol. The novel compounds bioactivity was evaluated through the determination of their receptor binding affinity and their agonist/antagonist activity against breast cancer tissue using a MCF-7 cell-based assay. Phenyl esters 6a,b and 8a,b exhibited binding affinity to both ERα and ERβ higher than 4-hydroxytamoxifen while compounds 13 and 14 have shown cellular antiestrogenic activity similar to 4-hydroxytamoxifen and the known ER inhibitor ICI182,780. Theoretical calculations and molecular modeling were applied to investigate, support and explain the biological profile of the new compounds. The relevant data indicated an agreement between calculations and demonstrated biological activity allowing to extract useful structure-activity relationships. Results herein underline that modifications of tamoxifen structure still provide molecules with substantial activity, as portrayed in the inhibition of MCF-7 cells proliferation.

  17. Novel Carbonyl Analogues of Tamoxifen: Design, Synthesis, and Biological Evaluation

    Science.gov (United States)

    Kasiotis, Konstantinos M.; Lambrinidis, George; Fokialakis, Nikolas; Tzanetou, Evangelia N.; Mikros, Emmanuel; Haroutounian, Serkos A.

    2017-09-01

    Aim of this work was to provide tamoxifen analogues with enhanced estrogen receptor binding affinity. Hence, several derivatives were prepared using an efficient triarylethylenes synthetic protocol. The novel compounds bioactivity was evaluated through the determination of their receptor binding affinity and their agonist/antagonist activity against breast cancer tissue using a MCF-7 cell-based assay. Phenyl esters 6a,b and 8a,b exhibited binding affinity to both ERα and ERβ higher than 4-hydroxytamoxifen while compounds 13 and 14 have shown cellular antiestrogenic activity similar to 4-hydroxytamoxifen and the known estrogen receptor inhibitor ICI182,780. Theoretical calculations and molecular modelling were applied to investigate, support and explain the biological profile of the new compounds. The relevant data indicated an agreement between calculations and demonstrated biological activity allowing to extract useful structure-activity relationships. Results herein underline that modifications of tamoxifen structure still provide molecules with substantial activity, as portrayed in the inhibition of MCF-7 cells proliferation.

  18. Computer-aided design of biological circuits using TinkerCell.

    Science.gov (United States)

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

    2010-01-01

    Synthetic biology is an engineering discipline that builds on modeling practices from systems biology and wet-lab techniques from genetic engineering. As synthetic biology advances, efficient procedures will be developed that will allow a synthetic biologist to design, analyze, and build biological networks. In this idealized pipeline, computer-aided design (CAD) is a necessary component. The role of a CAD application would be to allow efficient transition from a general design to a final product. TinkerCell is a design tool for serving this purpose in synthetic biology. In TinkerCell, users build biological networks using biological parts and modules. The network can be analyzed using one of several functions provided by TinkerCell or custom programs from third-party sources. Since best practices for modeling and constructing synthetic biology networks have not yet been established, TinkerCell is designed as a flexible and extensible application that can adjust itself to changes in the field. © 2010 Landes Bioscience

  19. 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...

  20. Biological shield design for a 10 MeV Rhodotron

    International Nuclear Information System (INIS)

    Khalafi, H.; Ghane, A.; Safaei Arshi, S.; Tabakh, F.

    2012-01-01

    Highlights: ► We evaluate the produced radiations of the Rhodotron-TT200 and their attenuation to the permitted level. ► We apply analytical calculations to determine the shield material and thickness. ► We simulate the Rhodotron accelerator and its shielding using MCNPX code to make sure of results accuracy. -- Abstract: Radiation field of the Rhodotron-TT200 electron accelerator is determined in this study. Regarding the interactions of electron with matter, the produced radiations and their attenuation to the permitted level (i.e. 0.01 mrem/h) are evaluated and calculated. For this purpose analytical calculations are applied to determine the biological shield material and thickness. In order to make sure of results accuracy, Rhodotron accelerator and its shielding are simulated using MCNPX code and the results of analytical calculations and MCNPX code are compared with the experimental ones.

  1. Design synthesis and biological evaluation of 2-methylphenyl semicarbazone derivatives

    Directory of Open Access Journals (Sweden)

    Manmohan Singhal

    2011-03-01

    Full Text Available We have used pharmacophore hybridization technique of drug design and designed a pharmacophore model 2-methylphenylsemicarbazone which is having hydrogen acceptor site, hydrogen donor site, lipophilic site etc using ligandscout-2.02 software. A series of 2-methylphenyl-semicarbazone was synthesized and evaluated for their antipyretic activity using boiled cow milk induced pyrexia in rabbits. Compound 11 was the most active compound. The possible metabolites of some selected synthesized chalconesemicarbazones were predicted by computational method using Pallas version-3.1 ADME-Tox prediction software. The major pathway of metabolism was found to be p-hydroxylation and amide hydrolysis.

  2. Programming biological operating systems: genome design, assembly and activation.

    Science.gov (United States)

    Gibson, Daniel G

    2014-05-01

    The DNA technologies developed over the past 20 years for reading and writing the genetic code converged when the first synthetic cell was created 4 years ago. An outcome of this work has been an extraordinary set of tools for synthesizing, assembling, engineering and transplanting whole bacterial genomes. Technical progress, options and applications for bacterial genome design, assembly and activation are discussed.

  3. Molecular design, synthesis and evaluation of chemical biology tools

    NARCIS (Netherlands)

    Hoogenboom, Jorin

    2017-01-01

    Chapter 1 provides a perspective of synthetic organic chemistry as a discipline involved in the design, synthesis and evaluation of complex molecules. The reader is introduced with a brief history of synthetic organic chemistry, all the while dealing with different aspects of

  4. Development of the Neuron Assessment for Measuring Biology Students' Use of Experimental Design Concepts and Representations

    Science.gov (United States)

    Dasgupta, Annwesa P.; Anderson, Trevor R.; Pelaez, Nancy J.

    2016-01-01

    Researchers, instructors, and funding bodies in biology education are unanimous about the importance of developing students' competence in experimental design. Despite this, only limited measures are available for assessing such competence development, especially in the areas of molecular and cellular biology. Also, existing assessments do not…

  5. Digital learning material for experimental design and model building in molecular biology

    NARCIS (Netherlands)

    Aegerter-Wilmsen, T.

    2005-01-01

    Designing experimental approaches is a major cognitive skill in molecular biology research, and building models, including quantitative ones, is a cognitive skill which is rapidly gaining importance. Since molecular biology education at university level is aimed at educating future researchers, we

  6. Design and Biological Evaluation of Antifouling Dihydrostilbene Oxime Hybrids.

    Science.gov (United States)

    Moodie, Lindon W K; Cervin, Gunnar; Trepos, Rozenn; Labriere, Christophe; Hellio, Claire; Pavia, Henrik; Svenson, Johan

    2018-04-01

    By combining the recently reported repelling natural dihydrostilbene scaffold with an oxime moiety found in many marine antifoulants, a library of nine antifouling hybrid compounds was developed and biologically evaluated. The prepared compounds were shown to display a low antifouling effect against marine bacteria but a high potency against the attachment and growth of microalgae down to MIC values of 0.01 μg/mL for the most potent hybrid. The mode of action can be characterized as repelling via a reversible non-toxic biostatic mechanism. Barnacle cyprid larval settlement was also inhibited at low μg/mL concentrations with low levels or no toxicity observed. Several of the prepared compounds performed better than many reported antifouling marine natural products. While several of the prepared compounds are highly active as antifoulants, no apparent synergy is observed by incorporating the oxime functionality into the dihydrostilbene scaffold. This observation is discussed in light of recently reported literature data on related marine natural antifoulants and antifouling hybrids as a potentially general strategy for generation of improved antifoulants.

  7. Design Approach of Biologically-Inspired Musculoskeletal Humanoids

    Directory of Open Access Journals (Sweden)

    Yuto Nakanishi

    2013-04-01

    Full Text Available In order to realize more natural and various motions like humans, humanlike musculoskeletal tendon-driven humanoids have been studied. Especially, it is very challenging to design musculoskeletal body structure which consists of complicated bones, redundant powerful and flexible muscles, and large number of distributed sensors. In addition, it is very challenging to reveal humanlike intelligence to manage these complicated musculoskeletal body structure. This paper sums up life-sized musculoskeletal humanoids Kenta, Kotaro, Kenzoh and Kenshiro which we have developed so far, and describes key technologies to develop and control these robots.

  8. THE FUNCTIONS OF CATALAN EDUCATIONAL INSPECTION FROM THE CATALAN EDUCATIONAL LAW (LEC AND THE CENTERS AUTONOMY PROCESS

    Directory of Open Access Journals (Sweden)

    Joan Segura Torres

    2017-06-01

    Full Text Available Catalonia is one of the most developed community in relation to the centers autonomy. A step forward was made with of the LEC (2009 and the Centers Autonomy Decree. The role of the Educational Inspection has not been explained or revised to adapt to those new changes and how to contribute from its position. This article presents a review of all the current legislative documentation in Autonomy of Centers and Educational Inspection in Catalonia with the aim of contributing some conclusions which show us how the inspection function is positioned in developing its functions facing this situation change and suggestions about where it should lead to contribute to the improvement of educational quality. It has been carried out within the framework of the PhD Program of the Autonomous University of Barcelona.

  9. Designer genes. Recombinant antibody fragments for biological imaging

    Energy Technology Data Exchange (ETDEWEB)

    Wu, A.M.; Yazaki, P.J. [Beckman Research Institute of the City of Hope, Duarte, CA (United States). Dept. of Molecular Biology

    2000-09-01

    and expression, combined with novel specificities that will arise form advances in genomic and combinatorial approaches to target discovery, will usher in a new era of recombinant antibodies for biological imaging.

  10. Designer genes. Recombinant antibody fragments for biological imaging

    International Nuclear Information System (INIS)

    Wu, A.M.; Yazaki, P.J.

    2000-01-01

    expression, combined with novel specificities that will arise form advances in genomic and combinatorial approaches to target discovery, will usher in a new era of recombinant antibodies for biological imaging

  11. Genome-scale metabolic models as platforms for strain design and biological discovery.

    Science.gov (United States)

    Mienda, Bashir Sajo

    2017-07-01

    Genome-scale metabolic models (GEMs) have been developed and used in guiding systems' metabolic engineering strategies for strain design and development. This strategy has been used in fermentative production of bio-based industrial chemicals and fuels from alternative carbon sources. However, computer-aided hypotheses building using established algorithms and software platforms for biological discovery can be integrated into the pipeline for strain design strategy to create superior strains of microorganisms for targeted biosynthetic goals. Here, I described an integrated workflow strategy using GEMs for strain design and biological discovery. Specific case studies of strain design and biological discovery using Escherichia coli genome-scale model are presented and discussed. The integrated workflow presented herein, when applied carefully would help guide future design strategies for high-performance microbial strains that have existing and forthcoming genome-scale metabolic models.

  12. Design, synthesis and biological evaluation of novel desmuramyldipeptide analogs.

    Science.gov (United States)

    Jakopin, Žiga; Corsini, Emanuela; Gobec, Martina; Mlinarič-Raščan, Irena; Dolenc, Marija Sollner

    2011-09-01

    A series of novel desmuramyldipeptides have been designed and synthesized as part of our search for therapeutically useful muramyldipeptide (MDP) analogs. Their immunomodulatory properties were initially assessed in vitro, evaluating their effect on lipopolysaccharide (LPS)-induced cytokine release in THP-1 cells. Following the initial screening, selected compounds were further investigated for immunomodulatory properties using LPS and phorbol 12-myristate 13-acetate (PMA)/ionomycin-stimulated human peripheral blood mononuclear cells. The results confirmed the immunomodulatory properties of some of the synthesized desmuramyldipeptide analogs. Taken together, presented data confirmed the immunostimulatory effect of compound 44, MDP derivative incorporating a pyrido-fused [1,2]-benzisothiazole moiety, while for compounds 32 and 39, indole scaffold-based derivatives of MDP, an immunosuppressive effect was observed. Further studies will be necessary to address their potential therapeutic use as immunomodulatory drugs, both as immunostimulants or anti-inflammatory agents. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  13. Computational protein design-the next generation tool to expand synthetic biology applications.

    Science.gov (United States)

    Gainza-Cirauqui, Pablo; Correia, Bruno Emanuel

    2018-05-02

    One powerful approach to engineer synthetic biology pathways is the assembly of proteins sourced from one or more natural organisms. However, synthetic pathways often require custom functions or biophysical properties not displayed by natural proteins, limitations that could be overcome through modern protein engineering techniques. Structure-based computational protein design is a powerful tool to engineer new functional capabilities in proteins, and it is beginning to have a profound impact in synthetic biology. Here, we review efforts to increase the capabilities of synthetic biology using computational protein design. We focus primarily on computationally designed proteins not only validated in vitro, but also shown to modulate different activities in living cells. Efforts made to validate computational designs in cells can illustrate both the challenges and opportunities in the intersection of protein design and synthetic biology. We also highlight protein design approaches, which although not validated as conveyors of new cellular function in situ, may have rapid and innovative applications in synthetic biology. We foresee that in the near-future, computational protein design will vastly expand the functional capabilities of synthetic cells. Copyright © 2018. Published by Elsevier Ltd.

  14. Sharing Structure and Function in Biological Design with SBOL 2.0.

    Science.gov (United States)

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

    2016-06-17

    The Synthetic Biology Open Language (SBOL) is a standard that enables collaborative engineering of biological systems across different institutions and tools. SBOL is developed through careful consideration of recent synthetic biology trends, real use cases, and consensus among leading researchers in the field and members of commercial biotechnology enterprises. We demonstrate and discuss how a set of SBOL-enabled software tools can form an integrated, cross-organizational workflow to recapitulate the design of one of the largest published genetic circuits to date, a 4-input AND sensor. This design encompasses the structural components of the system, such as its DNA, RNA, small molecules, and proteins, as well as the interactions between these components that determine the system's behavior/function. The demonstrated workflow and resulting circuit design illustrate the utility of SBOL 2.0 in automating the exchange of structural and functional specifications for genetic parts, devices, and the biological systems in which they operate.

  15. Design and validation of general biology learning program based on scientific inquiry skills

    Science.gov (United States)

    Cahyani, R.; Mardiana, D.; Noviantoro, N.

    2018-03-01

    Scientific inquiry is highly recommended to teach science. The reality in the schools and colleges is that many educators still have not implemented inquiry learning because of their lack of understanding. The study aims to1) analyze students’ difficulties in learning General Biology, 2) design General Biology learning program based on multimedia-assisted scientific inquiry learning, and 3) validate the proposed design. The method used was Research and Development. The subjects of the study were 27 pre-service students of general elementary school/Islamic elementary schools. The workflow of program design includes identifying learning difficulties of General Biology, designing course programs, and designing instruments and assessment rubrics. The program design is made for four lecture sessions. Validation of all learning tools were performed by expert judge. The results showed that: 1) there are some problems identified in General Biology lectures; 2) the designed products include learning programs, multimedia characteristics, worksheet characteristics, and, scientific attitudes; and 3) expert validation shows that all program designs are valid and can be used with minor revisions. The first section in your paper.

  16. 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.

  17. Biomimicry, Biofabrication, and Biohybrid Systems: The Emergence and Evolution of Biological Design.

    Science.gov (United States)

    Raman, Ritu; Bashir, Rashid

    2017-10-01

    The discipline of biological design has a relatively short history, but has undergone very rapid expansion and development over that time. This Progress Report outlines the evolution of this field from biomimicry to biofabrication to biohybrid systems' design, showcasing how each subfield incorporates bioinspired dynamic adaptation into engineered systems. Ethical implications of biological design are discussed, with an emphasis on establishing responsible practices for engineering non-natural or hypernatural functional behaviors in biohybrid systems. This report concludes with recommendations for implementing biological design into educational curricula, ensuring effective and responsible practices for the next generation of engineers and scientists. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Holarchical Systems and Emotional Holons : Biologically-Inspired System Designs for Control of Autonomous Aerial Vehicles

    Science.gov (United States)

    Ippolito, Corey; Plice, Laura; Pisanich, Greg

    2003-01-01

    The BEES (Bio-inspired Engineering for Exploration Systems) for Mars project at NASA Ames Research Center has the goal of developing bio-inspired flight control strategies to enable aerial explorers for Mars scientific investigations. This paper presents a summary of our ongoing research into biologically inspired system designs for control of unmanned autonomous aerial vehicle communities for Mars exploration. First, we present cooperative design considerations for robotic explorers based on the holarchical nature of biological systems and communities. Second, an outline of an architecture for cognitive decision making and control of individual robotic explorers is presented, modeled after the emotional nervous system of cognitive biological systems. Keywords: Holarchy, Biologically Inspired, Emotional UAV Flight Control

  19. Ectopic overexpression of castor bean LEAFY COTYLEDON2 (LEC2 in Arabidopsis triggers the expression of genes that encode regulators of seed maturation and oil body proteins in vegetative tissues

    Directory of Open Access Journals (Sweden)

    Hyun Uk Kim

    2014-01-01

    Full Text Available The LEAFY COTYLEDON2 (LEC2 gene plays critically important regulatory roles during both early and late embryonic development. Here, we report the identification of the LEC2 gene from the castor bean plant (Ricinus communis, and characterize the effects of its overexpression on gene regulation and lipid metabolism in transgenic Arabidopsis plants. LEC2 exists as a single-copy gene in castor bean, is expressed predominantly in embryos, and encodes a protein with a conserved B3 domain, but different N- and C-terminal domains to those found in LEC2 from Arabidopsis. Ectopic overexpression of LEC2 from castor bean under the control of the cauliflower mosaic virus (CaMV 35S promoter in Arabidopsis plants induces the accumulation of transcripts that encodes five major transcription factors (the LEAFY COTYLEDON1 (LEC1, LEAFY COTYLEDON1-LIKE (L1L, FUSCA3 (FUS3, and ABSCISIC ACID INSENSITIVE 3 (ABI3 transcripts for seed maturation, and WRINKELED1 (WRI1 transcripts for fatty acid biosynthesis, as well as OLEOSIN transcripts for the formation of oil bodies in vegetative tissues. Transgenic Arabidopsis plants that express the LEC2 gene from castor bean show a range of dose-dependent morphological phenotypes and effects on the expression of LEC2-regulated genes during seedling establishment and vegetative growth. Expression of castor bean LEC2 in Arabidopsis increased the expression of fatty acid elongase 1 (FAE1 and induced the accumulation of triacylglycerols, especially those containing the seed-specific fatty acid, eicosenoic acid (20:1Δ11, in vegetative tissues.

  20. Ectopic overexpression of castor bean LEAFY COTYLEDON2 (LEC2) in Arabidopsis triggers the expression of genes that encode regulators of seed maturation and oil body proteins in vegetative tissues.

    Science.gov (United States)

    Kim, Hyun Uk; Jung, Su-Jin; Lee, Kyeong-Ryeol; Kim, Eun Ha; Lee, Sang-Min; Roh, Kyung Hee; Kim, Jong-Bum

    2013-01-01

    The LEAFY COTYLEDON2 (LEC2) gene plays critically important regulatory roles during both early and late embryonic development. Here, we report the identification of the LEC2 gene from the castor bean plant (Ricinus communis), and characterize the effects of its overexpression on gene regulation and lipid metabolism in transgenic Arabidopsis plants. LEC2 exists as a single-copy gene in castor bean, is expressed predominantly in embryos, and encodes a protein with a conserved B3 domain, but different N- and C-terminal domains to those found in LEC2 from Arabidopsis. Ectopic overexpression of LEC2 from castor bean under the control of the cauliflower mosaic virus (CaMV) 35S promoter in Arabidopsis plants induces the accumulation of transcripts that encodes five major transcription factors (the LEAFY COTYLEDON1 (LEC1), LEAFY COTYLEDON1-LIKE (L1L), FUSCA3 (FUS3), and ABSCISIC ACID INSENSITIVE 3 (ABI3) transcripts for seed maturation, and WRINKELED1 (WRI1) transcripts for fatty acid biosynthesis), as well as OLEOSIN transcripts for the formation of oil bodies in vegetative tissues. Transgenic Arabidopsis plants that express the LEC2 gene from castor bean show a range of dose-dependent morphological phenotypes and effects on the expression of LEC2-regulated genes during seedling establishment and vegetative growth. Expression of castor bean LEC2 in Arabidopsis increased the expression of fatty acid elongase 1 (FAE1) and induced the accumulation of triacylglycerols, especially those containing the seed-specific fatty acid, eicosenoic acid (20:1(Δ11)), in vegetative tissues.

  1. Ectopic overexpression of castor bean LEAFY COTYLEDON2 (LEC2) in Arabidopsis triggers the expression of genes that encode regulators of seed maturation and oil body proteins in vegetative tissues☆

    Science.gov (United States)

    Kim, Hyun Uk; Jung, Su-Jin; Lee, Kyeong-Ryeol; Kim, Eun Ha; Lee, Sang-Min; Roh, Kyung Hee; Kim, Jong-Bum

    2013-01-01

    The LEAFY COTYLEDON2 (LEC2) gene plays critically important regulatory roles during both early and late embryonic development. Here, we report the identification of the LEC2 gene from the castor bean plant (Ricinus communis), and characterize the effects of its overexpression on gene regulation and lipid metabolism in transgenic Arabidopsis plants. LEC2 exists as a single-copy gene in castor bean, is expressed predominantly in embryos, and encodes a protein with a conserved B3 domain, but different N- and C-terminal domains to those found in LEC2 from Arabidopsis. Ectopic overexpression of LEC2 from castor bean under the control of the cauliflower mosaic virus (CaMV) 35S promoter in Arabidopsis plants induces the accumulation of transcripts that encodes five major transcription factors (the LEAFY COTYLEDON1 (LEC1), LEAFY COTYLEDON1-LIKE (L1L), FUSCA3 (FUS3), and ABSCISIC ACID INSENSITIVE 3 (ABI3) transcripts for seed maturation, and WRINKELED1 (WRI1) transcripts for fatty acid biosynthesis), as well as OLEOSIN transcripts for the formation of oil bodies in vegetative tissues. Transgenic Arabidopsis plants that express the LEC2 gene from castor bean show a range of dose-dependent morphological phenotypes and effects on the expression of LEC2-regulated genes during seedling establishment and vegetative growth. Expression of castor bean LEC2 in Arabidopsis increased the expression of fatty acid elongase 1 (FAE1) and induced the accumulation of triacylglycerols, especially those containing the seed-specific fatty acid, eicosenoic acid (20:1Δ11), in vegetative tissues. PMID:24363987

  2. Comparing novelty of designs from biological-inspiration with those from brainstorming

    DEFF Research Database (Denmark)

    Keshwani, Sonal; Lenau, Torben Anker; Ahmed-Kristensen, Saeema

    2017-01-01

    This research aims to understand the significance of biological-analogies in fostering novelty by comparing biological-analogies with other design methods for idea generation. Among other design methods, brainstorming was chosen here as benchmark. Four studies were conducted to compare: (i......) the levels of abstraction at which concepts were ideated using biological inspiration (represented using biocards) with that using traditional brainstorming; and (ii) the novelty of concepts produced by using these two design methods. Concepts produced in these studies were evaluated for levels...... of abstraction at which they were ideated, average novelty, and proportion of high-novelty concepts. Results suggest that concepts generated using biocards were ideated at higher abstraction levels than those using brainstorming, but neither were at the highest abstraction levels. The average novelty of concepts...

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

    Science.gov (United States)

    Lewens, Tim

    2013-12-01

    Synthetic biology is often described as a project that applies rational design methods to the organic world. Although humans have influenced organic lineages in many ways, it is nonetheless reasonable to place synthetic biology towards one end of a continuum between purely 'blind' processes of organic modification at one extreme, and wholly rational, design-led processes at the other. An example from evolutionary electronics illustrates some of the constraints imposed by the rational design methodology itself. These constraints reinforce the limitations of the synthetic biology ideal, limitations that are often freely acknowledged by synthetic biology's own practitioners. The synthetic biology methodology reflects a series of constraints imposed on finite human designers who wish, as far as is practicable, to communicate with each other and to intervene in nature in reasonably targeted and well-understood ways. This is better understood as indicative of an underlying awareness of human limitations, rather than as expressive of an objectionable impulse to mastery over nature. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Traditional Versus Online Biology Courses: Connecting Course Design and Student Learning in an Online Setting.

    Science.gov (United States)

    Biel, Rachel; Brame, Cynthia J

    2016-12-01

    Online courses are a large and growing part of the undergraduate education landscape, but many biology instructors are skeptical about the effectiveness of online instruction. We reviewed studies comparing the effectiveness of online and face-to-face (F2F) undergraduate biology courses. Five studies compared student performance in multiple course sections at community colleges, while eight were smaller scale and compared student performance in particular biology courses at a variety of types of institutions. Of the larger-scale studies, two found that students in F2F sections outperformed students in online sections, and three found no significant difference; it should be noted, however, that these studies reported little information about course design. Of the eight smaller scale studies, six found no significant difference in student performance between the F2F and online sections, while two found that the online sections outperformed the F2F sections. In alignment with general findings about online teaching and learning, these results suggest that well-designed online biology courses can be effective at promoting student learning. Three recommendations for effective online instruction in biology are given: the inclusion of an online orientation to acclimate students to the online classroom; student-instructor and student-student interactions facilitated through synchronous and asynchronous communication; and elements that prompt student reflection and self-assessment. We conclude that well-designed online biology courses can be as effective as their traditional counterparts, but that more research is needed to elucidate specific course elements and structures that can maximize online students' learning of key biology skills and concepts.

  5. Traditional Versus Online Biology Courses: Connecting Course Design and Student Learning in an Online Setting

    Directory of Open Access Journals (Sweden)

    Rachel Biel

    2016-12-01

    Full Text Available Online courses are a large and growing part of the undergraduate education landscape, but many biology instructors are skeptical about the effectiveness of online instruction. We reviewed studies comparing the effectiveness of online and face-to-face (F2F undergraduate biology courses. Five studies compared student performance in multiple course sections at community colleges, while eight were smaller scale and compared student performance in particular biology courses at a variety of types of institutions. Of the larger-scale studies, two found that students in F2F sections outperformed students in online sections, and three found no significant difference; it should be noted, however, that these studies reported little information about course design. Of the eight smaller scale studies, six found no significant difference in student performance between the F2F and online sections, while two found that the online sections outperformed the F2F sections. In alignment with general findings about online teaching and learning, these results suggest that well-designed online biology courses can be effective at promoting student learning. Three recommendations for effective online instruction in biology are given: the inclusion of an online orientation to acclimate students to the online classroom; student-instructor and student-student interactions facilitated through synchronous and asynchronous communication; and elements that prompt student reflection and self-assessment. We conclude that well-designed online biology courses can be as effective as their traditional counterparts, but that more research is needed to elucidate specific course elements and structures that can maximize online students’ learning of key biology skills and concepts.

  6. Development of biological criteria for the design of advanced hydropower turbines

    Energy Technology Data Exchange (ETDEWEB)

    Cada, Glenn F. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Coutant, Charles C. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Whitney, Richard R. [Leavenworth, WA (United States)

    1997-03-01

    A review of the literature related to turbine-passage injury mechanisms suggests the following biological criteria should be considered in the design of new turbines: (1) pressure; (2) cavitation; (3) shear and turbulence; and (4) mechanical injury. Based on the study’s review of fish behavior in relation to hydropower facilities, it provides a number of recommendations to guide both turbine design and additional research.

  7. Designing and evaluating a context-based lesson sequence promoting conceptual coherence in biology

    NARCIS (Netherlands)

    Ummels, M. H J; Kamp, M. J A; De Kroon, H.; Boersma, K. Th|info:eu-repo/dai/nl/073043141

    2015-01-01

    Context-based education, in which students deal with biological concepts in a meaningful way, is showing promise in promoting the development of students conceptual coherence. However, literature gives little guidance about how this kind of education should be designed. Therefore, our study aims at

  8. A positron annihilation study of compensation defects responsible for conduction-type conversions in LEC-grown InP

    International Nuclear Information System (INIS)

    Shan, Y.Y.; Ling, C.C.; Fung, S.; Beling, C.D.; Zhao, Y.W.

    2001-01-01

    Positron annihilation techniques have been employed to investigate the formation of vacancy type of compensation defects in undoped LEC-grown InP. N-type InP becomes p-type semiconducting by short time annealing at 700 C, and then turns to be n-type again after further annealing but with a much higher resistivity. Positron lifetime measurements show that the positron average lifetime τ av increases to a high value of 247ps for the first n-type to p-type conversion and decreases to 240ps for the following p-type to n-type conversion. τ av increases slightly and saturates at 242ps upon further annealing. The results of positron annihilation Doppler-broadening measurements are consistent with the positron lifetime measurements. The correlation between the characteristics of positron annihilation and the conversions of conduction type indicates that the formation of vacancy type defects and the progressive variation of their concentrations during annealing are critical to the electrical properties of the bulk InP material. (orig.)

  9. 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

  10. Mixed-Methods Design in Biology Education Research: Approach and Uses

    Science.gov (United States)

    Warfa, Abdi-Rizak M.

    2016-01-01

    Educational research often requires mixing different research methodologies to strengthen findings, better contextualize or explain results, or minimize the weaknesses of a single method. This article provides practical guidelines on how to conduct such research in biology education, with a focus on mixed-methods research (MMR) that uses both quantitative and qualitative inquiries. Specifically, the paper provides an overview of mixed-methods design typologies most relevant in biology education research. It also discusses common methodological issues that may arise in mixed-methods studies and ways to address them. The paper concludes with recommendations on how to report and write about MMR. PMID:27856556

  11. Designing a 'neotissue' using the principles of biology, chemistry and engineering.

    Science.gov (United States)

    Nannaparaju, Madhusudhan; Oragui, Emeka; Khan, Wasim S

    2012-01-01

    The traditional methods of treating musculoskeletal injuries and disorders are not completely effective and have several limitations. Tissue engineering involves using the principles of biology, chemistry and engineering to design a 'neotissue' that augments a malfunctioning in vivo tissue. The main requirements for functional engineered tissue include reparative cellular components that proliferate on a scaffold grown within a bioreactor that provides specific biochemical and physical signals to regulate cell differentiation and tissue assembly. In this review we provide an overview of the biology of common musculoskeletal tissue and discuss their common pathologies. We also describe the commonly used stem cells, scaffolds and bioreactors and evaluate their role in issue engineering.

  12. A design concept of parallel elasticity extracted from biological muscles for engineered actuators.

    Science.gov (United States)

    Chen, Jie; Jin, Hongzhe; Iida, Fumiya; Zhao, Jie

    2016-08-23

    Series elastic actuation that takes inspiration from biological muscle-tendon units has been extensively studied and used to address the challenges (e.g. energy efficiency, robustness) existing in purely stiff robots. However, there also exists another form of passive property in biological actuation, parallel elasticity within muscles themselves, and our knowledge of it is limited: for example, there is still no general design strategy for the elasticity profile. When we look at nature, on the other hand, there seems a universal agreement in biological systems: experimental evidence has suggested that a concave-upward elasticity behaviour is exhibited within the muscles of animals. Seeking to draw possible design clues for elasticity in parallel with actuators, we use a simplified joint model to investigate the mechanisms behind this biologically universal preference of muscles. Actuation of the model is identified from general biological joints and further reduced with a specific focus on muscle elasticity aspects, for the sake of easy implementation. By examining various elasticity scenarios, one without elasticity and three with elasticity of different profiles, we find that parallel elasticity generally exerts contradictory influences on energy efficiency and disturbance rejection, due to the mechanical impedance shift thus caused. The trade-off analysis between them also reveals that concave parallel elasticity is able to achieve a more advantageous balance than linear and convex ones. It is expected that the results could contribute to our further understanding of muscle elasticity and provide a theoretical guideline on how to properly design parallel elasticity behaviours for engineering systems such as artificial actuators and robotic joints.

  13. On Designing Multicore-Aware Simulators for Systems Biology Endowed with OnLine Statistics

    Directory of Open Access Journals (Sweden)

    Marco Aldinucci

    2014-01-01

    Full Text Available The paper arguments are on enabling methodologies for the design of a fully parallel, online, interactive tool aiming to support the bioinformatics scientists .In particular, the features of these methodologies, supported by the FastFlow parallel programming framework, are shown on a simulation tool to perform the modeling, the tuning, and the sensitivity analysis of stochastic biological models. A stochastic simulation needs thousands of independent simulation trajectories turning into big data that should be analysed by statistic and data mining tools. In the considered approach the two stages are pipelined in such a way that the simulation stage streams out the partial results of all simulation trajectories to the analysis stage that immediately produces a partial result. The simulation-analysis workflow is validated for performance and effectiveness of the online analysis in capturing biological systems behavior on a multicore platform and representative proof-of-concept biological systems. The exploited methodologies include pattern-based parallel programming and data streaming that provide key features to the software designers such as performance portability and efficient in-memory (big data management and movement. Two paradigmatic classes of biological systems exhibiting multistable and oscillatory behavior are used as a testbed.

  14. On designing multicore-aware simulators for systems biology endowed with OnLine statistics.

    Science.gov (United States)

    Aldinucci, Marco; Calcagno, Cristina; Coppo, Mario; Damiani, Ferruccio; Drocco, Maurizio; Sciacca, Eva; Spinella, Salvatore; Torquati, Massimo; Troina, Angelo

    2014-01-01

    The paper arguments are on enabling methodologies for the design of a fully parallel, online, interactive tool aiming to support the bioinformatics scientists .In particular, the features of these methodologies, supported by the FastFlow parallel programming framework, are shown on a simulation tool to perform the modeling, the tuning, and the sensitivity analysis of stochastic biological models. A stochastic simulation needs thousands of independent simulation trajectories turning into big data that should be analysed by statistic and data mining tools. In the considered approach the two stages are pipelined in such a way that the simulation stage streams out the partial results of all simulation trajectories to the analysis stage that immediately produces a partial result. The simulation-analysis workflow is validated for performance and effectiveness of the online analysis in capturing biological systems behavior on a multicore platform and representative proof-of-concept biological systems. The exploited methodologies include pattern-based parallel programming and data streaming that provide key features to the software designers such as performance portability and efficient in-memory (big) data management and movement. Two paradigmatic classes of biological systems exhibiting multistable and oscillatory behavior are used as a testbed.

  15. Modular design of synthetic gene circuits with biological parts and pools.

    Science.gov (United States)

    Marchisio, Mario Andrea

    2015-01-01

    Synthetic gene circuits can be designed in an electronic fashion by displaying their basic components-Standard Biological Parts and Pools of molecules-on the computer screen and connecting them with hypothetical wires. This procedure, achieved by our add-on for the software ProMoT, was successfully applied to bacterial circuits. Recently, we have extended this design-methodology to eukaryotic cells. Here, highly complex components such as promoters and Pools of mRNA contain hundreds of species and reactions whose calculation demands a rule-based modeling approach. We showed how to build such complex modules via the joint employment of the software BioNetGen (rule-based modeling) and ProMoT (modularization). In this chapter, we illustrate how to utilize our computational tool for synthetic biology with the in silico implementation of a simple eukaryotic gene circuit that performs the logic AND operation.

  16. PASS-predicted design, synthesis and biological evaluation of cyclic nitrones as nootropics.

    Science.gov (United States)

    Marwaha, Alka; Goel, R K; Mahajan, Mohinder P

    2007-09-15

    Out of 400 virtually designed imidazoline N-oxides, five cyclic nitrones were selected on the basis of PASS prediction as potent nootropics and were evaluated for their biological activities in albino mice. The selected N-alkyl and aryl-substituted nitrones were found to be excellent nootropics. A series of lead compounds acting as cognition enhancers have been provided, which can be further exploited in search of such New Chemical Entities (NCEs).

  17. Biological assessment of the advanced turbine design at Wanapum Dam, 2005

    Energy Technology Data Exchange (ETDEWEB)

    Dauble, D. D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Deng, Z. D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Richmond, M. C. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Moursund, R. A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Carlson, T. J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Rakowski, C. L. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Duncan, J. P. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2007-08-01

    Three studies were conducted to evaluate the biological performance of an advanced design turbine installed at Unit 8 of Wanapum Dam on the Columbia River in 2005 versus a conventional Kaplan turbine, Unit 9. The studies included an evaluation of blade-strike using deterministic and probabilistic models, integrated analysis of the response of the Sensor Fish to sever hydraulic events within the turbine system, and a novel dye technique to measure injury to juvenile salmonids in the field.

  18. Combined Model of Intrinsic and Extrinsic Variability for Computational Network Design with Application to Synthetic Biology

    Science.gov (United States)

    Toni, Tina; Tidor, Bruce

    2013-01-01

    Biological systems are inherently variable, with their dynamics influenced by intrinsic and extrinsic sources. These systems are often only partially characterized, with large uncertainties about specific sources of extrinsic variability and biochemical properties. Moreover, it is not yet well understood how different sources of variability combine and affect biological systems in concert. To successfully design biomedical therapies or synthetic circuits with robust performance, it is crucial to account for uncertainty and effects of variability. Here we introduce an efficient modeling and simulation framework to study systems that are simultaneously subject to multiple sources of variability, and apply it to make design decisions on small genetic networks that play a role of basic design elements of synthetic circuits. Specifically, the framework was used to explore the effect of transcriptional and post-transcriptional autoregulation on fluctuations in protein expression in simple genetic networks. We found that autoregulation could either suppress or increase the output variability, depending on specific noise sources and network parameters. We showed that transcriptional autoregulation was more successful than post-transcriptional in suppressing variability across a wide range of intrinsic and extrinsic magnitudes and sources. We derived the following design principles to guide the design of circuits that best suppress variability: (i) high protein cooperativity and low miRNA cooperativity, (ii) imperfect complementarity between miRNA and mRNA was preferred to perfect complementarity, and (iii) correlated expression of mRNA and miRNA – for example, on the same transcript – was best for suppression of protein variability. Results further showed that correlations in kinetic parameters between cells affected the ability to suppress variability, and that variability in transient states did not necessarily follow the same principles as variability in the steady

  19. Supporting cognition in systems biology analysis: findings on users' processes and design implications.

    Science.gov (United States)

    Mirel, Barbara

    2009-02-13

    Current usability studies of bioinformatics tools suggest that tools for exploratory analysis support some tasks related to finding relationships of interest but not the deep causal insights necessary for formulating plausible and credible hypotheses. To better understand design requirements for gaining these causal insights in systems biology analyses a longitudinal field study of 15 biomedical researchers was conducted. Researchers interacted with the same protein-protein interaction tools to discover possible disease mechanisms for further experimentation. Findings reveal patterns in scientists' exploratory and explanatory analysis and reveal that tools positively supported a number of well-structured query and analysis tasks. But for several of scientists' more complex, higher order ways of knowing and reasoning the tools did not offer adequate support. Results show that for a better fit with scientists' cognition for exploratory analysis systems biology tools need to better match scientists' processes for validating, for making a transition from classification to model-based reasoning, and for engaging in causal mental modelling. As the next great frontier in bioinformatics usability, tool designs for exploratory systems biology analysis need to move beyond the successes already achieved in supporting formulaic query and analysis tasks and now reduce current mismatches with several of scientists' higher order analytical practices. The implications of results for tool designs are discussed.

  20. Building Design Guidelines of Interior Architecture for Bio safety Levels of Biology Laboratories

    International Nuclear Information System (INIS)

    ElDib, A.A.

    2014-01-01

    This paper discusses the pivotal role of the Interior Architecture As one of the scientific disciplines minute to complete the Architectural Sciences, which relied upon the achievement and development of facilities containing scientific research laboratories, in terms of planning and design, particularly those containing biological laboratories using radioactive materials, adding to that, the application of the materials or raw materials commensurate with each discipline of laboratory and its work nature, and by the discussion the processing of design techniques and requirements of interior architecture dealing with Research Laboratory for electronic circuits an their applications with the making of its prototypes

  1. Ultra-Structure database design methodology for managing systems biology data and analyses

    Directory of Open Access Journals (Sweden)

    Hemminger Bradley M

    2009-08-01

    Full Text Available Abstract Background Modern, high-throughput biological experiments generate copious, heterogeneous, interconnected data sets. Research is dynamic, with frequently changing protocols, techniques, instruments, and file formats. Because of these factors, systems designed to manage and integrate modern biological data sets often end up as large, unwieldy databases that become difficult to maintain or evolve. The novel rule-based approach of the Ultra-Structure design methodology presents a potential solution to this problem. By representing both data and processes as formal rules within a database, an Ultra-Structure system constitutes a flexible framework that enables users to explicitly store domain knowledge in both a machine- and human-readable form. End users themselves can change the system's capabilities without programmer intervention, simply by altering database contents; no computer code or schemas need be modified. This provides flexibility in adapting to change, and allows integration of disparate, heterogenous data sets within a small core set of database tables, facilitating joint analysis and visualization without becoming unwieldy. Here, we examine the application of Ultra-Structure to our ongoing research program for the integration of large proteomic and genomic data sets (proteogenomic mapping. Results We transitioned our proteogenomic mapping information system from a traditional entity-relationship design to one based on Ultra-Structure. Our system integrates tandem mass spectrum data, genomic annotation sets, and spectrum/peptide mappings, all within a small, general framework implemented within a standard relational database system. General software procedures driven by user-modifiable rules can perform tasks such as logical deduction and location-based computations. The system is not tied specifically to proteogenomic research, but is rather designed to accommodate virtually any kind of biological research. Conclusion We find

  2. The biological shield of a high-intensity spallation source: a monte Carlo design study

    International Nuclear Information System (INIS)

    Koprivnikar, I.; Schachinger, E.

    2004-01-01

    The design of high-intensity spallation sources requires the best possible estimates for the biological shield. The applicability of three-dimensional Monte Carlo simulation in the design of the biological shield of a spallation source will be discussed. In order to achieve reasonable computing times along with acceptable accuracy, biasing techniques are to be employed and it was the main purpose of this work to develop a strategy for an effective Monte Carlo simulation in shielding design. The most prominent MC computer codes, namely MCNPX and FLUKA99, have been applied to the same model spallation source (the European Spallation Source) and on the basis of the derived strategies, the design and characteristics of the target station shield are discussed. It is also the purpose of the paper to demonstrate the application of the developed strategy for the design of beam lines with their shielding using as an example the target-moderator-reflector complex of the ESS as the primary particle source. (author)

  3. 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.

  4. Strategies for Assessment of the Biological Performance and Design of Hydroturbines

    Energy Technology Data Exchange (ETDEWEB)

    Carlson, Thomas J.; Richmond, Marshall C.

    2011-05-05

    The biological response of fish to turbine passage has been of concern for several decades and emphasized recently by consideration of hydro as a 'green' power source. The current state-of-the-art of hydro-turbine biological performance assessment, while still inadequate, has advanced considerably the past 10 years. For example, the importance of assessment of exposure to pressure changes during turbine passage has been emphasized by findings of laboratory studies of rapid decompression. It is now very clear that hydroturbine biological assessment must consider the physiological state and behavior of fish at turbine entry and changes in physiological state that drive aspects of behavior during tailrace passage. Such considerations are in addition to concerns about exposure of fish to mechanical and pressure sources of injury during turbine passage. Experimental designs and assessment tools have evolved for acclimation of test fish, observation of test fish behavior at approach and upon exit from the turbine environment, and precise estimation of turbine passage mortality. Fish condition assessment continues to improve permitting better classification of observed injuries to injury mechanisms. Computational fluid dynamics (CFD) models and other computer models permit detailed investigation of the turbine passage environment and development of hypotheses that can be tested in field studies using live fish. Risk assessment techniques permit synthesis of laboratory and in-field study findings and estimation of population level effects over a wide range of turbine operation scenarios. Risk assessment is also evolving to provide input to turbine runner design. These developments, and others, have resulted in more productive biological performance assessment studies and will continue to evolve and improve the quantity and quality of information obtained from costly live fish hydroturbine passage studies. This paper reviews the history of hydro-turbine biological

  5. 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

  6. Mixed-Methods Design in Biology Education Research: Approach and Uses.

    Science.gov (United States)

    Warfa, Abdi-Rizak M

    Educational research often requires mixing different research methodologies to strengthen findings, better contextualize or explain results, or minimize the weaknesses of a single method. This article provides practical guidelines on how to conduct such research in biology education, with a focus on mixed-methods research (MMR) that uses both quantitative and qualitative inquiries. Specifically, the paper provides an overview of mixed-methods design typologies most relevant in biology education research. It also discusses common methodological issues that may arise in mixed-methods studies and ways to address them. The paper concludes with recommendations on how to report and write about MMR. © 2016 L. A.-R. M. Warfa. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  7. Biological shielding design and qualification of concreting process for construction of electron beam irradiation facility

    International Nuclear Information System (INIS)

    Petwal, V.C.; Kumar, P.; Suresh, N.; Parchani, G.; Dwivedi, J.; Thakurta, A.C.

    2011-01-01

    A technology demonstration facility for irradiation of food and agricultural products is being set-up by RRCAT at Indore. The facility design is based on linear electron accelerator with maximum beam power of 10 kW and can be operated either in electron mode at 10 MeV or photon modes at 5/7.5 MeV. Biological shielding has been designed in accordance with NCRP 51 to achieve dose rate at all accessible points outside the irradiation vault less than the permissible limit of 0.1 mR/hr. In addition to radiation attenuation property, concrete must have satisfactory mechanical properties to meet the structural requirements. There are number of site specific variables which affect the structural, thermal and radiological properties of concrete, leading to considerable difference in actual values and design values. Hence it is essential to establish a suitable site and environmental specific process to cast the concrete and qualify the process by experimental measurement. For process qualification we have cast concrete test blocks of different thicknesses up to 3.25 m and evaluated the radiological and mechanical properties by radiometry, ultrasonic and mechanical tests. In this paper we describe the biological shielding design of the facility and analyse the results of tests carried out for qualification of the process. (author)

  8. Design in nature how the constructal law governs evolution in biology, physics, technology, and social organization

    CERN Document Server

    Bejan, Adrian

    2013-01-01

    In this groundbreaking book, Adrian Bejan takes the recurring patterns in nature—trees, tributaries, air passages, neural networks, and lightning bolts—and reveals how a single principle of physics, the constructal law, accounts for the evolution of these and many other designs in our world. Everything—from biological life to inanimate systems—generates shape and structure and evolves in a sequence of ever-improving designs in order to facilitate flow. River basins, cardiovascular systems, and bolts of lightning are very efficient flow systems to move a current—of water, blood, or electricity. Likewise, the more complex architecture of animals evolve to cover greater distance per unit of useful energy, or increase their flow across the land. Such designs also appear in human organizations, like the hierarchical “flowcharts” or reporting structures in corporations and political bodies. All are governed by the same principle, known as the constructal law, and configure and reconfigure themselves...

  9. Efficient high-throughput biological process characterization: Definitive screening design with the ambr250 bioreactor system.

    Science.gov (United States)

    Tai, Mitchell; Ly, Amanda; Leung, Inne; Nayar, Gautam

    2015-01-01

    The burgeoning pipeline for new biologic drugs has increased the need for high-throughput process characterization to efficiently use process development resources. Breakthroughs in highly automated and parallelized upstream process development have led to technologies such as the 250-mL automated mini bioreactor (ambr250™) system. Furthermore, developments in modern design of experiments (DoE) have promoted the use of definitive screening design (DSD) as an efficient method to combine factor screening and characterization. Here we utilize the 24-bioreactor ambr250™ system with 10-factor DSD to demonstrate a systematic experimental workflow to efficiently characterize an Escherichia coli (E. coli) fermentation process for recombinant protein production. The generated process model is further validated by laboratory-scale experiments and shows how the strategy is useful for quality by design (QbD) approaches to control strategies for late-stage characterization. © 2015 American Institute of Chemical Engineers.

  10. Developing optimal input design strategies in cancer systems biology with applications to microfluidic device engineering.

    Science.gov (United States)

    Menolascina, Filippo; Bellomo, Domenico; Maiwald, Thomas; Bevilacqua, Vitoantonio; Ciminelli, Caterina; Paradiso, Angelo; Tommasi, Stefania

    2009-10-15

    Mechanistic models are becoming more and more popular in Systems Biology; identification and control of models underlying biochemical pathways of interest in oncology is a primary goal in this field. Unfortunately the scarce availability of data still limits our understanding of the intrinsic characteristics of complex pathologies like cancer: acquiring information for a system understanding of complex reaction networks is time consuming and expensive. Stimulus response experiments (SRE) have been used to gain a deeper insight into the details of biochemical mechanisms underlying cell life and functioning. Optimisation of the input time-profile, however, still remains a major area of research due to the complexity of the problem and its relevance for the task of information retrieval in systems biology-related experiments. We have addressed the problem of quantifying the information associated to an experiment using the Fisher Information Matrix and we have proposed an optimal experimental design strategy based on evolutionary algorithm to cope with the problem of information gathering in Systems Biology. On the basis of the theoretical results obtained in the field of control systems theory, we have studied the dynamical properties of the signals to be used in cell stimulation. The results of this study have been used to develop a microfluidic device for the automation of the process of cell stimulation for system identification. We have applied the proposed approach to the Epidermal Growth Factor Receptor pathway and we observed that it minimises the amount of parametric uncertainty associated to the identified model. A statistical framework based on Monte-Carlo estimations of the uncertainty ellipsoid confirmed the superiority of optimally designed experiments over canonical inputs. The proposed approach can be easily extended to multiobjective formulations that can also take advantage of identifiability analysis. Moreover, the availability of fully automated

  11. 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.

  12. Application of radiochemical methods for development of new biological preparation designed for soil bioremediation

    International Nuclear Information System (INIS)

    Kim, A.A.; Djuraeva, G.T.; Djumaniyazova, G.I.; Yadgarov, Kh.T.

    2006-01-01

    Full text: Internationally the bioremediation of agricultural lands contaminated by persistent chloroorganic compounds by means of the microbial methods are used as the most low-cost and the most effective. One of the factors reducing efficacy of microbial degradation, is often the low quantity of microorganisms - destructors in the soil. Therefore, we have designed bioremediation technology of soils, contaminated by organochlorine compounds, with use of the alive microorganisms as active agent. We developed the biological preparation containing 5 aboriginal active strains of bacteria - destructors of persistent chloroorganic compounds and investigated the ability of biological preparation to increase the bioremediation potential of contaminated soils. To carry out the investigation we developed the complex of radiochemical methods with use of tritium labeled PCBs, including the following methods: 1.The method to define the accumulation and degradation of PCBs in soil bacteria in culture allows determination of quantitative characteristics of bacterial strains. 2. The method to define the PCBs degradation by soil bacteria strains in model conditions in the soil allows to estimate the PCB-destructive activity of strains after introducing in soil. 3. A method to define the PCB-destructive activity of own microbiota of contaminated soil. 4. A method to define the effect of stimulation of the PCB-destructive activity of biological preparation and own microbiota of soil with the help of biofertilizers. By using the developed radiochemical methods we have carried out investigation on creation of new biological preparation on the basis of strains of soil bacteria - destructors of PCBs. We also determined the quality and quantity characteristics of HCCH and PCBs-destructive activity of new biological preparation. It is shown that the new biological preparation is capable of accumulation and destruction of the PCBs in culture and in soil at model conditions. Thus, the

  13. Design of a Comprehensive Biochemistry and Molecular Biology Experiment: Phase Variation Caused by Recombinational Regulation of Bacterial Gene Expression

    Science.gov (United States)

    Sheng, Xiumei; Xu, Shungao; Lu, Renyun; Isaac, Dadzie; Zhang, Xueyi; Zhang, Haifang; Wang, Huifang; Qiao, Zheng; Huang, Xinxiang

    2014-01-01

    Scientific experiments are indispensable parts of Biochemistry and Molecular Biology. In this study, a comprehensive Biochemistry and Molecular Biology experiment about "Salmonella enterica" serovar Typhi Flagellar phase variation has been designed. It consisted of three parts, namely, inducement of bacterial Flagellar phase variation,…

  14. Designing and testing a classroom curriculum to teach preschoolers about the biology of physical activity: The respiration system as an underlying biological causal mechanism

    Science.gov (United States)

    Ewing, Tracy S.

    The present study examined young children's understanding of respiration and oxygen as a source of vital energy underlying physical activity. Specifically, the purpose of the study was to explore whether a coherent biological theory, characterized by an understanding that bodily parts (heart and lungs) and processes (oxygen in respiration) as part of a biological system, can be taught as a foundational concept to reason about physical activity. The effects of a biology-based intervention curriculum designed to teach preschool children about bodily functions as a part of the respiratory system, the role of oxygen as a vital substance and how physical activity acts an energy source were examined. Participants were recruited from three private preschool classrooms (two treatment; 1 control) in Southern California and included a total of 48 four-year-old children (30 treatment; 18 control). Findings from this study suggested that young children could be taught relevant biological concepts about the role of oxygen in respiratory processes. Children who received biology-based intervention curriculum made significant gains in their understanding of the biology of respiration, identification of physical and sedentary activities. In addition these children demonstrated that coherence of conceptual knowledge was correlated with improved accuracy at activity identification and reasoning about the inner workings of the body contributing to endurance. Findings from this study provided evidence to support the benefits of providing age appropriate but complex coherent biological instruction to children in early childhood settings.

  15. Tobacco as a production platform for biofuel: overexpression of Arabidopsis DGAT and LEC2 genes increases accumulation and shifts the composition of lipids in green biomass.

    Science.gov (United States)

    Andrianov, Vyacheslav; Borisjuk, Nikolai; Pogrebnyak, Natalia; Brinker, Anita; Dixon, Joseph; Spitsin, Sergei; Flynn, John; Matyszczuk, Paulina; Andryszak, Karolina; Laurelli, Marilyn; Golovkin, Maxim; Koprowski, Hilary

    2010-04-01

    When grown for energy production instead for smoking, tobacco can generate a large amount of inexpensive biomass more efficiently than almost any other agricultural crop. Tobacco possesses potent oil biosynthesis machinery and can accumulate up to 40% of seed weight in oil. In this work, we explored two metabolic engineering approaches to enhance the oil content in tobacco green tissues for potential biofuel production. First, an Arabidopsis thaliana gene diacylglycerol acyltransferase (DGAT) coding for a key enzyme in triacylglycerol (TAG) biosynthesis, was expressed in tobacco under the control of a strong ribulose-biphosphate carboxylase small subunit promoter. This modification led to up to a 20-fold increase in TAG accumulation in tobacco leaves and translated into an overall of about a twofold increase in extracted fatty acids (FA) up to 5.8% of dry biomass in Nicotiana tabacum cv Wisconsin, and up to 6% in high-sugar tobacco variety NC-55. Modified tobacco plants also contained elevated amounts of phospholipids. This increase in lipids was accompanied by a shift in the FA composition favourable for their utilization as biodiesel. Second, we expressed in tobacco Arabidopsis gene LEAFY COTYLEDON 2 (LEC2), a master regulator of seed maturation and seed oil storage under the control of an inducible Alc promoter. Stimulation of LEC2 expression in mature tobacco plants by acetaldehyde led to the accumulation of up to 6.8% per dry weight of total extracted FA. The obtained data reveal the potential of metabolically modified plant biomass for the production of biofuel.

  16. The Design and Transformation of Biofundamentals: A Nonsurvey Introductory Evolutionary and Molecular Biology Course.

    Science.gov (United States)

    Klymkowsky, Michael W; Rentsch, Jeremy D; Begovic, Emina; Cooper, Melanie M

    2016-01-01

    Many introductory biology courses amount to superficial surveys of disconnected topics. Often, foundational observations and the concepts derived from them and students' ability to use these ideas appropriately are overlooked, leading to unrealistic expectations and unrecognized learning obstacles. The result can be a focus on memorization at the expense of the development of a meaningful framework within which to consider biological phenomena. About a decade ago, we began a reconsideration of what an introductory course should present to students and the skills they need to master. The original Web-based course's design presaged many of the recommendations of the Vision and Change report; in particular, a focus on social evolutionary mechanisms, stochastic (evolutionary and molecular) processes, and core ideas (cellular continuity, evolutionary homology, molecular interactions, coupled chemical reactions, and molecular machines). Inspired by insights from the Chemistry, Life, the Universe & Everything general chemistry project, we transformed the original Web version into a (freely available) book with a more unified narrative flow and a set of formative assessments delivered through the beSocratic system. We outline how student responses to course materials are guiding future course modifications, in particular a more concerted effort at helping students to construct logical, empirically based arguments, explanations, and models. © 2016 M. W. Klymkowsky et al. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  17. Life on rock. Scaling down biological weathering in a new experimental design at Biosphere-2

    Science.gov (United States)

    Zaharescu, D. G.; Dontsova, K.; Burghelea, C. I.; Chorover, J.; Maier, R.; Perdrial, J. N.

    2012-12-01

    Biological colonization and weathering of bedrock on Earth is a major driver of landscape and ecosystem development, its effects reaching out into other major systems such climate and geochemical cycles of elements. In order to understand how microbe-plant-mycorrhizae communities interact with bedrock in the first phases of mineral weathering we developed a novel experimental design in the Desert Biome at Biosphere-2, University of Arizona (U.S.A). This presentation will focus on the development of the experimental setup. Briefly, six enclosed modules were designed to hold 288 experimental columns that will accommodate 4 rock types and 6 biological treatments. Each module is developed on 3 levels. A lower volume, able to withstand the weight of both, rock material and the rest of the structure, accommodates the sampling elements. A middle volume, houses the experimental columns in a dark chamber. A clear, upper section forms the habitat exposed to sunlight. This volume is completely sealed form exterior and it allows a complete control of its air and water parameters. All modules are connected in parallel with a double air purification system that delivers a permanent air flow. This setup is expected to provide a model experiment, able to test important processes in the interaction rock-life at grain-to- molecular scale.

  18. Multichannel microformulators for massively parallel machine learning and automated design of biological experiments

    Science.gov (United States)

    Wikswo, John; Kolli, Aditya; Shankaran, Harish; Wagoner, Matthew; Mettetal, Jerome; Reiserer, Ronald; Gerken, Gregory; Britt, Clayton; Schaffer, David

    Genetic, proteomic, and metabolic networks describing biological signaling can have 102 to 103 nodes. Transcriptomics and mass spectrometry can quantify 104 different dynamical experimental variables recorded from in vitro experiments with a time resolution approaching 1 s. It is difficult to infer metabolic and signaling models from such massive data sets, and it is unlikely that causality can be determined simply from observed temporal correlations. There is a need to design and apply specific system perturbations, which will be difficult to perform manually with 10 to 102 externally controlled variables. Machine learning and optimal experimental design can select an experiment that best discriminates between multiple conflicting models, but a remaining problem is to control in real time multiple variables in the form of concentrations of growth factors, toxins, nutrients and other signaling molecules. With time-division multiplexing, a microfluidic MicroFormulator (μF) can create in real time complex mixtures of reagents in volumes suitable for biological experiments. Initial 96-channel μF implementations control the exposure profile of cells in a 96-well plate to different temporal profiles of drugs; future experiments will include challenge compounds. Funded in part by AstraZeneca, NIH/NCATS HHSN271201600009C and UH3TR000491, and VIIBRE.

  19. Design of a biologically inspired lower limb exoskeleton for human gait rehabilitation.

    Science.gov (United States)

    Lyu, Mingxing; Chen, Weihai; Ding, Xilun; Wang, Jianhua; Bai, Shaoping; Ren, Huichao

    2016-10-01

    This paper proposes a novel bionic model of the human leg according to the theory of physiology. Based on this model, we present a biologically inspired 3-degree of freedom (DOF) lower limb exoskeleton for human gait rehabilitation, showing that the lower limb exoskeleton is fully compatible with the human knee joint. The exoskeleton has a hybrid serial-parallel kinematic structure consisting of a 1-DOF hip joint module and a 2-DOF knee joint module in the sagittal plane. A planar 2-DOF parallel mechanism is introduced in the design to fully accommodate the motion of the human knee joint, which features not only rotation but also relative sliding. Therefore, the design is consistent with the requirements of bionics. The forward and inverse kinematic analysis is studied and the workspace of the exoskeleton is analyzed. The structural parameters are optimized to obtain a larger workspace. The results using MATLAB-ADAMS co-simulation are shown in this paper to demonstrate the feasibility of our design. A prototype of the exoskeleton is also developed and an experiment performed to verify the kinematic analysis. Compared with existing lower limb exoskeletons, the designed mechanism has a large workspace, while allowing knee joint rotation and small amount of sliding.

  20. Design of a biologically inspired lower limb exoskeleton for human gait rehabilitation

    Science.gov (United States)

    Lyu, Mingxing; Chen, Weihai; Ding, Xilun; Wang, Jianhua; Bai, Shaoping; Ren, Huichao

    2016-10-01

    This paper proposes a novel bionic model of the human leg according to the theory of physiology. Based on this model, we present a biologically inspired 3-degree of freedom (DOF) lower limb exoskeleton for human gait rehabilitation, showing that the lower limb exoskeleton is fully compatible with the human knee joint. The exoskeleton has a hybrid serial-parallel kinematic structure consisting of a 1-DOF hip joint module and a 2-DOF knee joint module in the sagittal plane. A planar 2-DOF parallel mechanism is introduced in the design to fully accommodate the motion of the human knee joint, which features not only rotation but also relative sliding. Therefore, the design is consistent with the requirements of bionics. The forward and inverse kinematic analysis is studied and the workspace of the exoskeleton is analyzed. The structural parameters are optimized to obtain a larger workspace. The results using MATLAB-ADAMS co-simulation are shown in this paper to demonstrate the feasibility of our design. A prototype of the exoskeleton is also developed and an experiment performed to verify the kinematic analysis. Compared with existing lower limb exoskeletons, the designed mechanism has a large workspace, while allowing knee joint rotation and small amount of sliding.

  1. Structure of a designed, right-handed coiled-coil tetramer containing all biological amino acids.

    Science.gov (United States)

    Sales, Mark; Plecs, Joseph J; Holton, James M; Alber, Tom

    2007-10-01

    The previous design of an unprecedented family of two-, three-, and four-helical, right-handed coiled coils utilized nonbiological amino acids to efficiently pack spaces in the oligomer cores. Here we show that a stable, right-handed parallel tetrameric coiled coil, called RH4B, can be designed entirely using biological amino acids. The X-ray crystal structure of RH4B was determined to 1.1 Angstrom resolution using a designed metal binding site to coordinate a single Yb(2+) ion per 33-amino acid polypeptide chain. The resulting experimental phases were particularly accurate, and the experimental electron density map provided an especially clear, unbiased view of the molecule. The RH4B structure closely matched the design, with equivalent core rotamers and an overall root-mean-square deviation for the N-terminal repeat of the tetramer of 0.24 Angstrom. The clarity and resolution of the electron density map, however, revealed alternate rotamers and structural differences between the three sequence repeats in the molecule. These results suggest that the RH4B structure populates an unanticipated variety of structures.

  2. Modeling biology with HDL languages: a first step toward a genetic design automation tool inspired from microelectronics.

    Science.gov (United States)

    Gendrault, Yves; Madec, Morgan; Lallement, Christophe; Haiech, Jacques

    2014-04-01

    Nowadays, synthetic biology is a hot research topic. Each day, progresses are made to improve the complexity of artificial biological functions in order to tend to complex biodevices and biosystems. Up to now, these systems are handmade by bioengineers, which require strong technical skills and leads to nonreusable development. Besides, scientific fields that share the same design approach, such as microelectronics, have already overcome several issues and designers succeed in building extremely complex systems with many evolved functions. On the other hand, in systems engineering and more specifically in microelectronics, the development of the domain has been promoted by both the improvement of technological processes and electronic design automation tools. The work presented in this paper paves the way for the adaptation of microelectronics design tools to synthetic biology. Considering the similarities and differences between the synthetic biology and microelectronics, the milestones of this adaptation are described. The first one concerns the modeling of biological mechanisms. To do so, a new formalism is proposed, based on an extension of the generalized Kirchhoff laws to biology. This way, a description of all biological mechanisms can be made with languages widely used in microelectronics. Our approach is therefore successfully validated on specific examples drawn from the literature.

  3. Differentially regulated splice variants and systems biology analysis of Kaposi's sarcoma-associated herpesvirus-infected lymphatic endothelial cells.

    Science.gov (United States)

    Chang, Ting-Yu; Wu, Yu-Hsuan; Cheng, Cheng-Chung; Wang, Hsei-Wei

    2011-09-01

    Alternative RNA splicing greatly increases proteome diversity, and the possibility of studying genome-wide alternative splicing (AS) events becomes available with the advent of high-throughput genomics tools devoted to this issue. Kaposi's sarcoma associated herpesvirus (KSHV) is the etiological agent of KS, a tumor of lymphatic endothelial cell (LEC) lineage, but little is known about the AS variations induced by KSHV. We analyzed KSHV-controlled AS using high-density microarrays capable of detecting all exons in the human genome. Splicing variants and altered exon-intron usage in infected LEC were found, and these correlated with protein domain modification. The different 3'-UTR used in new transcripts also help isoforms to escape microRNA-mediated surveillance. Exome-level analysis further revealed information that cannot be disclosed using classical gene-level profiling: a significant exon usage difference existed between LEC and CD34(+) precursor cells, and KSHV infection resulted in LEC-to-precursor, dedifferentiation-like exon level reprogramming. Our results demonstrate the application of exon arrays in systems biology research, and suggest the regulatory effects of AS in endothelial cells are far more complex than previously observed. This extra layer of molecular diversity helps to account for various aspects of endothelial biology, KSHV life cycle and disease pathogenesis that until now have been unexplored.

  4. Biological Applications of Designed Hairpin Peptides: As Antimicrobials and as Inhibitors of Amyloidogenesis

    Science.gov (United States)

    Sivanesam, Kalkena

    More than 40 diseases have been associated with the misfolding of peptides (or proteins) that form fibrils with a very specific morphology. These peptides classified as amyloidogenic peptides have been implicated in the development of Alzheimer's Disease, Parkinson's Disease, Type II Diabetes, Hungtinton's Disease etc. To date, these diseases have no cure, only therapies that can ameliorate the symptoms to a degree. Inhibition of the amyloidogenesis of these peptides has been proposed as a possible treatment option. While small molecules have been heavily tested as inhibitors of amyloidogenesis, peptides have emerged as potential inhibitors. In this work, the ability of a set of designed hairpin peptides to inhibit the amyloidogenesis of two different systems, alpha-synuclein (implicated in Parkinson's Disease) and human amylin (implicated in Type II Diabetes) is tested. Using circular dichroism and thioflavin T fluorescence, the ability of these peptides to inhibit amyloidogenesis is tested. The binding loci of these inhibitors to alpha-synuclein are also explored. The use of peptides as antimicrobials on the other hand is not a novel concept. However, most antimicrobial peptides, both natural and designed, rely heavily on covalent stabilizations in order to maintain secondary structure. In this study, non-covalent stabilizations are applied to a couple of natural as well as designed antimicrobials in order to study the effects of secondary structure stabilization on biological activity.

  5. Design of CMOS analog integrated fractional-order circuits applications in medicine and biology

    CERN Document Server

    Tsirimokou, Georgia; Elwakil, Ahmed

    2017-01-01

    This book describes the design and realization of analog fractional-order circuits, which are suitable for on-chip implementation, capable of low-voltage operation and electronic adjustment of their characteristics. The authors provide a brief introduction to fractional-order calculus, followed by design issues for fractional-order circuits of various orders and types. The benefits of this approach are demonstrated with current-mode and voltage-mode filter designs. Electronically tunable emulators of fractional-order capacitors and inductors are presented, where the behavior of the corresponding chips fabricated using the AMS 0.35um CMOS process has been experimentally verified. Applications of fractional-order circuits are demonstrated, including a pre-processing stage suitable for the implementation of the Pan-Tompkins algorithm for detecting the QRS complexes of an electrocardiogram (ECG), a fully tunable implementation of the Cole-Cole model used for the modeling of biological tissues, and a simple, non-i...

  6. Novel study guides for biochemistry meaningful learning in biology: a design-based research

    Directory of Open Access Journals (Sweden)

    Caetano da Costa

    2017-12-01

    Full Text Available To address the usually decontextualized transmission of information in biochemistry teaching, three interventions in a discipline (Metabolism for Biology majors were applied as innovative study guides. We describe the development, application, and evaluation of two study guides, contextualized with a real problem or an integrative view, using broad themes like evolution and metabolic adaptation. In order to evaluate the impact of both interventions on interest, motivation, and learning of the metabolic pathways, a design-based research with cycles of application and assessment was carried out, by means of classroom observation, grade analysis in written exams, and students’ interviews. Analysis and interpretation of the results point to benefits for teaching and learning, with helpful information to guide elaboration and refinement of new teaching materials and to make active learning more meaningful.

  7. Molecular structure descriptors in the computer-aided design of biologically active compounds

    International Nuclear Information System (INIS)

    Raevsky, Oleg A

    1999-01-01

    The current state of description of molecular structure in computer-aided molecular design of biologically active compounds by means of descriptors is analysed. The information contents of descriptors increases in the following sequence: element-level descriptors-structural formulae descriptors-electronic structure descriptors-molecular shape descriptors-intermolecular interaction descriptors. Each subsequent class of descriptors normally covers information contained in the previous-level ones. It is emphasised that it is practically impossible to describe all the features of a molecular structure in terms of any single class of descriptors. It is recommended to optimise the number of descriptors used by means of appropriate statistical procedures and characteristics of structure-property models based on these descriptors. The bibliography includes 371 references.

  8. Design, synthesis, and biological evaluation of achiral analogs of duocarmycin SA.

    Science.gov (United States)

    Daniell, Kristen; Stewart, Michelle; Madsen, Erik; Le, Minh; Handl, Heather; Brooks, Natalie; Kiakos, Konstantinos; Hartley, John A; Lee, Moses

    2005-01-03

    The design, synthesis, as well as biochemical and biological evaluation of two novel achiral analogs of duocarmycin SA (DUMSA), 1 and 2, are described. Like CC-1065 and adozelesin, compounds 1 and 2 covalently reacted with adenine-N3 in AT-rich sequences and led to the formation of DNA strand breaks upon heating. The cytotoxicity of compounds 1 and 2 against human cancer cells (K562, LS174T) was determined using a MTT assay giving IC(50) values in the low nanomolar. Further cytotoxicity screening of compound 2 conducted by the NCI against a panel of 60 different human cancer cell lines indicated that it was particularly active against several solid tumor cells lines derived from the lung, colon, CNS, skin, and breast.

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

    Science.gov (United States)

    Majumder, Sagardip; Liu, Allen P.

    2018-01-01

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

  10. 75 FR 8968 - Draft Guidance for Industry on Adaptive Design Clinical Trials for Drugs and Biologics; Availability

    Science.gov (United States)

    2010-02-26

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0090] Draft Guidance for Industry on Adaptive Design Clinical Trials for Drugs and Biologics; Availability... familiar and less familiar approaches. As more experience is obtained with the less familiar designs...

  11. Natural modifiers of seed longevity in the Arabidopsis mutants abscisic acid insensitive3-5 (abi3-5) and leafy cotyledon1-3 (lec1-3)

    NARCIS (Netherlands)

    Sugliani, M.R.L.; Rajjou, L.; Clerkx, E.J.M.; Koornneef, M.; Soppe, W.J.J.

    2009-01-01

    • Seed longevity is an important trait in many crops and is essential for the success of most land plant species. Current knowledge of its molecular regulation is limited. The Arabidopsis mutants abscisic acid insensitive3-5 (abi3-5) and leafy cotyledon1-3 (lec1-3) have impaired seed maturation and

  12. Methodology for designing and manufacturing complex biologically inspired soft robotic fluidic actuators: prosthetic hand case study.

    Science.gov (United States)

    Thompson-Bean, E; Das, R; McDaid, A

    2016-10-31

    We present a novel methodology for the design and manufacture of complex biologically inspired soft robotic fluidic actuators. The methodology is applied to the design and manufacture of a prosthetic for the hand. Real human hands are scanned to produce a 3D model of a finger, and pneumatic networks are implemented within it to produce a biomimetic bending motion. The finger is then partitioned into material sections, and a genetic algorithm based optimization, using finite element analysis, is employed to discover the optimal material for each section. This is based on two biomimetic performance criteria. Two sets of optimizations using two material sets are performed. Promising optimized material arrangements are fabricated using two techniques to validate the optimization routine, and the fabricated and simulated results are compared. We find that the optimization is successful in producing biomimetic soft robotic fingers and that fabrication of the fingers is possible. Limitations and paths for development are discussed. This methodology can be applied for other fluidic soft robotic devices.

  13. Engineering Bacteria to Search for Specific Concentrations of Molecules by a Systematic Synthetic Biology Design Method.

    Science.gov (United States)

    Tien, Shin-Ming; Hsu, Chih-Yuan; Chen, Bor-Sen

    2016-01-01

    Bacteria navigate environments full of various chemicals to seek favorable places for survival by controlling the flagella's rotation using a complicated signal transduction pathway. By influencing the pathway, bacteria can be engineered to search for specific molecules, which has great potential for application to biomedicine and bioremediation. In this study, genetic circuits were constructed to make bacteria search for a specific molecule at particular concentrations in their environment through a synthetic biology method. In addition, by replacing the "brake component" in the synthetic circuit with some specific sensitivities, the bacteria can be engineered to locate areas containing specific concentrations of the molecule. Measured by the swarm assay qualitatively and microfluidic techniques quantitatively, the characteristics of each "brake component" were identified and represented by a mathematical model. Furthermore, we established another mathematical model to anticipate the characteristics of the "brake component". Based on this model, an abundant component library can be established to provide adequate component selection for different searching conditions without identifying all components individually. Finally, a systematic design procedure was proposed. Following this systematic procedure, one can design a genetic circuit for bacteria to rapidly search for and locate different concentrations of particular molecules by selecting the most adequate "brake component" in the library. Moreover, following simple procedures, one can also establish an exclusive component library suitable for other cultivated environments, promoter systems, or bacterial strains.

  14. Biological shield around the neutral beam injector ducts in the ITER conceptual design

    International Nuclear Information System (INIS)

    Maki, Koichi; Takatsu, Hideyuki; Satoh, Satoshi; Seki, Yasushi

    1994-01-01

    There are gaps between the toroidal field coils and neutral beam injector (NBI) duct wall for the thermal insulator in tokamak reactors such as ITER (International Thermonuclear Experimental Reactor). Neutrons stream through the duct, and some of them penetrate the wall and stream through the gaps. These neutrons activate the materials composing the duct wall, toroidal field coil (TFC) case and cryostat wall surfaces. The dose rate is enhanced just outside the cryostat around the ducts in the reactor room after reactor operation by activation. We investigated the gamma-ray dose rate just outside the cryostat after shutdown due to gamma-rays from activity induced by the neutrons streaming through the gaps. By evaluating the difference between the dose rate in models with and without gaps, we decided whether the thickness of the cryostat as biological shielding is sufficient or not. From these investigations, we recommend a cryostat design suitable for radiation shielding. Dose rates after shutdown at a point just outside the cryostat around the NBI ducts in the model with gaps are two orders larger than those without gaps. The value at this point is approximately 400 mrem h -1 (4 mSv h -1 ), which is two orders larger than the design value for workers to enter the reactor room. In order to reduce the dose rate after shutdown, a method of providing the shielding function of the cryostat is suggested. ((orig.))

  15. Engineering Bacteria to Search for Specific Concentrations of Molecules by a Systematic Synthetic Biology Design Method.

    Directory of Open Access Journals (Sweden)

    Shin-Ming Tien

    Full Text Available Bacteria navigate environments full of various chemicals to seek favorable places for survival by controlling the flagella's rotation using a complicated signal transduction pathway. By influencing the pathway, bacteria can be engineered to search for specific molecules, which has great potential for application to biomedicine and bioremediation. In this study, genetic circuits were constructed to make bacteria search for a specific molecule at particular concentrations in their environment through a synthetic biology method. In addition, by replacing the "brake component" in the synthetic circuit with some specific sensitivities, the bacteria can be engineered to locate areas containing specific concentrations of the molecule. Measured by the swarm assay qualitatively and microfluidic techniques quantitatively, the characteristics of each "brake component" were identified and represented by a mathematical model. Furthermore, we established another mathematical model to anticipate the characteristics of the "brake component". Based on this model, an abundant component library can be established to provide adequate component selection for different searching conditions without identifying all components individually. Finally, a systematic design procedure was proposed. Following this systematic procedure, one can design a genetic circuit for bacteria to rapidly search for and locate different concentrations of particular molecules by selecting the most adequate "brake component" in the library. Moreover, following simple procedures, one can also establish an exclusive component library suitable for other cultivated environments, promoter systems, or bacterial strains.

  16. Evaluation of 320x240 pixel LEC GaAs Schottky barrier X-ray imaging arrays, hybridized to CMOS readout circuit based on charge integration

    CERN Document Server

    Irsigler, R; Alverbro, J; Borglind, J; Froejdh, C; Helander, P; Manolopoulos, S; O'Shea, V; Smith, K

    1999-01-01

    320x240 pixels GaAs Schottky barrier detector arrays were fabricated, hybridized to silicon readout circuits, and subsequently evaluated. The detector chip was based on semi-insulating LEC GaAs material. The square shaped pixel detector elements were of the Schottky barrier type and had a pitch of 38 mu m. The GaAs wafers were thinned down prior to the fabrication of the ohmic back contact. After dicing, the chips were indium bump, flip-chip bonded to CMOS readout circuits based on charge integration, and finally evaluated. A bias voltage between 50 and 100 V was sufficient to operate the detector. Results on I-V characteristics, noise behaviour and response to X-ray radiation are presented. Images of various objects and slit patterns were acquired by using a standard dental imaging X-ray source. The work done was a part of the XIMAGE project financed by the European Community (Brite-Euram). (author)

  17. Sampling designs matching species biology produce accurate and affordable abundance indices.

    Science.gov (United States)

    Harris, Grant; Farley, Sean; Russell, Gareth J; Butler, Matthew J; Selinger, Jeff

    2013-01-01

    Wildlife biologists often use grid-based designs to sample animals and generate abundance estimates. Although sampling in grids is theoretically sound, in application, the method can be logistically difficult and expensive when sampling elusive species inhabiting extensive areas. These factors make it challenging to sample animals and meet the statistical assumption of all individuals having an equal probability of capture. Violating this assumption biases results. Does an alternative exist? Perhaps by sampling only where resources attract animals (i.e., targeted sampling), it would provide accurate abundance estimates more efficiently and affordably. However, biases from this approach would also arise if individuals have an unequal probability of capture, especially if some failed to visit the sampling area. Since most biological programs are resource limited, and acquiring abundance data drives many conservation and management applications, it becomes imperative to identify economical and informative sampling designs. Therefore, we evaluated abundance estimates generated from grid and targeted sampling designs using simulations based on geographic positioning system (GPS) data from 42 Alaskan brown bears (Ursus arctos). Migratory salmon drew brown bears from the wider landscape, concentrating them at anadromous streams. This provided a scenario for testing the targeted approach. Grid and targeted sampling varied by trap amount, location (traps placed randomly, systematically or by expert opinion), and traps stationary or moved between capture sessions. We began by identifying when to sample, and if bears had equal probability of capture. We compared abundance estimates against seven criteria: bias, precision, accuracy, effort, plus encounter rates, and probabilities of capture and recapture. One grid (49 km(2) cells) and one targeted configuration provided the most accurate results. Both placed traps by expert opinion and moved traps between capture sessions

  18. Sampling designs matching species biology produce accurate and affordable abundance indices

    Directory of Open Access Journals (Sweden)

    Grant Harris

    2013-12-01

    Full Text Available Wildlife biologists often use grid-based designs to sample animals and generate abundance estimates. Although sampling in grids is theoretically sound, in application, the method can be logistically difficult and expensive when sampling elusive species inhabiting extensive areas. These factors make it challenging to sample animals and meet the statistical assumption of all individuals having an equal probability of capture. Violating this assumption biases results. Does an alternative exist? Perhaps by sampling only where resources attract animals (i.e., targeted sampling, it would provide accurate abundance estimates more efficiently and affordably. However, biases from this approach would also arise if individuals have an unequal probability of capture, especially if some failed to visit the sampling area. Since most biological programs are resource limited, and acquiring abundance data drives many conservation and management applications, it becomes imperative to identify economical and informative sampling designs. Therefore, we evaluated abundance estimates generated from grid and targeted sampling designs using simulations based on geographic positioning system (GPS data from 42 Alaskan brown bears (Ursus arctos. Migratory salmon drew brown bears from the wider landscape, concentrating them at anadromous streams. This provided a scenario for testing the targeted approach. Grid and targeted sampling varied by trap amount, location (traps placed randomly, systematically or by expert opinion, and traps stationary or moved between capture sessions. We began by identifying when to sample, and if bears had equal probability of capture. We compared abundance estimates against seven criteria: bias, precision, accuracy, effort, plus encounter rates, and probabilities of capture and recapture. One grid (49 km2 cells and one targeted configuration provided the most accurate results. Both placed traps by expert opinion and moved traps between capture

  19. Sampling designs matching species biology produce accurate and affordable abundance indices

    Science.gov (United States)

    Farley, Sean; Russell, Gareth J.; Butler, Matthew J.; Selinger, Jeff

    2013-01-01

    Wildlife biologists often use grid-based designs to sample animals and generate abundance estimates. Although sampling in grids is theoretically sound, in application, the method can be logistically difficult and expensive when sampling elusive species inhabiting extensive areas. These factors make it challenging to sample animals and meet the statistical assumption of all individuals having an equal probability of capture. Violating this assumption biases results. Does an alternative exist? Perhaps by sampling only where resources attract animals (i.e., targeted sampling), it would provide accurate abundance estimates more efficiently and affordably. However, biases from this approach would also arise if individuals have an unequal probability of capture, especially if some failed to visit the sampling area. Since most biological programs are resource limited, and acquiring abundance data drives many conservation and management applications, it becomes imperative to identify economical and informative sampling designs. Therefore, we evaluated abundance estimates generated from grid and targeted sampling designs using simulations based on geographic positioning system (GPS) data from 42 Alaskan brown bears (Ursus arctos). Migratory salmon drew brown bears from the wider landscape, concentrating them at anadromous streams. This provided a scenario for testing the targeted approach. Grid and targeted sampling varied by trap amount, location (traps placed randomly, systematically or by expert opinion), and traps stationary or moved between capture sessions. We began by identifying when to sample, and if bears had equal probability of capture. We compared abundance estimates against seven criteria: bias, precision, accuracy, effort, plus encounter rates, and probabilities of capture and recapture. One grid (49 km2 cells) and one targeted configuration provided the most accurate results. Both placed traps by expert opinion and moved traps between capture sessions, which

  20. An iron-deficient diet stimulates the onset of the hepatitis due to hepatic copper deposition in the Long-Evans Cinnamon (LEC) rat

    Energy Technology Data Exchange (ETDEWEB)

    Sugawara, Naoki; Sugawara, Chieko [Sapporo Medical Univ. (Japan). Dept. of Public Health

    1999-09-01

    To study effects of dietary Cu and Fe levels on the onset of hepatitis in Long-Evans Cinnamon (LEC) rats, female rats (40 days old) were fed a semipurified diet containing 0.1 or 10 mg Cu/kg and 1.5 or 150 mg Fe/kg in a 2 x 2 factorial arrangement for 35 days. At 75 days after birth, LEC rats (+Cu-Fe) fed a Cu-sufficient but Fe-deficient diet (Cu, 10 mg/kg; Fe, 1.5 mg/kg) showed jaundice, with lethargy, anorexia, and malaise. The biochemical variables relating to liver function were significantly increased compared to three other groups, a Cu- and Fe-deficient (-Cu-Fe) group, a Cu-deficient but Fe-sufficient (-Cu+Fe) group, and a Cu and Fe sufficient (+Cu+Fe) group. Furthermore, the +Cu-Fe rat liver showed massive necrosis with huge nuclei. The other three groups presented no biochemical and histological findings of hepatitis. Hepatic Cu and metallothionein concentrations were 289 {+-} 87 (mean {+-} SD) {mu}g/g liver and 8.7 {+-} 1.8 mg/g liver, respectively, in the +Cu-Fe rats. However, in the +Cu+Fe group the values were 196 {+-} 28 {mu}g Cu/g liver and 10.8 {+-} 1.0 mg/g liver. Hepatic Fe deposition was not influenced significantly by the dietary Cu level. The +Cu-Fe group with jaundice showed the highest free Cu concentration in the liver among the four groups, but the hepatic free Fe concentration was similar to those in the -Cu+Fe and +Cu+Fe groups. Our results indicate that an Fe-deficient diet enhances the deposition of hepatic Cu due to increased absorption of Cu from the gastrointestinal tract. This deposition stimulated the onset of hepatitis. (orig.)

  1. Recommendations for designing and conducting veterinary clinical pathology biologic variation studies

    DEFF Research Database (Denmark)

    Freeman, Kathleen P; Baral, Randolph M; Dhand, Navneet K

    2017-01-01

    The recent creation of a veterinary clinical pathology biologic variation website has highlighted the need to provide recommendations for future studies of biologic variation in animals in order to help standardize and improve the quality of published information and to facilitate review......). These recommendations provide a valuable resource for clinicians, laboratorians, and researchers interested in conducting studies of biologic variation and in determining the quality of studies of biologic variation in veterinary laboratory testing....

  2. Structural Biology Insight for the Design of Sub-type Selective Aurora Kinase Inhibitors.

    Science.gov (United States)

    Sarvagalla, Sailu; Coumar, Mohane Selvaraj

    2015-01-01

    Aurora kinase A, B and C, are key regulators of mitosis and are over expressed in many of the human cancers, making them an ideal drug target for cancer chemotherapy. Currently, over a dozen of Aurora kinase inhibitors are in various phases of clinical development. The majority of the inhibitors (VX-680/MK-0457, PHA-739358, CYC116, SNS-314, AMG 900, AT-9283, SCH- 1473759, ABT-348, PF-03814735, R-763/AS-703569, KW-2449 and TAK-901) are pan-selective (isoform non-selective) and few are Aurora A (MLN8054, MLN8237, VX-689/MK5108 and ENMD 2076) and Aurora B (AZD1152 and GSK1070916) sub-type selective. Despite the intensive research efforts in the past decade, no Aurora kinase inhibitor has reached the market. Recent evidence suggests that the sub-type selective Aurora kinase A inhibitor could possess advantages over pan-selective Aurora inhibitors, by avoiding Aurora B mediated neutropenia. However, sub-type selective Aurora kinase A inhibitor design is very challenging due to the similarity in the active site among the isoforms. Structural biology and computational aspects pertaining to the design of Aurora kinase inhibitors were analyzed and found that a possible means to develop sub-type selective inhibitor is by targeting Aurora A specific residues (Leu215, Thr217 and Arg220) or Aurora B specific residues (Arg159, Glu161 and Lys164), near the solvent exposed region of the protein. Particularly, a useful strategy for the design of sub-type selective Aurora A inhibitor could be by targeting Thr217 residue as in the case of MLN8054. Further preclinical and clinical studies with the sub-type selective Aurora inhibitors could help bring them to the market for the treatment of cancer.

  3. Co-design in synthetic biology: a system-level analysis of the development of an environmental sensing device.

    Science.gov (United States)

    Ball, David A; Lux, Matthew W; Graef, Russell R; Peterson, Matthew W; Valenti, Jane D; Dileo, John; Peccoud, Jean

    2010-01-01

    The concept of co-design is common in engineering, where it is necessary, for example, to determine the optimal partitioning between hardware and software of the implementation of a system features. Here we propose to adapt co-design methodologies for synthetic biology. As a test case, we have designed an environmental sensing device that detects the presence of three chemicals, and returns an output only if at least two of the three chemicals are present. We show that the logical operations can be implemented in three different design domains: (1) the transcriptional domain using synthetically designed hybrid promoters, (2) the protein domain using bi-molecular fluorescence complementation, and (3) the fluorescence domain using spectral unmixing and relying on electronic processing. We discuss how these heterogeneous design strategies could be formalized to develop co-design algorithms capable of identifying optimal designs meeting user specifications.

  4. Design, synthesis and biological evaluation of novel hydrogen sulfide releasing capsaicin derivatives.

    Science.gov (United States)

    Gao, Mingxiang; Li, Jinyu; Nie, Cunbin; Song, Beibei; Yan, Lin; Qian, Hai

    2018-05-15

    Capsaicin (CAP), the prototypical TRPV1 agonist, is the major active component in chili peppers with health-promoting benefits. However, its use is limited by the low bioavailability and irritating quality. In this study, for improving the activity of CAP and alleviating its irritating effects, a series of H 2 S-releasing CAPs were designed and synthesized by combining capsaicin and dihydro capsaicin with various hydrogen sulfide donors. The resulting compounds were evaluated their TRPV1 agonist activity, analgesic activity, anticancer activities, H 2 S-releasing ability, and gastric mucosa irritation. Biological evaluation indicated that the most active compound B 9 , containing 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione moiety as H 2 S donor, had better analgesic activity and displayed more potent cytotoxic effects on the test cell lines than the lead compound CAP. Furthermore, the preferred compound, B 9 reduced rat gastric mucosa irritation caused by CAP. Notably, the improved properties of this derivative are associated with its H 2 S-releasing capability. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Design, synthesis, and biological testing of thiosalicylamides as a novel class of calcium channel blockers.

    Science.gov (United States)

    Mehanna, Ahmed S; Kim, Jin Yung

    2005-07-01

    The current research aimed to investigate the importance of the heterocyclic ring system in the structure of the cardiovascular drug diltiazem for its calcium channel blocking activity. The manuscript describes the design, synthesis, and biological testing of a total of 10 S-(p-methoxybenzyl), N-substituted thiosalicylamides as a series of non-cyclic compounds derived from diltiazem's structure. The new compounds maintained all diltiazem pharmacophores except the thiazepine ring system. In vitro evaluation of the new series for calcium channel blocking effects revealed moderate activities with IC50 values in the range of 4.8-56.0 microM. The data suggest that the ring system is not essential for activity; however, its absence leads to a considerable drop of activity relative to that of diltiazem (IC50=0.3 microM). Compounds of the current series showed optimum activity when the aliphatic alkyl chain on the salicylamide nitrogen is part of a piperidine or piperazine ring system substituted at the terminal nitrogen with a benzyl group.

  6. Design, Synthesis, and Biological Evaluation of Vanillin Hydroxamic Acid Derivatives as Novel Peptide Deformylase Inhibitors.

    Science.gov (United States)

    Gao, Jian; Qiu, Shengzhi; Liang, Li; Hao, Zhixiang; Zhou, Qianqian; Wang, Fanfan; Mou, Jie; Lin, Qisi

    2018-01-01

    Infectious disease is increasingly hampering human health, which challenge the discovery of new antibacterial target. Peptide deformylase (PDF), a metalloenzyme responsible for catalyzing the removal of the N-formyl group from nascent proteins, was considered as an important target in antibacterial drug discovery. Reported here are the design, synthesis and biological evaluation of vanillin hydroxamic acid derivatives. Analysis of the structure-activity relationships lead to the discovery of compound 8, which exhibits promising antibacterial activity against Escherichia coli, Staphylococcus aureus, Aspergillus oryzae, and Aspergillus foetidus with the MIC value of 0.32 µg/ml, 0.32 µg/ml, 0.16 µg/ml and 0.16 µg/ml, respectively. Furthermore, molecular docking study was applied to elucidate binding interaction between compound 8 and PDF, which indicate that compound 8 not only shares the same binding pocket with actinonin, but also has a similar binding pattern. In silico pharmacokinetic and toxicity prediction studies also suggested that compound 8 has a relatively high drug score of 0.80, and has no risk of toxicity. Compound 8 might represent a promising scaffold for the further development of novel antibacterial drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Design and characterization of a magnetoelastic sensor for the detection of biological agents

    International Nuclear Information System (INIS)

    Shen Wen; Mathison, Leslie C; Chin, Bryan A; Petrenko, Valery A

    2010-01-01

    This paper presents the design and development of a free-standing, magnetoelastic biosensor. The detection principle is presented and various resonance characteristics of the sensor are discussed. Experimental measurements of the sensor resonance frequencies agree with theoretical predictions. The influence of the external magnetic field on the resonance behaviour of the sensor was studied and the optimum dc magnetic fields for best sensitivity in air and in water solutions for 2000 x 400 x 15 μm (2 mm) sensors and 1000 x 200 x 15 μm (1 mm) size sensors were determined to be 75 Oe and 38 Oe, respectively. Both theoretical prediction and experimental results show that smaller sensors have greater mass sensitivity and can theoretically detect mass as small as one biological spore. The sensor platform was immobilized with JRB7 phages for specific, in vitro detection of B. anthracis spores. Real-time detection of spores suspended in water was demonstrated using a flowing system. The 1 mm and 2 mm sensors were found to have a detection limit of 10 4 spores ml -1 and 10 5 spores ml -1 , respectively.

  8. Biological engineering applications of feedforward neural networks designed and parameterized by genetic algorithms.

    Science.gov (United States)

    Ferentinos, Konstantinos P

    2005-09-01

    Two neural network (NN) applications in the field of biological engineering are developed, designed and parameterized by an evolutionary method based on the evolutionary process of genetic algorithms. The developed systems are a fault detection NN model and a predictive modeling NN system. An indirect or 'weak specification' representation was used for the encoding of NN topologies and training parameters into genes of the genetic algorithm (GA). Some a priori knowledge of the demands in network topology for specific application cases is required by this approach, so that the infinite search space of the problem is limited to some reasonable degree. Both one-hidden-layer and two-hidden-layer network architectures were explored by the GA. Except for the network architecture, each gene of the GA also encoded the type of activation functions in both hidden and output nodes of the NN and the type of minimization algorithm that was used by the backpropagation algorithm for the training of the NN. Both models achieved satisfactory performance, while the GA system proved to be a powerful tool that can successfully replace the problematic trial-and-error approach that is usually used for these tasks.

  9. Novel aminopyrimidinyl benzimidazoles as potentially antimicrobial agents: Design, synthesis and biological evaluation.

    Science.gov (United States)

    Liu, Han-Bo; Gao, Wei-Wei; Tangadanchu, Vijai Kumar Reddy; Zhou, Cheng-He; Geng, Rong-Xia

    2018-01-01

    A series of novel aminopyrimidinyl benzimidazoles as potentially antimicrobial agents were designed, synthesized and characterized by IR, NMR and HRMS spectra. The biological evaluation in vitro revealed that some of the target compounds exerted good antibacterial and antifungal activity in comparison with the reference drugs. Noticeably, compound 7d could effectively inhibit the growth of A. flavus, E. coli DH52 and MRSA with MIC values of 1, 1 and 8 μg/mL, respectively. Further studies revealed that pyrimidine derivative 7d could exhibit bactericidal mode of action against both Gram positive (S. aureus and MRSA) and Gram negative (P. aeruginosa) bacteria. The active molecule 7d showed low cell toxicity and did not obviously trigger the development of resistance in bacteria even after 16 passages. Furthermore, compound 7d was able to beneficially regulate reactive oxygen species (ROS) generation for an excellent safety profile. Molecular docking study revealed that compound 7d could bind with DNA gyrase by the formation of hydrogen bonds. The preliminary exploration for antimicrobial mechanism disclosed that compound 7d could effectively intercalate into calf thymus DNA to form a steady supramolecular complex, which might further block DNA replication to exert the powerful bioactivities. The binding investigation of compound 7d with human serum albumins (HSA) revealed that this molecule could be effectively transported by HSA. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  10. Methods for open innovation on a genome-design platform associating scientific, commercial, and educational communities in synthetic biology.

    Science.gov (United States)

    Toyoda, Tetsuro

    2011-01-01

    Synthetic biology requires both engineering efficiency and compliance with safety guidelines and ethics. Focusing on the rational construction of biological systems based on engineering principles, synthetic biology depends on a genome-design platform to explore the combinations of multiple biological components or BIO bricks for quickly producing innovative devices. This chapter explains the differences among various platform models and details a methodology for promoting open innovation within the scope of the statutory exemption of patent laws. The detailed platform adopts a centralized evaluation model (CEM), computer-aided design (CAD) bricks, and a freemium model. It is also important for the platform to support the legal aspects of copyrights as well as patent and safety guidelines because intellectual work including DNA sequences designed rationally by human intelligence is basically copyrightable. An informational platform with high traceability, transparency, auditability, and security is required for copyright proof, safety compliance, and incentive management for open innovation in synthetic biology. GenoCon, which we have organized and explained here, is a competition-styled, open-innovation method involving worldwide participants from scientific, commercial, and educational communities that aims to improve the designs of genomic sequences that confer a desired function on an organism. Using only a Web browser, a participating contributor proposes a design expressed with CAD bricks that generate a relevant DNA sequence, which is then experimentally and intensively evaluated by the GenoCon organizers. The CAD bricks that comprise programs and databases as a Semantic Web are developed, executed, shared, reused, and well stocked on the secure Semantic Web platform called the Scientists' Networking System or SciNetS/SciNeS, based on which a CEM research center for synthetic biology and open innovation should be established. Copyright © 2011 Elsevier Inc

  11. Traditional Versus Online Biology Courses: Connecting Course Design and Student Learning in an Online Setting

    OpenAIRE

    Biel, Rachel; Brame, Cynthia J.

    2016-01-01

    Online courses are a large and growing part of the undergraduate education landscape, but many biology instructors are skeptical about the effectiveness of online instruction. We reviewed studies comparing the effectiveness of online and face-to-face (F2F) undergraduate biology courses. Five studies compared student performance in multiple course sections at community colleges, while eight were smaller scale and compared student performance in particular biology courses at a variety of types ...

  12. Design of SGLT2 Inhibitors for the Treatment of Type 2 Diabetes: A History Driven by Biology to Chemistry.

    Science.gov (United States)

    Cai, Wenqing; Jiang, Linlin; Xie, Yafei; Liu, Yuqiang; Liu, Wei; Zhao, Guilong

    2015-01-01

    A brief history of the design of sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors is reviewed. The design of O-glucoside SGLT2 inhibitors by structural modification of phlorizin, a naturally occurring O-glucoside, in the early stage was a process mainly driven by biology with anticipation of improving SGLT2/SGLT1 selectivity and increasing metabolic stability. Discovery of dapagliflozin, a pioneering C-glucoside SGLT2 inhibitor developed by Bristol-Myers Squibb, represents an important milestone in this history. In the second stage, the design of C-glycoside SGLT2 inhibitors by modifications of the aglycone and glucose moiety of dapagliflozin, an original structural template for almost all C-glycoside SGLT2 inhibitors, was mainly driven by synthetic organic chemistry due to the challenge of designing dapagliflozin derivatives that are patentable, biologically active and synthetically accessible. Structure-activity relationships (SAR) of the SGLT2 inhibitors are also discussed.

  13. Recontextualising Cellular Respiration : Designing an learning-and-teaching strategy for developing biological concepts as flexible tools

    NARCIS (Netherlands)

    Wierdsma, M.D.M.

    2012-01-01

    This thesis reports on a design-research study on recontextualising biological concepts. The term ‘recontextualising’ is based in socio-cultural activity theory and was proposed by van Oers in 1998 as a change of perspective on the idea of knowledge-transfer. Within this view concepts are tools to

  14. How to Generate Understanding of the Scientific Process in Introductory Biology: A Student-Designed Laboratory Exercise on Yeast Fermentation

    Science.gov (United States)

    Collins, Linda T.; Bell, Rebekah P.

    2004-01-01

    Heavy faculty teaching loads and limited funds biology teachers designed certain objectives in order to increase the understandability of the subject matter of the laboratory exercises they write. In relation to these objectives an old "cookbook" laboratory exercise on yeast fermentation is introduced which involve students asking questions,…

  15. Recommendations for designing and conducting veterinary clinical pathology biologic variation studies.

    Science.gov (United States)

    Freeman, Kathleen P; Baral, Randolph M; Dhand, Navneet K; Nielsen, Søren Saxmose; Jensen, Asger L

    2017-06-01

    The recent creation of a veterinary clinical pathology biologic variation website has highlighted the need to provide recommendations for future studies of biologic variation in animals in order to help standardize and improve the quality of published information and to facilitate review and selection of publications as standard references. The following recommendations are provided in the format and order commonly found in veterinary publications. A checklist is provided to aid in planning, implementing, and evaluating veterinary studies on biologic variation (Appendix S1). These recommendations provide a valuable resource for clinicians, laboratorians, and researchers interested in conducting studies of biologic variation and in determining the quality of studies of biologic variation in veterinary laboratory testing. © 2017 American Society for Veterinary Clinical Pathology.

  16. Novel Study Guides for Biochemistry Meaningful Learning in Biology: a Design-Based Research

    Directory of Open Access Journals (Sweden)

    Costa, C ; Galembeck, E. Costa, C ; Galembeck, E.

    2017-07-01

    Full Text Available One of the difficulties for biochemistry learning is the persistence of traditional teaching methods, based on transmission and memorization of abstract and detailed information, usually in a decontextualized way. Such scenario results in surface learning and content reproduction. In order to address these problems, three interventions in a discipline (Metabolism for Biology majors were applied, in the form of innovative teaching tools (study guides. OBJECTIVES: The main goal is to evaluate the impact of these interventions on interest, motivation, and learning of the metabolic pathways. MATERIALS AND METHODS: We describe the development, application, and evaluation of two study guides – one created from a problem used as a contextual connection for glycogen metabolism study and another embedding an integrative view based on glutamate metabolism. Both materials were guided by broad themes like evolution, metabolic adaptation, and comparative biochemistry. The development of the study guides combined submicroscopic (molecular and macroscopic (body, environment levels, aiming to motivate reading and discussion. A design-based research with cycles of application and assessment was carried out, by means of classroom observation, grade analysis in written exams, and students’ interviews. RESULTS AND DISCUSSION: In general, based on in-class student feedback to professors and to the researcher in the interviews, the study guides arouse curiosity and fostered peer discussion. Final average grades indicate a good global performance in all proposed activities. Whole data from study guides’ application in classroom evidenced their impact on interest, motivation, and learning. The strategy of developing problem or integrative situation linking molecular (micro and contextual (macro levels were helpful to foster critical thinking and to value topics of scientific literacy. CONCLUSIONS: Analysis and interpretation of the results point to benefits for

  17. The impact of technetium-99m-radiopharmaceuticals' design on their biological behavior

    International Nuclear Information System (INIS)

    Jankovic, D.Lj.; Djokic, D.Dj. . E-mail address of corresponding author: drinaj@vin.bg.ac.yu; Jankovic, D.)

    2005-01-01

    The coordination has a great and not always predictable impact on the in-vivo behaviour of the small molecule into which the technetium-bearing chelate units is integrated. The different valence state of technetium in the complexes with some ligands changes the properties of these complexes, such as physico-chemical parameters and biological behaviour. The change of their biological behaviour has a great impact on quality of imaging study and on radiation dose to the patient. The results of the labelling of DPD and EHIDA with 99mTc(I) and their biological behaviour, in comparison with the same one for 99mTc(III)-DPD and 99mTc(III)-EHIDA complexes, confirmed that different oxidation state of 99mTc make possible forming variety of complexes with quite a different and unexpected biological behaviour. (author)

  18. Design and Fabrication of Slotted Multimode Interference Devices for Chemical and Biological Sensing

    Directory of Open Access Journals (Sweden)

    M. Mayeh

    2009-01-01

    Full Text Available We present optical sensors based on slotted multimode interference waveguides. The sensor can be tuned to highest sensitivity in the refractive index ranges necessary to detect protein-based molecules or other water-soluble chemical or biological materials. The material of choice is low-loss silicon oxynitride (SiON which is highly stable to the reactivity with biological agents and processing chemicals. Sensors made with this technology are suited to high volume manufacturing.

  19. On extracting design principles from biology: II. Case study—the effect of knee direction on bipedal robot running efficiency

    International Nuclear Information System (INIS)

    Haberland, M; Kim, S

    2015-01-01

    Comparing the leg of an ostrich to that of a human suggests an important question to legged robot designers: should a robot's leg joint bend in the direction of running (‘forwards’) or opposite (‘backwards’)? Biological studies cannot answer this question for engineers due to significant differences between the biological and engineering domains. Instead, we investigated the inherent effect of joint bending direction on bipedal robot running efficiency by comparing energetically optimal gaits of a wide variety of robot designs sampled at random from a design space. We found that the great majority of robot designs have several locally optimal gaits with the knee bending backwards that are more efficient than the most efficient gait with the knee bending forwards. The most efficient backwards gaits do not exhibit lower touchdown losses than the most efficient forward gaits; rather, the improved efficiency of backwards gaits stems from lower torque and reduced motion at the hip. The reduced hip use of backwards gaits is enabled by the ability of the backwards knee, acting alone, to (1) propel the robot upwards and forwards simultaneously and (2) lift and protract the foot simultaneously. In the absence of other information, designers interested in building efficient bipedal robots with two-segment legs driven by electric motors should design the knee to bend backwards rather than forwards. Compared to common practices for choosing robot knee direction, application of this principle would have a strong tendency to improve robot efficiency and save design resources. (paper)

  20. Cross-cultural adaptation of the Posttraumatic Stress Disorder Checklist 5 (PCL-5 and Life Events Checklist 5 (LEC-5 for the Brazilian context

    Directory of Open Access Journals (Sweden)

    Eduardo de Paula Lima

    Full Text Available Abstract Objective: To describe the process of cross-cultural adaptation of the Posttraumatic Stress Disorder Checklist 5 (PCL-5 and the Life Events Checklist 5 (LEC-5 for the Brazilian sociolinguistic context. Method: The adaptation process sought to establish conceptual, semantic, and operational equivalence between the original items of the questionnaire and their translated versions, following standardized protocols. Initially, two researchers translated the original version of the scale into Brazilian Portuguese. Next, a native English speaker performed the back-translation. Quantitative and qualitative criteria were used to evaluate the intelligibility of items. Five specialists compared the original and translated versions and assessed the degree of equivalence between them in terms of semantic, idiomatic, cultural and conceptual aspects. The degree of agreement between the specialists was measured using the content validity coefficient (CVC. Finally, 28 volunteers from the target population were interviewed in order to assess their level of comprehension of the items. Results: CVCs for items from both scales were satisfactory for all criteria. The mean comprehension scores were above the cutoff point established. Overall, the results showed that the adapted versions' items had adequate rates of equivalence in terms of concepts and semantics. Conclusions: The translation and adaptation processes were successful for both scales, resulting in versions that are not only equivalent to the originals, but are also intelligible for the population at large.

  1. Design, modeling and control of a pneumatically actuated manipulator inspired by biological continuum structures

    International Nuclear Information System (INIS)

    Kang, Rongjie; Zheng Tianjiang; Guglielmino, Emanuele; Caldwell, Darwin G; Branson, David T

    2013-01-01

    Biological tentacles, such as octopus arms, have entirely flexible structures and virtually infinite degrees of freedom (DOF) that allow for elongation, shortening and bending at any point along the arm length. The amazing dexterity of biological tentacles has driven the growing implementation of continuum manipulators in robotic systems. This paper presents a pneumatic manipulator inspired by biological continuum structures in some of their key features and functions, such as continuum morphology, intrinsic compliance and stereotyped motions with hyper redundant DOF. The kinematics and dynamics of the manipulator are formulated and identified, and a hierarchical controller taking inspiration from the structure of an octopus nervous system is used to relate desired stereotyped motions to individual actuator inputs. Simulations and experiments are carried out to validate the model and prototype where good agreement was found between the two. (paper)

  2. Development of a rechargeable optical hydrogen peroxide sensor - sensor design and biological application

    DEFF Research Database (Denmark)

    Koren, Klaus; Jensen, Peter Østrup; Kühl, Michael

    2016-01-01

    and readout strategy, H2O2 can be measured with high spatial (∼500 μm) and temporal (∼30 s) resolution. The sensor has a broad applicability both in complex environmental and biomedical systems, as demonstrated by (i) H2O2 concentration profile measurements in natural photosynthetic biofilms under light....... Quantifying H2O2 within biological samples is challenging and often not possible. Here we present a quasi-reversible fiber-optic sensor capable of measuring H2O2 concentrations ranging from 1-100 μM within different biological samples. Based on a Prussian blue/white redox cycle and a simple sensor recharging...

  3. Developing optimal input design strategies in cancer systems biology with applications to microfluidic device engineering

    NARCIS (Netherlands)

    Menolascina, F.; Bellomo, D.; Maiwald, T.; Bevilacqua, V.; Ciminelli, C.; Paradiso, A.; Tommasi, S.

    2009-01-01

    Background: Mechanistic models are becoming more and more popular in Systems Biology; identification and control of models underlying biochemical pathways of interest in oncology is a primary goal in this field. Unfortunately the scarce availability of data still limits our understanding of the

  4. Exploring Cystic Fibrosis Using Bioinformatics Tools: A Module Designed for the Freshman Biology Course

    Science.gov (United States)

    Zhang, Xiaorong

    2011-01-01

    We incorporated a bioinformatics component into the freshman biology course that allows students to explore cystic fibrosis (CF), a common genetic disorder, using bioinformatics tools and skills. Students learn about CF through searching genetic databases, analyzing genetic sequences, and observing the three-dimensional structures of proteins…

  5. Towards an optimal experimental design for N2O model calibration during biological nitrogen removal

    DEFF Research Database (Denmark)

    Domingo Felez, Carlos; Valverde Pérez, Borja; Plósz, Benedek G.

    Process models describing nitrous oxide (N2O) production during biological nitrogen removal allow for the development of mitigation strategies of this potent greenhouse gas. N2O is an intermediate of nitrogen removal, hence its prediction is negatively affected by the uncertainty associated to it...... of strategies to minimize the carbon footprint of wastewater treatment plants....

  6. Mixed-Methods Design in Biology Education Research: Approach and Uses

    Science.gov (United States)

    Warfa, Abdi-Rizak M.

    2016-01-01

    Educational research often requires mixing different research methodologies to strengthen findings, better contextualize or explain results, or minimize the weaknesses of a single method. This article provides practical guidelines on how to conduct such research in biology education, with a focus on mixed-methods research (MMR) that uses both…

  7. 50 CFR 216.191 - Designation of Offshore Biologically Important Marine Mammal Areas.

    Science.gov (United States)

    2010-10-01

    ...) Detailed information on the biology of marine mammals within the area, including estimated population size... Important Marine Mammal Areas. 216.191 Section 216.191 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS...

  8. Exploring matter through photons and neutrons: from biological molecules to designer materials

    International Nuclear Information System (INIS)

    Chidambaram, R.; Hosur, M.V.; Ramanadham, M.; Godwal, B.K.

    2000-01-01

    Understanding structure-property relationships of naturally occurring materials has been the aim of scientific research for centuries. The discovery of short wavelength x-rays and neutrons in the 20th century provided a means of studying molecular structure. The methodology of x-ray and neutron diffraction has been successfully applied to determine structures of molecules across disciplines of physics, chemistry, biology, biochemistry and medicine. Typical applications in physics include study of phase transformations, elasticity measurements, magnetic structure, surface scattering etc. In chemistry, the applications have ranged from routine structure determinations of reaction intermediates or natural products to refinement of quantum chemical parameters of atomic and molecular charge densities. The science of crystallography has had a profound effect on the disciplines of biology and medicine. A whole new discipline and industry was created when the structure of DNA was discovered through x-ray diffraction

  9. Design, Synthesis and Biological Evaluation of Benzohydrazide Derivatives Containing Dihydropyrazoles as Potential EGFR Kinase Inhibitors

    Directory of Open Access Journals (Sweden)

    Hai-Chao Wang

    2016-08-01

    Full Text Available A series of novel benzohydrazide derivatives containing dihydropyrazoles have been synthesized as potential epidermal growth factor receptor (EGFR kinase inhibitors and their biological activities as potential antiproliferative agents have been evaluated. Among these compounds, compound H20 exhibited the most potent antiproliferative activity against four cancer cell line variants (A549, MCF-7, HeLa, HepG2 with IC50 values of 0.46, 0.29, 0.15 and 0.21 μM respectively, which showed the most potent EGFR inhibition activities (IC50 = 0.08 μM for EGFR. Molecular modeling simulation studies were performed in order to predict the biological activity and activity relationship (SAR of these benzohydrazide derivatives. These results suggested that compound H20 may be a promising anticancer agent.

  10. Design and development of modular DNA assembly tools for Multigene Engineering and Synthetic Biology in Plants

    OpenAIRE

    Sarrión Perdigones, Manuel Alejandro

    2014-01-01

    The post-genomics era has put at the disposal of modern plant breeders an endless list of genetic building blocks for the design of new biotechnological crops. After a first wave of single-gene transgenic with controversial public acceptance, genomic information and technology is paving the way for increasingly complex designs based in multiple gene engineering. Those designs aiming at the production of inexpensive health-promoting compounds are most likely to be welcomed by consumers. In thi...

  11. A Photo-triggered and photo-calibrated nitric oxide donor: Rational design, spectral characterizations, and biological applications.

    Science.gov (United States)

    He, Haihong; Liu, Yuxin; Zhou, Zhongneng; Guo, Chunlei; Wang, Hong-Yin; Wang, Zhuang; Wang, Xueli; Zhang, Ziqian; Wu, Fu-Gen; Wang, Haolu; Chen, Daijie; Yang, Dahai; Liang, Xiaowen; Chen, Jinquan; Zhou, Shengmin; Liang, Xin; Qian, Xuhong; Yang, Youjun

    2018-04-27

    Nitric oxide (NO) donors are valuable tools to probe the profound implications of NO in health and disease. The elusive nature of NO bio-relevance has largely limited the use of spontaneous NO donors and promoted the development of next generation NO donors, whose NO release is not only stimulated by a trigger, but also readily monitored via a judiciously built-in self-calibration mechanism. Light is without a doubt the most sensitive, versatile and biocompatible method of choice for both triggering and monitoring, for applications in complex biological matrices. Herein, we designed and synthesized an N-nitroso rhodamine derivative (NOD560) as a photo-triggered and photo-calibrated NO donor to address this need. NOD560 is essentially non-fluorescent. Upon irradiation by green light (532 nm), it efficiently release NO and a rhodamine dye, the dramatic fluorescence turn-on from which could be harnessed to conveniently monitor the localization, flux, and dose of NO release. The potentials of NOD560 for in vitro biological applications were also exemplified in in vitro biological models, i.e. mesenchymal stem cell (MSC) migration suppression. NOD560 is expected to complement the existing NO donors and find widespread applications in chemical biological studies. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. G‐LoSA: An efficient computational tool for local structure‐centric biological studies and drug design

    Science.gov (United States)

    2016-01-01

    Abstract Molecular recognition by protein mostly occurs in a local region on the protein surface. Thus, an efficient computational method for accurate characterization of protein local structural conservation is necessary to better understand biology and drug design. We present a novel local structure alignment tool, G‐LoSA. G‐LoSA aligns protein local structures in a sequence order independent way and provides a GA‐score, a chemical feature‐based and size‐independent structure similarity score. Our benchmark validation shows the robust performance of G‐LoSA to the local structures of diverse sizes and characteristics, demonstrating its universal applicability to local structure‐centric comparative biology studies. In particular, G‐LoSA is highly effective in detecting conserved local regions on the entire surface of a given protein. In addition, the applications of G‐LoSA to identifying template ligands and predicting ligand and protein binding sites illustrate its strong potential for computer‐aided drug design. We hope that G‐LoSA can be a useful computational method for exploring interesting biological problems through large‐scale comparison of protein local structures and facilitating drug discovery research and development. G‐LoSA is freely available to academic users at http://im.compbio.ku.edu/GLoSA/. PMID:26813336

  13. G-LoSA: An efficient computational tool for local structure-centric biological studies and drug design.

    Science.gov (United States)

    Lee, Hui Sun; Im, Wonpil

    2016-04-01

    Molecular recognition by protein mostly occurs in a local region on the protein surface. Thus, an efficient computational method for accurate characterization of protein local structural conservation is necessary to better understand biology and drug design. We present a novel local structure alignment tool, G-LoSA. G-LoSA aligns protein local structures in a sequence order independent way and provides a GA-score, a chemical feature-based and size-independent structure similarity score. Our benchmark validation shows the robust performance of G-LoSA to the local structures of diverse sizes and characteristics, demonstrating its universal applicability to local structure-centric comparative biology studies. In particular, G-LoSA is highly effective in detecting conserved local regions on the entire surface of a given protein. In addition, the applications of G-LoSA to identifying template ligands and predicting ligand and protein binding sites illustrate its strong potential for computer-aided drug design. We hope that G-LoSA can be a useful computational method for exploring interesting biological problems through large-scale comparison of protein local structures and facilitating drug discovery research and development. G-LoSA is freely available to academic users at http://im.compbio.ku.edu/GLoSA/. © 2016 The Protein Society.

  14. Puzzles in modern biology. I. Male sterility, failure reveals design [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Steven A. Frank

    2016-09-01

    Full Text Available Many human males produce dysfunctional sperm. Various plants frequently abort pollen. Hybrid matings often produce sterile males. Widespread male sterility is puzzling. Natural selection prunes reproductive failure. Puzzling failure implies something that we do not understand about how organisms are designed. Solving the puzzle reveals the hidden processes of design.

  15. Design-Based Learning for Biology: Genetic Engineering Experience Improves Understanding of Gene Expression

    Science.gov (United States)

    Ellefson, Michelle R.; Brinker, Rebecca A.; Vernacchio, Vincent J.; Schunn, Christian D.

    2008-01-01

    Gene expression is a difficult topic for students to learn and comprehend, at least partially because it involves various biochemical structures and processes occurring at the microscopic level. Designer Bacteria, a design-based learning (DBL) unit for high-school students, applies principles of DBL to the teaching of gene expression. Throughout…

  16. CASTOR BEAN AND SUNFLOWER INTERCROPPING SYSTEMS IN ROW ARRANGEMENT: BIOLOGICAL EFFICIENCY

    Directory of Open Access Journals (Sweden)

    Ciro de Miranda Pinto

    2012-07-01

    Full Text Available An experiment field was carried in the agricultural seasons 2008, 2009 and 2010, with aim of studying the response of castorbean (Ricinus communis L. intercropping with sunflower (Helianthus annus L. in row arrangement in the dryland farming conditions. In addition, it was evaluated the biological efficiency of plants in intercropping systems.The design used in the experiment was randomized block with seven treatement and four replications. The treatments were represented by rows of castor oil (Ma and sunflower (Gi listed below: 1Ma:1Gi; 1Ma:2Gi; 1Ma:3Gi; 2Ma:2Gi; 2Ma:3Gi; castor and sunflower in the monoculture. The efficiency of intercropping was measured by LER, ATER, LEC, average between LER and ATER, SPI and CoR. The grain yield of castor bean and sunflower were reduced in intercropped row arrangements. The row arrangement 1Ma:2Gi showed the smallest reduction of average productivity of castor beans and sunflower in the evaluation period of the experiment. The castor bean was the dominant crop in relation to sunflower.

  17. Control Structure Design of an Innovative Enhanced Biological Nutrient Recovery Activated Sludge System Coupled with a Photobioreactor

    DEFF Research Database (Denmark)

    Valverde Perez, Borja; Fuentes-Martínez, José Manuel; Flores Alsina, Xavier

    2015-01-01

    The TRENS system is a train of biological units designed for resource recovery from wastewater. It is a sequence of a modified enhanced biological phosphorus removal and recovery system (EBP2R) coupled with a photobioreactor (PBR). The bacteria-based system constructs an optimal culture media...... for the downstream algae cultivation. In this work, we present a control strategy to ensure an optimal nutrient balance to feed to the PBR, so the grown algal suspension is suitable for fertigation (irrigation and fertilization of agricultural crops). The system is able to recover up to 75% of the influent load......, while keeping an optimal N-to-P ratio of 16 in the influent to the PBR. The system is tested under different scenarios, where the influent quality is disturbed following a step change. The control system is able to reject most of the disturbances. However, when the P-recovery is limited by the bacteria...

  18. Modern Biology

    OpenAIRE

    ALEKSIC, Branko

    2014-01-01

    The purpose of this course is to learn the philosophy, principles, and techniques of modern biology. The course is particularly designed for those who have not learned biology previously or whose major is other than biology, and who may think that they do not need to know any biology at all. The topics are covered in a rather general, overview manner, but certain level of diligence in grasping concepts and memorizing the terminology is expected.

  19. The Design of a Molecular Assembly Line Based on Biological Molecules

    Science.gov (United States)

    2003-06-01

    parenthesis in figure 1.8 is a bi-stable toggle switch. Introduction: Molecular assembly lines O=P-O- O O HOH H0P-0- O -O- 4 Polymerase HO H--- O HHO ...sample. Therefore, the samples are self-consistent. From here on, the calculated temperature based on FAM emission MNSowmm" RF Biology: Results and...irradiation for one hour. Figure 2.11 shows the fluorescence spectra of FAM emission (4 scans averaged over 200 seconds) in a 300MHz field. The increased

  20. A Biologically Inspired Energy-Efficient Duty Cycle Design Method for Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Jie Zhou

    2017-01-01

    Full Text Available The recent success of emerging wireless sensor networks technology has encouraged researchers to develop new energy-efficient duty cycle design algorithm in this field. The energy-efficient duty cycle design problem is a typical NP-hard combinatorial optimization problem. In this paper, we investigate an improved elite immune evolutionary algorithm (IEIEA strategy to optimize energy-efficient duty cycle design scheme and monitored area jointly to enhance the network lifetimes. Simulation results show that the network lifetime of the proposed IEIEA method increased compared to the other two methods, which means that the proposed method improves the full coverage constraints.

  1. Streamlined Total Synthesis of Trioxacarcins and Its Application to the Design, Synthesis, and Biological Evaluation of Analogues Thereof. Discovery of Simpler Designed and Potent Trioxacarcin Analogues.

    Science.gov (United States)

    Nicolaou, K C; Chen, Pengxi; Zhu, Shugao; Cai, Quan; Erande, Rohan D; Li, Ruofan; Sun, Hongbao; Pulukuri, Kiran Kumar; Rigol, Stephan; Aujay, Monette; Sandoval, Joseph; Gavrilyuk, Julia

    2017-11-01

    A streamlined total synthesis of the naturally occurring antitumor agents trioxacarcins is described, along with its application to the construction of a series of designed analogues of these complex natural products. Biological evaluation of the synthesized compounds revealed a number of highly potent, and yet structurally simpler, compounds that are effective against certain cancer cell lines, including a drug-resistant line. A novel one-step synthesis of anthraquinones and chloro anthraquinones from simple ketone precursors and phenylselenyl chloride is also described. The reported work, featuring novel chemistry and cascade reactions, has potential applications in cancer therapy, including targeted approaches as in antibody-drug conjugates.

  2. Development of Design Tools for the Optimization of Biologically Based Control Systems

    Data.gov (United States)

    National Aeronautics and Space Administration — I plan to develop software that aids in the design of biomimetic control systems by optimizing the properties of the system in order to produce the desired output....

  3. A review of active learning approaches to experimental design for uncovering biological networks

    Science.gov (United States)

    2017-01-01

    Various types of biological knowledge describe networks of interactions among elementary entities. For example, transcriptional regulatory networks consist of interactions among proteins and genes. Current knowledge about the exact structure of such networks is highly incomplete, and laboratory experiments that manipulate the entities involved are conducted to test hypotheses about these networks. In recent years, various automated approaches to experiment selection have been proposed. Many of these approaches can be characterized as active machine learning algorithms. Active learning is an iterative process in which a model is learned from data, hypotheses are generated from the model to propose informative experiments, and the experiments yield new data that is used to update the model. This review describes the various models, experiment selection strategies, validation techniques, and successful applications described in the literature; highlights common themes and notable distinctions among methods; and identifies likely directions of future research and open problems in the area. PMID:28570593

  4. Design and biological activity of β-sheet breaker peptide conjugates

    International Nuclear Information System (INIS)

    Rocha, Sandra; Cardoso, Isabel; Boerner, Hans; Pereira, Maria Carmo; Saraiva, Maria Joao; Coelho, Manuel

    2009-01-01

    The sequence LPFFD (iAβ 5 ) prevents amyloid-β peptide (Aβ) fibrillogenesis and neurotoxicity, hallmarks of Alzheimer's disease (AD), as previously demonstrated. In this study iAβ 5 was covalently linked to poly(ethylene glycol) (PEG) and the activity of conjugates was assessed and compared to the activity of the peptide alone by in vitro studies. The conjugates were characterized by MALDI-TOF. Competition binding assays established that conjugates retained the ability to bind Aβ with similar strength as iAβ 5 . Transmission electron microscopy analysis showed that iAβ 5 conjugates inhibited amyloid fibril formation, which is in agreement with binding properties observed for the conjugates towards Aβ. The conjugates were also able to prevent amyloid-induced cell death, as evaluated by activation of caspase 3. These results demonstrated that the biological activity of iAβ 5 is not affected by the pegylation process.

  5. 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

  6. Design, synthesis and biological evaluation of Erythrina alkaloid analogues as neuronal nicotinic acetylcholine receptor antagonists

    DEFF Research Database (Denmark)

    Crestey, François; Jensen, Anders A.; Borch, Morten

    2013-01-01

    The synthesis of a new series of Erythrina alkaloid analogues and their pharmacological characterization at various nicotine acetylcholine receptor (nAChR) subtypes are described. The compounds were designed to be simplified analogues of aromatic erythrinanes with the aim of obtaining subtype...

  7. Design, synthesis and biological activity of novel peptidyl benzyl ketone FVIIa inhibitors

    DEFF Research Database (Denmark)

    Storgaard, Morten; Henriksen, Signe Teuber; Zaragoza, Florencio

    2011-01-01

    Herein is described the synthesis of a novel class of peptidyl FVIIa inhibitors having a C-terminal benzyl ketone group. This class is designed to be potentially suitable as stabilization agents of liquid formulations of rFVIIa, which is a serine protease used for the treatment of hemophilia...

  8. Design, Synthesis and Biological Evaluation of Novel Benzothiazole Derivatives as Selective PI3Kβ Inhibitors

    Directory of Open Access Journals (Sweden)

    Shuang Cao

    2016-07-01

    Full Text Available A novel series of PI3Kβ (Phosphatidylinositol-3-kinases beta subunit inhibitors with the structure of benzothiazole scaffold have been designed and synthesized. All the compounds have been evaluated for inhibitory activities against PI3Kα, β, γ, δ and mTOR (Mammalian target of rapamycin. Two superior compounds have been further evaluated for the IC50 values against PI3Ks/mTOR. The most promising compound 11 displays excellent anti-proliferative activity and selectivity in multiple cancer cell lines, especially in the prostate cancer cell line. Docking studies indicate the morpholine group in 2-position of benzothiazole is necessary for the potent antitumor activity, which confirms our design is reasonable.

  9. Computer-assisted Biology Learning Materials: Designing and Developing an Interactive CD on Spermatogenesis

    Science.gov (United States)

    Haviz, M.

    2018-04-01

    The purpose of this article is to design and develop an interactive CD on spermatogenesis. This is a research and development. Procedure of development is making an outline of media program, making flowchart, making story board, gathering of materials, programming and finishing. The quantitative data obtained were analyzed by descriptive statistics. Qualitative data obtained were analyzed with Miles and Huberman techniques. The instrument used is a validation sheet. The result of CD design with a Macro flash MX program shows there are 17 slides generated. This prototype obtained a valid value after a self-review technique with many revisions, especially on sound and programming. This finding suggests that process-oriented spermatogenesis can be audio-visualized into a more comprehensive form of learning media. But this interactive CD product needs further testing to determine consistency and resistance to revisions.

  10. Design optimization under uncertainties of a mesoscale implant in biological tissues using a probabilistic learning algorithm

    Science.gov (United States)

    Soize, C.

    2017-11-01

    This paper deals with the optimal design of a titanium mesoscale implant in a cortical bone for which the apparent elasticity tensor is modeled by a non-Gaussian random field at mesoscale, which has been experimentally identified. The external applied forces are also random. The design parameters are geometrical dimensions related to the geometry of the implant. The stochastic elastostatic boundary value problem is discretized by the finite element method. The objective function and the constraints are related to normal, shear, and von Mises stresses inside the cortical bone. The constrained nonconvex optimization problem in presence of uncertainties is solved by using a probabilistic learning algorithm that allows for considerably reducing the numerical cost with respect to the classical approaches.

  11. Biological neural networks as model systems for designing future parallel processing computers

    Science.gov (United States)

    Ross, Muriel D.

    1991-01-01

    One of the more interesting debates of the present day centers on whether human intelligence can be simulated by computer. The author works under the premise that neurons individually are not smart at all. Rather, they are physical units which are impinged upon continuously by other matter that influences the direction of voltage shifts across the units membranes. It is only the action of a great many neurons, billions in the case of the human nervous system, that intelligent behavior emerges. What is required to understand even the simplest neural system is painstaking analysis, bit by bit, of the architecture and the physiological functioning of its various parts. The biological neural network studied, the vestibular utricular and saccular maculas of the inner ear, are among the most simple of the mammalian neural networks to understand and model. While there is still a long way to go to understand even this most simple neural network in sufficient detail for extrapolation to computers and robots, a start was made. Moreover, the insights obtained and the technologies developed help advance the understanding of the more complex neural networks that underlie human intelligence.

  12. Narrow Bandwidth Top-Emitting OLEDs Designed for Rhodamine 6G Excitation in Biological Sensing Applications

    Directory of Open Access Journals (Sweden)

    Matthias Jahnel

    2015-11-01

    Full Text Available Organic light emitting diodes (OLED are promising candidates offering in optical sensor applications to detect different gas compositions and excitable optical marker groups in chemical and biological processes. They enable attractive solutions for monitoring the gas phase composition of e.g., dissolved molecular oxygen (O2 species in bio reactors or excitation of fluorescent markers. In this work, we investigate different OLED devices for biomedical applications to excite the fluorescent dye rhodamine 6G (R6G. The OLED devices are built in top emission geometry comprising a distributed Bragg reflector (DBR acting as optical mirror. The OLED is optimized to provide a very narrow emission characteristic to excite the R6G at 530 nm wavelength and enabling the possibility to minimize the optical crosstalk between the OLED electroluminescence and the fluorescence of R6G. The DBR includes a thin film encapsulation and enables the narrowing of the spectral emission band depending on the number of DBR pairs. The comparison between optical simulation data and experimental results exhibits good agreement and proves process stability.

  13. Design of a High-Throughput Biological Crystallography Beamline for Superconducting Wiggler

    International Nuclear Information System (INIS)

    Tseng, P.C.; Chang, C.H.; Fung, H.S.; Ma, C.I.; Huang, L.J.; Jean, Y.C.; Song, Y.F.; Huang, Y.S.; Tsang, K.L.; Chen, C.T.

    2004-01-01

    We are constructing a high-throughput biological crystallography beamline BL13B, which utilizes the radiation generated from a 3.2 Tesla, 32-pole superconducting multipole wiggler, for multi-wavelength anomalous diffraction (MAD), single-wavelength anomalous diffraction (SAD), and other related experiments. This beamline is a standard double crystal monochromator (DCM) x-ray beamline equipped with a collimating mirror (CM) and a focusing mirror (FM). Both the CM and FM are one meter long and made of Si substrate, and the CM is side-cooled by water. Based on detailed thermal analysis, liquid nitrogen (LN2) cooling for both crystals of the DCM has been adopted to optimize the energy resolution and photon beam throughput. This beamline will deliver, through a 100 μm diameter pinhole, photon flux of greater than 1011 photons/sec in the energy range from 6.5 keV to 19 keV, which is comparable to existing protein crystallography beamlines from bending magnet source at high energy storage rings

  14. Designing mental health interventions informed by child development and human biology theory: a social ecology intervention for child soldiers in Nepal.

    Science.gov (United States)

    Kohrt, Brandon A; Jordans, Mark J D; Koirala, Suraj; Worthman, Carol M

    2015-01-01

    The anthropological study of human biology, health, and child development provides a model with potential to address the gap in population-wide mental health interventions. Four key concepts from human biology can inform public mental health interventions: life history theory and tradeoffs, redundancy and plurality of pathways, cascades and multiplier effects in biological systems, and proximate feedback systems. A public mental health intervention for former child soldiers in Nepal is used to illustrate the role of these concepts in intervention design and evaluation. Future directions and recommendations for applying human biology theory in pursuit of public mental health interventions are discussed. © 2014 Wiley Periodicals, Inc.

  15. Designing deoxidation inhibiting encapsulation of metal oxide nanostructures for fluidic and biological applications

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, Moumita, E-mail: ghoshiisc@gmail.com [Instrumentation and Applied Physics, Indian Institute of Science, Bangalore 560012 (India); Centre for Nano Science and Engineering, Indian Institute of Science, Bangalore 560012 (India); IV. Institute of Physics, Georg-August-Universität-Göttingen, Friedrich-Hund-Platz 1, 37077 Göttingen (Germany); III. Institute of Physics – Biophysics and Complex Systems, Georg-August-Universität-Göttingen, Friedrich-Hund-Platz 1, 37077 Göttingen (Germany); Ghosh, Siddharth [III. Institute of Physics – Biophysics and Complex Systems, Georg-August-Universität-Göttingen, Friedrich-Hund-Platz 1, 37077 Göttingen (Germany); Seibt, Michael [IV. Institute of Physics, Georg-August-Universität-Göttingen, Friedrich-Hund-Platz 1, 37077 Göttingen (Germany); Schaap, Iwan A.T. [III. Institute of Physics – Biophysics and Complex Systems, Georg-August-Universität-Göttingen, Friedrich-Hund-Platz 1, 37077 Göttingen (Germany); Institute of Biological Chemistry, Biophysics and Bioengineering, Heriot-Watt University, Edinburgh EH14 4AS (United Kingdom); Schmidt, Christoph F. [III. Institute of Physics – Biophysics and Complex Systems, Georg-August-Universität-Göttingen, Friedrich-Hund-Platz 1, 37077 Göttingen (Germany); Mohan Rao, G. [Instrumentation and Applied Physics, Indian Institute of Science, Bangalore 560012 (India)

    2016-12-30

    Graphical abstract: To retain atomic structure and morphology of ZnO nanostructures (caused by deoxidation of ZnO) in water/bio-fluids, we propose and demonstrate a robust and inexpensive encapsulation technique using bio-compatible non-ionic surfactant. - Highlights: • Aqueous solutions of ZnO nanorods with and without surfactant are prepared. • With time ZnO nanorods show structural deterioration in different aqueous solutions. • Crystallinity of ZnO nanorods in absence of aqueous solution remain unaffected. • Encapsulation of bio-compatible surfactant in alchohol avoid ZnO deoxidation. • Crystallinity and structure of ZnO nanorods after encapsulation remain unaffected. - Abstract: Due to their photoluminescence, metal oxide nanostructures such as ZnO nanostructures are promising candidates in biomedical imaging, drug delivery and bio-sensing. To apply them as label for bio-imaging, it is important to study their structural stability in a bio-fluidic environment. We have explored the effect of water, the main constituent of biological solutions, on ZnO nanostructures with scanning electron microscopy (SEM) and photoluminescence (PL) studies which show ZnO nanorod degeneration in water. In addition, we propose and investigate a robust and inexpensive method to encapsulate these nanostructures (without structural degradation) using bio-compatible non-ionic surfactant in non-aqueous medium, which was not reported earlier. This new finding is an immediate interest to the broad audience of researchers working in biophysics, sensing and actuation, drug delivery, food and cosmetics technology, etc.

  16. Substituted 3-Benzylcoumarins as Allosteric MEK1 Inhibitors: Design, Synthesis and Biological Evaluation as Antiviral Agents

    Directory of Open Access Journals (Sweden)

    Ping Xu

    2013-05-01

    Full Text Available In order to find novel antiviral agents, a series of allosteric MEK1 inhibitors were designed and synthesized. Based on docking results, multiple optimizations were made on the coumarin scaffold. Some of the derivatives showed excellent MEK1 binding affinity in the appropriate enzymatic assays and displayed obvious inhibitory effects on the ERK pathway in a cellular assay. These compounds also significantly inhibited virus (EV71 replication in HEK293 and RD cells. Several compounds showed potential as agents for the treatment of viral infective diseases, with the most potent compound 18 showing an IC50 value of 54.57 nM in the MEK1 binding assay.

  17. Identification of anthranilamide derivatives as potential factor Xa inhibitors: drug design, synthesis and biological evaluation.

    Science.gov (United States)

    Xing, Junhao; Yang, Lingyun; Li, Hui; Li, Qing; Zhao, Leilei; Wang, Xinning; Zhang, Yuan; Zhou, Muxing; Zhou, Jinpei; Zhang, Huibin

    2015-05-05

    The coagulation enzyme factor Xa (fXa) plays a crucial role in the blood coagulation cascade. In this study, three-dimensional fragment based drug design (FBDD) combined with structure-based pharmacophore (SBP) model and structural consensus docking were employed to identify novel fXa inhibitors. After a multi-stage virtual screening (VS) workflow, two hit compounds 3780 and 319 having persistent high performance were identified. Then, these two hit compounds and several analogs were synthesized and screened for in-vitro inhibition of fXa. The experimental data showed that most of the designed compounds displayed significant in vitro potency against fXa. Among them, compound 9b displayed the greatest in vitro potency against fXa with the IC50 value of 23 nM and excellent selectivity versus thrombin (IC50 = 40 μM). Moreover, the prolongation of the prothrombin time (PT) was measured for compound 9b to evaluate its in vitro anticoagulant activity. As a result, compound 9b exhibited pronounced anticoagulant activity with the 2 × PT value of 8.7 μM. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  18. Computational Biology Tools for Identifying Specific Ligand Binding Residues for Novel Agrochemical and Drug Design.

    Science.gov (United States)

    Neshich, Izabella Agostinho Pena; Nishimura, Leticia; de Moraes, Fabio Rogerio; Salim, Jose Augusto; Villalta-Romero, Fabian; Borro, Luiz; Yano, Inacio Henrique; Mazoni, Ivan; Tasic, Ljubica; Jardine, Jose Gilberto; Neshich, Goran

    2015-01-01

    The term "agrochemicals" is used in its generic form to represent a spectrum of pesticides, such as insecticides, fungicides or bactericides. They contain active components designed for optimized pest management and control, therefore allowing for economically sound and labor efficient agricultural production. A "drug" on the other side is a term that is used for compounds designed for controlling human diseases. Although drugs are subjected to much more severe testing and regulation procedures before reaching the market, they might contain exactly the same active ingredient as certain agrochemicals, what is the case described in present work, showing how a small chemical compound might be used to control pathogenicity of Gram negative bacteria Xylella fastidiosa which devastates citrus plantations, as well as for control of, for example, meningitis in humans. It is also clear that so far the production of new agrochemicals is not benefiting as much from the in silico new chemical compound identification/discovery as pharmaceutical production. Rational drug design crucially depends on detailed knowledge of structural information about the receptor (target protein) and the ligand (drug/agrochemical). The interaction between the two molecules is the subject of analysis that aims to understand relationship between structure and function, mainly deciphering some fundamental elements of the nanoenvironment where the interaction occurs. In this work we will emphasize the role of understanding nanoenvironmental factors that guide recognition and interaction of target protein and its function modifier, an agrochemical or a drug. The repertoire of nanoenvironment descriptors is used for two selected and specific cases we have approached in order to offer a technological solution for some very important problems that needs special attention in agriculture: elimination of pathogenicity of a bacterium which is attacking citrus plants and formulation of a new fungicide. Finally

  19. Teaching Assistant Professional Development in Biology: Designed for and Driven by Multidimensional Data

    Science.gov (United States)

    Long, Tammy M.; Ebert-May, Diane

    2014-01-01

    Graduate teaching assistants (TAs) are increasingly responsible for instruction in undergraduate science, technology, engineering, and mathematics (STEM) courses. Various professional development (PD) programs have been developed and implemented to prepare TAs for this role, but data about effectiveness are lacking and are derived almost exclusively from self-reported surveys. In this study, we describe the design of a reformed PD (RPD) model and apply Kirkpatrick's Evaluation Framework to evaluate multiple outcomes of TA PD before, during, and after implementing RPD. This framework allows evaluation that includes both direct measures and self-reported data. In RPD, TAs created and aligned learning objectives and assessments and incorporated more learner-centered instructional practices in their teaching. However, these data are inconsistent with TAs’ self-reported perceptions about RPD and suggest that single measures are insufficient to evaluate TA PD programs. PMID:26086654

  20. Seco-B-Ring Steroidal Dienynes with Aromatic D Ring: Design, Synthesis and Biological Evaluation

    Directory of Open Access Journals (Sweden)

    Marcin Szybinski

    2017-10-01

    Full Text Available Continuing our structure-activity studies on the vitamin D analogs with the altered intercyclic seco-B-ring fragment, we designed compounds possessing dienyne system conjugated with the benzene D ring. Analysis of the literature data and the docking experiments seemed to indicate that the target compounds could mimic the ligands with a good affinity to the vitamin D receptor (VDR. Multi-step synthesis of the C/D-ring building block of the tetralone structure was achieved and its enol triflate was coupled with the known A-ring fragments, possessing conjugated enyne moiety, using Sonogashira protocol. The structures of the final products were confirmed by NMR, UV and mass spectroscopy. Their binding affinities for the full-length human VDR were determined and it was established that compound substituted at C-2 with exomethylene group showed significant binding to the receptor. This analog was also able to induce monocytic differentiation of HL-60 cells.

  1. Design, Synthesis and Biological Evaluation of C(6-Modified Celastrol Derivatives as Potential Antitumor Agents

    Directory of Open Access Journals (Sweden)

    Kaiyong Tang

    2014-07-01

    Full Text Available New six C6-celastrol derivatives were designed, synthesized, and evaluated for their in vitro cytotoxic activities against nine human cancer cell lines (BGC-823, H4, Bel7402, H522, Colo 205, HepG2 and MDA-MB-468. The results showed that most of the compounds displayed potent inhibition against BGC823, H4, and Bel7402, with IC50s of 1.84–0.39 μM. The best compound NST001A was tested in an in vivo antitumor assay on nude mice bearing Colo 205 xenografts, and showed significant inhibition of tumor growth at low concentrations. Therefore, celastrol C-6 derivatives are potential drug candidates for treating cancer.

  2. Design, synthesis, and biological evaluation of the first podophyllotoxin analogues as potential vascular-disrupting agents.

    Science.gov (United States)

    Labruère, Raphaël; Gautier, Benoît; Testud, Marlène; Seguin, Johanne; Lenoir, Christine; Desbène-Finck, Stéphanie; Helissey, Philippe; Garbay, Christiane; Chabot, Guy G; Vidal, Michel; Giorgi-Renault, Sylviane

    2010-12-03

    We designed and synthesized two novel series of azapodophyllotoxin analogues as potential antivascular agents. A linker was inserted between the trimethoxyphenyl ring E and the tetracyclic ABCD moiety of the 4-aza-1,2-didehydropodophyllotoxins. In the first series, the linker enables free rotation between the two moieties; in the second series, conformational restriction of the E nucleus was considered. We have identified several new compounds with inhibitory activity toward tubulin polymerization similar to that of CA-4 and colchicine, while displaying low cytotoxic activity against normal and/or cancer cells. An aminologue and a methylenic analogue were shown to disrupt endothelial cell cords on Matrigel at subtoxic concentrations, and an original assay of drug washout allowed us to demonstrate the rapid reversibility of this effect. These two new analogues are promising leads for the development of vascular-disrupting agents in the podophyllotoxin series.

  3. Structural Biology and Molecular Modeling in the Design of Novel DPP-4 Inhibitors

    Science.gov (United States)

    Scapin, Giovanna

    Inhibition of dipeptidyl peptidase IV (DPP-4) is a promising new approach for the treatment of type 2 diabetes. DPP-4 is the enzyme responsible for inactivating the incretin hormones glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP), two hormones that play important roles in glucose homeostasis. The potent, orally bioavailable and highly selective small molecule DPP-4 inhibitor sitagliptin has been approved by the FDA as novel drug for the treatment of type 2 diabetes. The comparison between the binding mode of sitagliptin (a β-amino acid) and that of a second class of inhibitors (α-amino acid-based) initially led to the successful identification and design of structurally diverse and highly potent DPP-4 inhibitors. Further analysis of the crystal structure of sitagliptin bound to DPP-4 suggested that the central β-amino butanoyl moiety could be replaced by a rigid group. This was confirmed by molecular modeling, and the resulting cyclohexylamine analogs were synthesized and found to be potent DPP-4 inhibitors. However, the triazolopyrazine was predicted to be distorted in order to fit in the binding pocket, and the crystal structure showed that multiple conformations exist for this moiety. Additional molecular modeling studies were then used to improve potency of the cyclohexylamine series. In addition, a 3-D QSAR method was used to gain insight for reducing off-target DPP-8/9 activities. Novel compounds were thus synthesized and found to be potent DPP-4 inhibitors. Two compounds in particular were designed to be highly selective against off-target "DPP-4 Activity- and/or Structure Homologues" (DASH) enzymes while maintaining potency against DPP-4.

  4. Multi-objective optimization of a compact pressurized water nuclear reactor computational model for biological shielding design using innovative materials

    Energy Technology Data Exchange (ETDEWEB)

    Tunes, M.A., E-mail: matheus.tunes@usp.br [Department of Metallurgical and Materials Engineering, Escola Politécnica da Universidade de São Paulo, Av. Prof. Mello Moraes, 2463 – CEP 05508 – 030 São Paulo (Brazil); Oliveira, C.R.E. de, E-mail: cassiano@unm.edu [Department of Nuclear Engineering, The University of New Mexico, Farris Engineering Center, 221, Albuquerque, NM 87131-1070 (United States); Schön, C.G., E-mail: schoen@usp.br [Department of Metallurgical and Materials Engineering, Escola Politécnica da Universidade de São Paulo, Av. Prof. Mello Moraes, 2463 – CEP 05508 – 030 São Paulo (Brazil)

    2017-03-15

    Highlights: • Use of two n-γ transport codes leads to optimized model of compact nuclear reactor. • It was possible to safely reduce both weight and volume of the biological shielding. • Best configuration obtained by using new composites for both γ and n attenuation. - Abstract: The aim of the present work is to develop a computational model of a compact pressurized water nuclear reactor (PWR) to investigate the use of innovative materials to enhance the biological shielding effectiveness. Two radiation transport codes were used: the first one – MCNP – for the PWR design and the GEM/EVENT to simulate (in a 1D slab) the behavior of several materials and shielding thickness on gamma and neutron radiation. Additionally MATLAB Optimization Toolbox was used to provide new geometric configurations of the slab aiming at reducing the volume and weight of the walls by means of a cost/objective function. It is demonstrated in the reactor model that the dose rate outside biological shielding has been reduced by one order of magnitude for the optimized model compared with the initial configuration. Volume and weight of the shielding walls were also reduced. The results indicated that one-dimensional deterministic code to reach an optimized geometry and test materials, combined with a three-dimensional model of a compact nuclear reactor in a stochastic code, is a fast and efficient procedure to test shielding performance and optimization before the experimental assessment. A major outcome of this research is that composite materials (ECOMASS 2150TU96) may replace (with advantages) traditional shielding materials without jeopardizing the nuclear power plant safety assurance.

  5. Extended N-Arylsulfonylindoles as 5-HT6 Receptor Antagonists: Design, Synthesis & Biological Evaluation

    Directory of Open Access Journals (Sweden)

    Gonzalo Vera

    2016-08-01

    Full Text Available Based on a known pharmacophore model for 5-HT6 receptor antagonists, a series of novel extended derivatives of the N-arylsulfonyindole scaffold were designed and identified as a new class of 5-HT6 receptor modulators. Eight of the compounds exhibited moderate to high binding affinities and displayed antagonist profile in 5-HT6 receptor functional assays. Compounds 2-(4-(2-methoxyphenylpiperazin-1-yl-1-(1-tosyl-1H-indol-3-ylethanol (4b, 1-(1-(4-iodophenylsulfonyl-1H-indol-3-yl-2-(4-(2-methoxyphenylpiperazin-1-ylethanol (4g and 2-(4-(2-methoxyphenylpiperazin-1-yl-1-(1-(naphthalen-1-ylsulfonyl-1H-indol-3-ylethanol (4j showed the best binding affinity (4b pKi = 7.87; 4g pKi = 7.73; 4j pKi = 7.83. Additionally, compound 4j was identified as a highly potent antagonist (IC50 = 32 nM in calcium mobilisation functional assay.

  6. Design, synthesis, and biological evaluation of prenylated chalcones as 5-LOX inhibitors.

    Science.gov (United States)

    Reddy, Nimmanapalli P; Aparoy, Polamarasetty; Reddy, T Chandra Mohan; Achari, Chandrani; Sridhar, P Ramu; Reddanna, Pallu

    2010-08-15

    Ten novel mono- and di-O-prenylated chalcone derivatives were designed on the basis of a homology derived molecular model of 5-lipoxygenase (5-LOX). The compounds were docked into 5-LOX active site and the binding characteristics were quantified using LUDI. To verify our theoretical assumption, the molecules were synthesized and tested for their 5-LOX inhibitory activities. The synthesis was carried out by Claisen-Schmidt condensation reaction of mono- and di-O-prenylated acetophenones with appropriate aldehydes. 5-LOX in vitro inhibition assay showed higher potency of di-O-prenylated chalcones than their mono-O-prenylated chalcone analogs. Compound 5e exhibited good inhibition with an IC(50) at 4 microM. The overall trend for the binding energies calculated and LUDI score was in good qualitative agreement with the experimental data. Further, the compound 5e showed potent anti-proliferative effects (GI(50) at 9 microM) on breast cancer cell line, MCF-7. Copyright 2010 Elsevier Ltd. All rights reserved.

  7. Omics Meets Biology: Application to the Design and Preclinical Assessment of Antivenoms

    Directory of Open Access Journals (Sweden)

    Juan J. Calvete

    2014-12-01

    Full Text Available Snakebite envenoming represents a neglected tropical disease that has a heavy public health impact worldwide, mostly affecting poor people involved in agricultural activities in Africa, Asia, Latin America and Oceania. A key issue that complicates the treatment of snakebite envenomings is the poor availability of the only validated treatment for this disease, antivenoms. Antivenoms can be an efficacious treatment for snakebite envenoming, provided they are safe, effective, affordable, accessible and administered appropriately. The shortage of antivenoms in various regions, particularly in Sub-Saharan Africa and some parts of Asia, can be significantly alleviated by optimizing the use of current antivenoms and by the generation of novel polyspecific antivenoms having a wide spectrum of efficacy. Complementing preclinical testing of antivenom efficacy using in vivo and in vitro functional neutralization assays, developments in venomics and antivenomics are likely to revolutionize the design and preclinical assessment of antivenoms by being able to test new antivenom preparations and to predict their paraspecific neutralization to the level of species-specific toxins.

  8. Design, synthesis and antibreast cancer MCF-7 cells biological evaluation of heterocyclic analogs of resveratrol.

    Science.gov (United States)

    Du, Cheng; Dong, Ming-Hui; Ren, Yu-Jie; Jin, Lu; Xu, Cheng

    2017-09-01

    A new series of resveratrol heterocyclic analogs (4a-m) were designed and synthesized, and their inhibitiory effects on MCF-7 cells were evaluated to investigate structure-activity relationship. The effects of these analogs on human breast cancer MCF-7 cells were also determined. Results showed that MCF-7 cells could be inhibited more potently by these analogs than by resveratrol (IC 50  = 80.0 μM). Among the analogs, compounds 4c, 4e, and 4k showed a significantly higher activity (IC 50  = 42.7, 48.1, and 43.4 μM) than resveratrol. Furthermore, the derivatives without additional heterocyclic structure in the 4'-OH position exhibited a more potent activity than that with addition heterocyclic structure. In addition, docking simulation was performed to adequately position compound 4c in a human F 1 -ATPase active site to determine a probable binding model. These heterocyclic analogs could be effective candidates for the chemoprevention of human breast cancer.

  9. "Solvent-in-salt" systems for design of new materials in chemistry, biology and energy research.

    Science.gov (United States)

    Azov, Vladimir A; Egorova, Ksenia S; Seitkalieva, Marina M; Kashin, Alexey S; Ananikov, Valentine P

    2018-02-21

    Inorganic and organic "solvent-in-salt" (SIS) systems have been known for decades but have attracted significant attention only recently. Molten salt hydrates/solvates have been successfully employed as non-flammable, benign electrolytes in rechargeable lithium-ion batteries leading to a revolution in battery development and design. SIS with organic components (for example, ionic liquids containing small amounts of water) demonstrate remarkable thermal stability and tunability, and present a class of admittedly safer electrolytes, in comparison with traditional organic solvents. Water molecules tend to form nano- and microstructures (droplets and channel networks) in ionic media impacting their heterogeneity. Such microscale domains can be employed as microreactors for chemical and enzymatic synthesis. In this review, we address known SIS systems and discuss their composition, structure, properties and dynamics. Special attention is paid to the current and potential applications of inorganic and organic SIS systems in energy research, chemistry and biochemistry. A separate section of this review is dedicated to experimental methods of SIS investigation, which is crucial for the development of this field.

  10. Design, synthesis, and biological characterization of metabolically stable selective androgen receptor modulators.

    Science.gov (United States)

    Marhefka, Craig A; Gao, Wenqing; Chung, Kiwon; Kim, Juhyun; He, Yali; Yin, Donghua; Bohl, Casey; Dalton, James T; Miller, Duane D

    2004-02-12

    A series of nonsteroidal ligands were synthesized as second-generation agonists for the androgen receptor (AR). These ligands were designed to eliminate metabolic sites identified in one of our first-generation AR agonists, which was inactive in vivo due to its rapid metabolism to inactive constituents. The binding affinity of these compounds was evaluated using AR isolated from rat ventral prostate. These second-generation compounds bound the AR in a high affinity and stereoselective manner, with K(i) values ranging from about 4 to 130 nM. The ability of these ligands to stimulate AR-mediated transcriptional activation was examined in cells transfected with the human AR and a hormone-dependent luciferase reporter gene. Although some compounds were unable to stimulate AR-mediated transcription, several demonstrated activity similar to that of dihydrotestosterone (DHT, an endogenous steroidal ligand for the AR). We also evaluated the in vivo pharmacologic activity of selected compounds in castrated male rats. Three compounds were identified as selective androgen receptor modulators (SARMs), exhibiting significant anabolic activity while having only moderate to minimal androgenic activity in vivo.

  11. Design and construction of a first-generation high-throughput integrated robotic molecular biology platform for bioenergy applications.

    Science.gov (United States)

    Hughes, Stephen R; Butt, Tauseef R; Bartolett, Scott; Riedmuller, Steven B; Farrelly, Philip

    2011-08-01

    The molecular biological techniques for plasmid-based assembly and cloning of gene open reading frames are essential for elucidating the function of the proteins encoded by the genes. High-throughput integrated robotic molecular biology platforms that have the capacity to rapidly clone and express heterologous gene open reading frames in bacteria and yeast and to screen large numbers of expressed proteins for optimized function are an important technology for improving microbial strains for biofuel production. The process involves the production of full-length complementary DNA libraries as a source of plasmid-based clones to express the desired proteins in active form for determination of their functions. Proteins that were identified by high-throughput screening as having desired characteristics are overexpressed in microbes to enable them to perform functions that will allow more cost-effective and sustainable production of biofuels. Because the plasmid libraries are composed of several thousand unique genes, automation of the process is essential. This review describes the design and implementation of an automated integrated programmable robotic workcell capable of producing complementary DNA libraries, colony picking, isolating plasmid DNA, transforming yeast and bacteria, expressing protein, and performing appropriate functional assays. These operations will allow tailoring microbial strains to use renewable feedstocks for production of biofuels, bioderived chemicals, fertilizers, and other coproducts for profitable and sustainable biorefineries. Published by Elsevier Inc.

  12. Design and validation of a dynamic cell-culture system for bone biology research and exogenous tissue-engineering applications.

    Science.gov (United States)

    Allori, Alexander C; Davidson, Edward H; Reformat, Derek D; Sailon, Alexander M; Freeman, James; Vaughan, Adam; Wootton, David; Clark, Elizabeth; Ricci, John L; Warren, Stephen M

    2016-10-01

    Bone lacunocanalicular fluid flow ensures chemotransportation and provides a mechanical stimulus to cells. Traditional static cell-culture methods are ill-suited to study the intricacies of bone biology because they ignore the three-dimensionality of meaningful cellular networks and the lacunocanalicular system; furthermore, reliance on diffusion alone for nutrient supply and waste product removal effectively limits scaffolds to 2-3 mm thickness. In this project, a flow-perfusion system was custom-designed to overcome these limitations: eight adaptable chambers housed cylindrical cell-seeded scaffolds measuring 12 or 24 mm in diameter and 1-10 mm in thickness. The porous scaffolds were manufactured using a three-dimensional (3D) periodic microprinting process and were composed of hydroxyapatite/tricalcium phosphate with variable thicknesses, strut sizes, pore sizes and structural configurations. A multi-channel peristaltic pump drew medium from parallel reservoirs and perfused it through each scaffold at a programmable rate. Hermetically sealed valves permitted sampling or replacement of medium. A gas-permeable membrane allowed for gas exchange. Tubing was selected to withstand continuous perfusion for > 2 months without leakage. Computational modelling was performed to assess the adequacy of oxygen supply and the range of fluid shear stress in the bioreactor-scaffold system, using 12 × 6 mm scaffolds, and these models suggested scaffold design modifications that improved oxygen delivery while enhancing physiological shear stress. This system may prove useful in studying complex 3D bone biology and in developing strategies for engineering thick 3D bone constructs. Copyright © 2013 John Wiley & Sons, Ltd. Copyright © 2013 John Wiley & Sons, Ltd.

  13. 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.

  14. Design of a multi-dopamine-modified polymer ligand optimally suited for interfacing magnetic nanoparticles with biological systems.

    Science.gov (United States)

    Wang, Wentao; Ji, Xin; Na, Hyon Bin; Safi, Malak; Smith, Alexandra; Palui, Goutam; Perez, J Manuel; Mattoussi, Hedi

    2014-06-03

    We have designed a set of multifunctional and multicoordinating polymer ligands that are optimally suited for surface functionalizing iron oxide and potentially other magnetic nanoparticles (NPs) and promoting their integration into biological systems. The amphiphilic polymers are prepared by coupling (via nucleophilic addition) several amine-terminated dopamine anchoring groups, poly(ethylene glycol) moieties, and reactive groups onto a poly(isobutylene-alt-maleic anhydride) (PIMA) chain. This design greatly benefits from the highly efficient and reagent-free one-step reaction of maleic anhydride groups with amine-containing molecules. The availability of several dopamine groups in the same ligand greatly enhances the ligand affinity, via multiple coordination, to the magnetic NPs, while the hydrophilic and reactive groups promote colloidal stability in buffer media and allow subsequent conjugation with target biomolecules. Iron oxide nanoparticles ligand exchanged with these polymer ligands have a compact hydrodynamic size and exhibit enhanced long-term colloidal stability over the pH range of 4-12 and in the presence of excess electrolytes. Nanoparticles ligated with terminally reactive polymers have been easily coupled to target dyes and tested in live cell imaging with no measurable cytotoxicity. Finally, the resulting hydrophilic nanoparticles exhibit large and size-dependent r2 relaxivity values.

  15. Evolution in the design of a low sheath-flow interface for CE-MS and application to biological samples.

    Science.gov (United States)

    González-Ruiz, Víctor; Codesido, Santiago; Rudaz, Serge; Schappler, Julie

    2018-03-01

    Although several interfaces for CE-MS hyphenation are commercially available, the development of new versatile, simple and yet efficient and sensitive alternatives remains an important field of research. In a previous work, a simple low sheath-flow interface was developed from inexpensive parts. This interface features a design easy to build, maintain, and adapt to particular needs. The present work introduces an improved design of the previous interface. By reducing the diameter of the separation capillary and the emitter, a smaller Taylor cone is spontaneously formed, minimizing the zone dispersion while the analytes go through the interface and leading to less peak broadening associated to the ESI process. Numerical modeling allowed studying the mixing and diffusion processes taking place in the Taylor cone. The analytical performance of this new interface was tested with pharmaceutically relevant molecules and endogenous metabolites. The interface was eventually applied to the analysis of neural cell culture samples, allowing the identification of a panel of neurotransmission-related molecules. An excellent migration time repeatability was obtained (intra-day RSD 10 with an injected volume of 6.7 nL of biological extract. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Biological effects of a de novo designed myxoma virus peptide analogue: evaluation of cytotoxicity on tumor cells.

    Directory of Open Access Journals (Sweden)

    Taghrid S Istivan

    Full Text Available BACKGROUND: The Resonant Recognition Model (RRM is a physico-mathematical model that interprets protein sequence linear information using digital signal processing methods. In this study the RRM concept was employed for structure-function analysis of myxoma virus (MV proteins and the design of a short bioactive therapeutic peptide with MV-like antitumor/cytotoxic activity. METHODOLOGY/PRINCIPAL FINDINGS: The analogue RRM-MV was designed by RRM as a linear 18 aa 2.3 kDa peptide. The biological activity of this computationally designed peptide analogue against cancer and normal cell lines was investigated. The cellular cytotoxicity effects were confirmed by confocal immunofluorescence microscopy, by measuring the levels of cytoplasmic lactate dehydrogenase (LDH and by Prestoblue cell viability assay for up to 72 hours in peptide treated and non-treated cell cultures. Our results revealed that RRM-MV induced a significant dose and time-dependent cytotoxic effect on murine and human cancer cell lines. Yet, when normal murine cell lines were similarly treated with RRM-MV, no cytotoxic effects were observed. Furthermore, the non-bioactive RRM designed peptide RRM-C produced negligible cytotoxic effects on these cancer and normal cell lines when used at similar concentrations. The presence/absence of phosphorylated Akt activity in B16F0 mouse melanoma cells was assessed to indicate the possible apoptosis signalling pathway that could be affected by the peptide treatment. So far, Akt activity did not seem to be significantly affected by RRM-MV as is the case for the original viral protein. CONCLUSIONS/SIGNIFICANCE: Our findings indicate the successful application of the RRM concept to design a bioactive peptide analogue (RRM-MV with cytotoxic effects on tumor cells only. This 2.345 kDa peptide analogue to a 49 kDa viral protein may be suitable to be developed as a potential cancer therapeutic. These results also open a new direction to the rational

  17. CHEMICAL EFFECTS IN BIOLOGICAL SYSTEMS – DATA DICTIONARY (CEBS-DD): A COMPENDIUM OF TERMS FOR THE CAPTURE AND INTEGRATION OF BIOLOGICAL STUDY DESIGN DESCRIPTION, CONVENTIONAL PHENOTYPES AND ‘OMICS’ DATA

    Science.gov (United States)

    A critical component in the design of the Chemical Effects in Biological Systems (CEBS) Knowledgebase is a strategy to capture toxicogenomics study protocols and the toxicity endpoint data (clinical pathology and histopathology). A Study is generally an experiment carried out du...

  18. Enabling students to learn: Design, implementation and assessment of a supplemental study strategies course for an introductory undergraduate biology course

    Science.gov (United States)

    Sriram, Jayanthi Sanjeevi

    Attrition in the STEM disciplines is a national problem and one of the important reasons for this is student experiences in introductory courses. A myriad of factors influence students' experiences in those courses; inadequate student preparation is one of the most cited reasons. Incoming freshmen often lack the learning strategies required to meaningfully learn and succeed in college courses. Unfortunately, the instructors have limited time and/or have little experience in teaching learning strategies. In this paper, the design, implementation, and evaluation of a Supplemental Course (SC) model that emphasizes learning strategies is presented. SC was offered concurrently with the introductory biology courses for four consecutive semesters (fall 2011 to spring 2013); for 10 weeks in fall 2012 and 7 weeks in the other semesters at Miami University. 10 weeks SC began earlier in the semester than the shorter SC. This study evaluated the effects of the SC on students' (1) performance in the introductory biology course, (2) perceived changes in self-regulation and social support, and (3) experiences in the introductory biology course before, during, and after participation in the SC. A mixed methods approach was used to address these goals. A pre-post survey was administered to obtain students' use of self-regulation strategies and social-support data. Quantitative methods were utilized to analyze content exam grades and changes in self-regulation strategies and social-support. To explore the experiences of the students, semi-structured interviews were conducted, followed by analysis using grounded theory. The findings reveal that participants of the longer duration SC (with an earlier start date) significantly improved in content exam performance, perceived use of self-regulation strategies, and social support compared to the non-participants. Participants of the shorter duration SC (with a later start date) did not significantly improve in content exam performance

  19. Is synthetic biology mechanical biology?

    Science.gov (United States)

    Holm, Sune

    2015-12-01

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

  20. Ecological Literacy, Urban Green Space, and Mobile Technology: Exploring the Impacts of an Arboretum Curriculum Designed for Undergraduate Biology Courses

    Science.gov (United States)

    Phoebus, Patrick E.

    Increasing individual ecological literacy levels may help citizens make informed choices about the environmental challenges facing society. The purpose of this study was to explore the impacts of an arboretum curriculum incorporating mobile technology and an urban greenspace on the ecological knowledge, environmental attitudes and beliefs, and environmental behaviors of undergraduate biology students and pre-service K-8 teachers during a summer course. Using a convergent parallel mixed-methods design, both quantitative and qualitative data were collected, analyzed, and later merged to create an enhanced understanding of the impact of the curriculum on the environmental attitudes and beliefs of the participants. Quantitative results revealed a significant difference between pre- and post-survey scores for ecological knowledge, with no significant differences between pre- and post-scores for the other variables measured. However, no significant difference in scores was found between experimental and comparison groups for any of the three variables. When the two data sets were compared, results from the quantitative and qualitative components were found to converge and diverge. Quantitative data indicated the environmental attitudes and beliefs of participants were unaffected by the arboretum curriculum. Similarly, qualitative data indicated participants' perceived environmental attitudes and beliefs about the importance of nature remained unchanged throughout the course of the study. However, qualitative data supporting the theme connecting with the curriculum suggested experiences with the arboretum curriculum helped participants develop an appreciation for trees and nature and led them to believe they increased their knowledge about trees.

  1. Paweł Bąk, Die Metapher in der Übersetzung. Studien zum Transfer der Aphorismen von Stanisław Jerzy Lec und der Gedichte von Wisława Szymborska, Peter Lang Europäischer Verlag der Wissenschaft en, Frankfurt am Main u. a. 2007 =...

    OpenAIRE

    Zieliński, Lech

    2008-01-01

    Paweł Bąk, Die Metapher in der Ubersetzung. Studien zum Transfer der Aphorismen von Stanisław Jerzy Lec und der Gedichte von Wisława Szymborska, Peter Lang Europaischer Verlag der Wissenschaft en, Frankfurt am Main u. a. 2007 = Danziger Beitrage zur Germanistik, Bd. 20 wyd. Andrzej Kątny, 332 strony

  2. The concept of biologically motivated time-pulse information processing for design and construction of multifunctional devices of neural logic

    Science.gov (United States)

    Krasilenko, Vladimir G.; Nikolsky, Alexander I.; Lazarev, Alexander A.; Sholohov, V. I.

    2004-04-01

    On the basis of the analysis of advanced approaches and optoelectronic systems for realization of various logics: two-valued, multi-valued, neural, continuous and others the biologically motivated time-pulse conception for building of multifunctional reconfigurable universal elements with programmable tuning for neurobiologic is grounded. The concept consists in usage of preliminary conversion of multi-level or continuous optic 2D signals into durations of time intervals (the conversion to a temporal area) and further use of time-pulse two-level digital signals that allows to ensure fast tuning to a required function of two-valued, multi-valued and other logics. It is shown that optoelectronic pulse-phase and pulse-width modulators (PPM and PWM) are the base elements for that. Time-pulse coding universal elements for matrix two-valued and multi-valued logics and structural-functional design of universal time-pulse coding elements for neural (continuous) logic are considered in the article. PPMs realized on 1.5μm technology CMOS transistors are considered. The PPMs have parameters: the input photocurrent range is 10nA...10μA the conversion period is 10μs...1ms the conversion relative error is 0.1...1%; the conversion law is ramp; the supply voltage is 3V and the power consumption is 83μW. The small power consumption of such PPMs enables successfully their integration in 2Darray with size of 128x128 elements and more and productivity equals 1...10 Giga continuous logic operations per sec.

  3. Design, synthesis and biological activities of new brassinosteroid analogues with a phenyl group in the side chain

    Czech Academy of Sciences Publication Activity Database

    Kvasnica, Miroslav; Oklešťková, Jana; Bazgier, Václav; Rárová, L.; Kořínková, Petra; Mikulík, Jaromír; Buděšínský, Miloš; Béreš, T.; Berka, K.; Lu, Q.; Russinova, E.; Strnad, Miroslav

    2016-01-01

    Roč. 14, č. 37 (2016), s. 8691-8701 ISSN 1477-0520 R&D Projects: GA MŠk(CZ) LO1204; GA ČR GJ15-08202Y; GA MŠk(CZ) LM2015047 Institutional support: RVO:61389030 ; RVO:61388963 Keywords : ASYMMETRIC DIHYDROXYLATION * IMMUNOMODULATORY ACTIVITY * BRI1 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.564, year: 2016

  4. Biology Teachers Designing Context-Based Lessons for Their Classroom Practice--The Importance of Rules-of-Thumb

    Science.gov (United States)

    Wieringa, Nienke; Janssen, Fred J. J. M.; Van Driel, Jan H.

    2011-01-01

    In science education in the Netherlands new, context-based, curricula are being developed. As in any innovation, the outcome will largely depend on the teachers who design and implement lessons. Central to the study presented here is the idea that teachers, when designing lessons, use rules-of-thumb: notions of what a lesson should look like if…

  5. 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.

  6. Design, Synthesis and Biological Activity of Novel Reversible Peptidyl FVIIa Inhibitors Rh-Catalyzed Enantioselective Synthesis of Diaryl Amines

    DEFF Research Database (Denmark)

    Storgaard, Morten

    functional group tolerance. Unfortunately, these -aryl tetramic acids were too unreactive and ring opening toward the synthesis of the building block did not succeed. However, -aryl tetramic acids are still interesting compounds due to their potential biological activity. The building block 3.15 (P1......-catalyzed enantioselective synthesis of diaryl amines, which is an important class of compounds (Chapter 4). For example it is found in the third generation anti-histaminic agent levocetirizine. Development of efficient synthetic routes is therefore of considerably interest. The rhodium-catalyzed enantioselective synthesis...

  7. Designing structural features of novel benznidazole-loaded cationic nanoparticles for inducing slow drug release and improvement of biological efficacy.

    Science.gov (United States)

    Dos Santos-Silva, Alaine M; de Caland, Lilia B; de S L Oliveira, Ana Luíza C; de Araújo-Júnior, Raimundo F; Fernandes-Pedrosa, Matheus F; Cornélio, Alianda Maira; da Silva-Júnior, Arnóbio A

    2017-09-01

    Several polymers have been investigated for producing cationic nanocarriers due to their ability to cross biological barriers. Polycations such as copolymers of polymethylmethacrylate are highlighted due to their biocompatibility and low toxicity. The purpose of this study was to produce small and narrow-sized cationic nanoparticles able to overcome cell membranes and improve the biological activity of benznidazole (BNZ) in normal and cancer cells. The effect of composition and procedure parameters of the used emulsification-solvent evaporation method were controlled for this purpose. The experimental approach included particle size, polydispersity index, zeta potential, atomic force microscopy (AFM), attenuated total reflectance Fourier transforms infrared spectroscopy (ATR- FTIR), drug loading efficiency, and physical stability assays. Spherical and stable (over six weeks) sub 150nm cationic nanoparticles were optimized, with the encapsulation efficiency >80%. The used drug/copolymer ratio modulated the slow drug release, which was adjusted by the parabolic diffusion mathematical model. In addition, the ability of the cationic nanoparticles improve the BNZ uptake in the normal kidney cells (HEK 293) and the human colorectal cancer cells (HT 29) demonstrate that this novel BNZ-loaded cationic has great potential as a chemotherapeutic application of benznidazole. Copyright © 2017. Published by Elsevier B.V.

  8. Design, implementation and practice of JBEI-ICE: an open source biological part registry platform and tools.

    Science.gov (United States)

    Ham, Timothy S; Dmytriv, Zinovii; Plahar, Hector; Chen, Joanna; Hillson, Nathan J; Keasling, Jay D

    2012-10-01

    The Joint BioEnergy Institute Inventory of Composable Elements (JBEI-ICEs) is an open source registry platform for managing information about biological parts. It is capable of recording information about 'legacy' parts, such as plasmids, microbial host strains and Arabidopsis seeds, as well as DNA parts in various assembly standards. ICE is built on the idea of a web of registries and thus provides strong support for distributed interconnected use. The information deposited in an ICE installation instance is accessible both via a web browser and through the web application programming interfaces, which allows automated access to parts via third-party programs. JBEI-ICE includes several useful web browser-based graphical applications for sequence annotation, manipulation and analysis that are also open source. As with open source software, users are encouraged to install, use and customize JBEI-ICE and its components for their particular purposes. As a web application programming interface, ICE provides well-developed parts storage functionality for other synthetic biology software projects. A public instance is available at public-registry.jbei.org, where users can try out features, upload parts or simply use it for their projects. The ICE software suite is available via Google Code, a hosting site for community-driven open source projects.

  9. Efficient biological process characterization by definitive-screening designs: the formaldehyde treatment of a therapeutic protein as a case study.

    Science.gov (United States)

    Erler, Axel; de Mas, Nuria; Ramsey, Philip; Henderson, Grant

    2013-03-01

    As part of the process-characterization campaign of a candidate vaccine product, a recently developed class of three-level designs-definitive-screening designs-was employed to select a quadratic model that describes the effect of six input process parameters, including protein concentration, formaldehyde-to-protein ratio, lysine concentration, reaction duration, pH, and reaction temperature, on a formylation protein-crosslinking reaction. This design requires only 17 experimental runs. The resulting model was then used to simulate 10,000 runs that account for the variability in the inputs expected on manufacturing scale. The extent of protein polymerization was predicted to be within specifications for all simulated runs, demonstrating the robustness of the unit operation for subsequent process validation and future commercial manufacturing.

  10. Review of studies validating the protective efficacy of a new technology designed to compensate adverse biological effects caused by vdu and GSM cell phone radiation

    International Nuclear Information System (INIS)

    Youbicier-Simo, B.J.; Messagier, R.; Fillion-Robin, M

    2001-01-01

    A total of 13 studies were initiated and coordinated by Technolab Research Center in 6 laboratories from 3 countries (France, UK, Japan). These studies were aimed at: 1) investigating potential adverse biological effects associated with exposure to non ionizing radiation emitted by two types of communication devices, video display units and cell phones; 2) assessing the efficacy of a compensation magnetic oscillating technology designed to protect from non ionizing radiation. Five types of biological systems including chicken embryos, young chickens, healthy mice, mice suffering from cancer and humans were used. A set of 10 biological parameters were assessed, including embryonic mortality, hormones, antibodies, haematological parameters, stress, mood, ocular damage, neurogenesis, micronuclei formation and intracellular calcium. Overall endpoints were affected by irradiation, in terms of increased embryonic mortality, immune depression, depletion of hormones crucial for the regulation of the immune system, changes in haematological parameters, increased stress, mood alteration, induction of ophthalmologic disorders, inhibition of the neurogenesis in brain areas associated with memory processes, induction of symptoms of cell dysfunction, apoptosis or cancer, and disruption of trans-membrane fluxes of calcium. On the other hand, the compensation magnetic oscillation technology tested allowed significant correction of altered physiological parameters, as well as improvement or disappearance of observed pathological symptoms (author)

  11. A design of Biological Network in the Basin of Jucar; El diseno de la Red Biologica en la Cuenca del Jucar

    Energy Technology Data Exchange (ETDEWEB)

    Martinez Mas, J F; Correcher Martinez, E; Pinon, A; Martinez Muro, M A; Pujante Mora, A M

    2002-07-01

    In this study results obtained in the design of the Biological Network carried out during the year 2000 in 221 sampling points in 106 rivers of the environment of the Confederation Hidrografica of the Jucar are presented. The Biological network is based in the analysis of hydro morphological physical, chemical and biological parameters (macro invertebrates, diatoms, macrofits and fishes) that allow to know the ecological status of the studied rivers. The quality of the rivers were stablished with BMWP index and completed with the calculation in some selected sampling sites of other indexes: 1CG, macrofits index (IM), diatoms index (ID), ecotrofic index (IE). The results indicate the division of the study area in three big groups: the sampling sites located in the headwaters and small streams, with an excellent conservation state and with the presence of indicative species, the medium upland river sites which are regulated by reservoirs and dams, and the lowland rivers with the biggest accumulation of contamination and the biggest population density. (Author) 13 refs.

  12. Biology Myth-Killers

    Science.gov (United States)

    Lampert, Evan

    2014-01-01

    "Biology Myth-Killers" is an activity designed to identify and correct common misconceptions for high school and college introductory biology courses. Students identify common myths, which double as biology misconceptions, and use appropriate sources to share the "truth" about the myths. This learner-centered activity is a fun…

  13. Participation in a Year-Long CURE Embedded into Major Core Genetics and Cellular and Molecular Biology Laboratory Courses Results in Gains in Foundational Biological Concepts and Experimental Design Skills by Novice Undergraduate Researchers†

    Science.gov (United States)

    Peteroy-Kelly, Marcy A.; Marcello, Matthew R.; Crispo, Erika; Buraei, Zafir; Strahs, Daniel; Isaacson, Marisa; Jaworski, Leslie; Lopatto, David; Zuzga, David

    2017-01-01

    This two-year study describes the assessment of student learning gains arising from participation in a year-long curriculum consisting of a classroom undergraduate research experience (CURE) embedded into second-year, major core Genetics and Cellular and Molecular Biology (CMB) laboratory courses. For the first course in our CURE, students used micro-array or RNAseq analyses to identify genes important for environmental stress responses by Saccharomyces cerevisiae. The students were tasked with creating overexpressing mutants of their genes and designing their own original experiments to investigate the functions of those genes using the overexpression and null mutants in the second CURE course. In order to evaluate student learning gains, we employed three validated concept inventories in a pretest/posttest format and compared gains on the posttest versus the pretest with student laboratory final grades. Our results demonstrated that there was a significant correlation between students earning lower grades in the Genetics laboratory for both years of this study and gains on the Genetics Concept Assessment (GCA). We also demonstrated a correlation between students earning lower grades in the Genetics laboratory and gains on the Introductory Molecular and Cell Biology Assessment (IMCA) for year 1 of the study. Students furthermore demonstrated significant gains in identifying the variable properties of experimental subjects when assessed using the Rubric for Experimental (RED) design tool. Results from the administration of the CURE survey support these findings. Our results suggest that a year-long CURE enables lower performing students to experience greater gains in their foundational skills for success in the STEM disciplines. PMID:28904646

  14. Design, synthesis, molecular docking and biological evaluation of new dithiocarbamates substituted benzimidazole and chalcones as possible chemotherapeutic agents.

    Science.gov (United States)

    Bacharaju, Keerthana; Jambula, Swathi Reddy; Sivan, Sreekanth; Jyostnatangeda, Saritha; Manga, Vijjulatha

    2012-05-01

    A series of novel dithiocarbamates with benzimidazole and chalcone scaffold have been designed synthesised and evaluated for their antimitotic activity. Compounds 4c and 9d display the most promising antimitotic activity with IC(50) of 1.66 μM and 1.52 μM respectively. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Design, synthesis and biological evaluation of tacrine-1,2,3-triazole derivatives as potent cholinesterase inhibitors

    DEFF Research Database (Denmark)

    Wu, Gaochan; Gao, Yun; Kang, Dongwei

    2018-01-01

    acetylcholinesterase (AChE) and horse serum butyrylcholinesterase (BChE) as potential drug targets for Alzheimer's disease (AD). Among the designed compounds, compound 8a2 exhibited potent inhibition against AChE and BChE with IC50 values of 4.89 μM and 3.61 μM, respectively. Further structure-activity relationship...

  16. Teaching Evolution at A-Level: Is "Intelligent Design" a Scientific Theory That Merits Inclusion in the Biology Syllabus?

    Science.gov (United States)

    Freeland, Peter

    2013-01-01

    Charles Darwin supposed that evolution involved a process of gradual change, generated randomly, with the selection and retention over many generations of survival-promoting features. Some theists have never accepted this idea. "Intelligent design" is a relatively recent theory, supposedly based on scientific evidence, which attempts to…

  17. Control structure design for resource recovery using the enhanced biological phosphorus removal and recovery (EBP2R) activated sludge process

    DEFF Research Database (Denmark)

    Valverde Perez, Borja; Fuentes-Martínez, José Manuel; Flores Alsina, Xavier

    2016-01-01

    , it is concluded that the SBR is the most effective reactor configuration for the EBP2R process. Importantly, the designed control structures rely on control loops that do not require chemical dosing for nutrient management, thereby reducing the environmental footprint of the EBP2R process. The proposed control...

  18. Dynamic lighting for well-being in work places: Addressing the visual, emotional and biological aspects of lighting design.

    NARCIS (Netherlands)

    Knoop, M.

    2006-01-01

    Light can be used to increase alertness, evoke relaxation and suppress sleepiness. Therefore, it can be deployed to support the well-being and performance of people in working places. These socalled ‘non-visual’ or ‘biological’ effects have become an increasingly important topic in lighting design

  19. Dynamic lighting for well-being in work places: Addressing the visual, emotional and biological aspects of lighting design

    NARCIS (Netherlands)

    Knoop, M.

    2006-01-01

    Light can be used to increase alertness, evoke relaxation and suppress sleepiness. Therefore, it can be deployed to support the well-being and performance of people in working places. These socalled ‘non-visual’ or ‘biological’ effects have become an increasingly important topic in lighting design

  20. Design and implementation of optical imaging and sensor systems for characterization of deep-sea biological camouflage

    Science.gov (United States)

    Haag, Justin Mathew

    The visual ecology of deep-sea animals has long been of scientific interest. In the open ocean, where there is no physical structure to hide within or behind, diverse strategies have evolved to solve the problem of camouflage from a potential predator. Simulations of specific predator-prey scenarios have yielded estimates of the range of possible appearances that an animal may exhibit. However, there is a limited amount of quantitative information available related to both animal appearance and the light field at mesopelagic depths (200 m to 1000 m). To mitigate this problem, novel optical instrumentation, taking advantage of recent technological advances, was developed and is described in this dissertation. In the first half of this dissertation, the appearance of mirrored marine animals is quantitatively evaluated. A portable optical imaging scatterometer was developed to measure angular reflectance, described by the bidirectional reflectance distribution function (BRDF), of biological specimens. The instrument allows for BRDF capture from samples of arbitrary size, over a significant fraction of the reflectance hemisphere. Multiple specimens representing two species of marine animals, collected at mesopelagic depths, were characterized using the scatterometer. Low-dimensional parametric models were developed to simplify use of the data sets, and to validate the BRDF method. Results from principal component analysis confirm that BRDF measurements can be used to study intra- and interspecific variability of mirrored marine animal appearance. Collaborative efforts utilizing the BRDF data sets to develop physically-based scattering models are underway. In the second half of this dissertation, another key part of the deep-sea biological camouflage problem is examined. Two underwater radiometers, capable of low-light measurements, were developed to address the lack of available information related to the deep-sea light field. Quantitative comparison of spectral

  1. Design

    DEFF Research Database (Denmark)

    Volf, Mette

    This publication is unique in its demystification and operationalization of the complex and elusive nature of the design process. The publication portrays the designer’s daily work and the creative process, which the designer is a part of. Apart from displaying the designer’s work methods...... and design parameters, the publication shows examples from renowned Danish design firms. Through these examples the reader gets an insight into the designer’s reality....

  2. Design, synthesis, and in vitro transfection biology of novel tocopherol based monocationic lipids: a structure-activity investigation.

    Science.gov (United States)

    Kedika, Bhavani; Patri, Srilakshmi V

    2011-01-27

    Herein, we report on the design, synthesis, and in vitro gene delivery efficacies of five novel tocopherol based cationic lipids (1-5) in transfecting CHO, B16F10, A-549, and HepG2 cells. The in vitro gene transfer efficiencies of lipids (1-5) were evaluated by both β-galactosidase reporter gene expression and inverted fluorescent microscopic experiments. The results of the present structure-activity investigation convincingly demonstrate that the tocopherol based lipid with three hydroxyl groups in its headgroup region showed 4-fold better transfection efficiency than the commercial formulation. The results also demonstrate that these tocopherol based lipids may be targeted to liver. Transfection efficiency of all the relevant lipids was maintained even when the serum was present during the transfection conditions. The results indicated that the designed systems are quite capable of transferring the DNA into all four types of cells studied with low or no toxicity.

  3. Designing and conducting tabletop exercises to assess public health preparedness for manmade and naturally occurring biological threats

    Directory of Open Access Journals (Sweden)

    Dausey David J

    2007-05-01

    Full Text Available Abstract Background Since 2001, state and local health departments in the United States (US have accelerated efforts to prepare for high-impact public health emergencies. One component of these activities has been the development and conduct of exercise programs to assess capabilities, train staff and build relationships. This paper summarizes lessons learned from tabletop exercises about public health emergency preparedness and about the process of developing, conducting, and evaluating them. Methods We developed, conducted, and evaluated 31 tabletop exercises in partnership with state and local health departments throughout the US from 2003 to 2006. Participant self evaluations, after action reports, and tabletop exercise evaluation forms were used to identify aspects of the exercises themselves, as well as public health emergency responses that participants found more or less challenging, and to highlight lessons learned about tabletop exercise design. Results Designing the exercises involved substantial collaboration with representatives from participating health departments to assure that the scenarios were credible, focused attention on local preparedness needs and priorities, and were logistically feasible to implement. During execution of the exercises, nearly all health departments struggled with a common set of challenges relating to disease surveillance, epidemiologic investigations, communications, command and control, and health care surge capacity. In contrast, performance strengths were more varied across participating sites, reflecting specific attributes of individual health departments or communities, experience with actual public health emergencies, or the emphasis of prior preparedness efforts. Conclusion The design, conduct, and evaluation of the tabletop exercises described in this report benefited from collaborative planning that involved stakeholders from participating health departments and exercise developers and

  4. Why we should use simpler models if the data allow this: relevance for ANOVA designs in experimental biology

    Directory of Open Access Journals (Sweden)

    Lazic Stanley E

    2008-07-01

    Full Text Available Abstract Background Analysis of variance (ANOVA is a common statistical technique in physiological research, and often one or more of the independent/predictor variables such as dose, time, or age, can be treated as a continuous, rather than a categorical variable during analysis – even if subjects were randomly assigned to treatment groups. While this is not common, there are a number of advantages of such an approach, including greater statistical power due to increased precision, a simpler and more informative interpretation of the results, greater parsimony, and transformation of the predictor variable is possible. Results An example is given from an experiment where rats were randomly assigned to receive either 0, 60, 180, or 240 mg/L of fluoxetine in their drinking water, with performance on the forced swim test as the outcome measure. Dose was treated as either a categorical or continuous variable during analysis, with the latter analysis leading to a more powerful test (p = 0.021 vs. p = 0.159. This will be true in general, and the reasons for this are discussed. Conclusion There are many advantages to treating variables as continuous numeric variables if the data allow this, and this should be employed more often in experimental biology. Failure to use the optimal analysis runs the risk of missing significant effects or relationships.

  5. Five Years of Designing Wireless Sensor Networks in the Doñana Biological Reserve (Spain): An Applications Approach

    Science.gov (United States)

    Larios, Diego F.; Barbancho, Julio; Sevillano, José L.; Rodríguez, Gustavo; Molina, Francisco J.; Gasull, Virginia G.; Mora-Merchan, Javier M.; León, Carlos

    2013-01-01

    Wireless Sensor Networks (WSNs) are a technology that is becoming very popular for many applications, and environmental monitoring is one of its most important application areas. This technology solves the lack of flexibility of wired sensor installations and, at the same time, reduces the deployment costs. To demonstrate the advantages of WSN technology, for the last five years we have been deploying some prototypes in the Doñana Biological Reserve, which is an important protected area in Southern Spain. These prototypes not only evaluate the technology, but also solve some of the monitoring problems that have been raised by biologists working in Doñana. This paper presents a review of the work that has been developed during these five years. Here, we demonstrate the enormous potential of using machine learning in wireless sensor networks for environmental and animal monitoring because this approach increases the amount of useful information and reduces the effort that is required by biologists in an environmental monitoring task. PMID:24025554

  6. Five years of designing wireless sensor networks in the Doñana Biological Reserve (Spain): an applications approach.

    Science.gov (United States)

    Larios, Diego F; Barbancho, Julio; Sevillano, José L; Rodríguez, Gustavo; Molina, Francisco J; Gasull, Virginia G; Mora-Merchan, Javier M; León, Carlos

    2013-09-10

    Wireless Sensor Networks (WSNs) are a technology that is becoming very popular for many applications, and environmental monitoring is one of its most important application areas. This technology solves the lack of flexibility of wired sensor installations and, at the same time, reduces the deployment costs. To demonstrate the advantages of WSN technology, for the last five years we have been deploying some prototypes in the Doñana Biological Reserve, which is an important protected area in Southern Spain. These prototypes not only evaluate the technology, but also solve some of the monitoring problems that have been raised by biologists working in Doñana. This paper presents a review of the work that has been developed during these five years. Here, we demonstrate the enormous potential of using machine learning in wireless sensor networks for environmental and animal monitoring because this approach increases the amount of useful information and reduces the effort that is required by biologists in an environmental monitoring task.

  7. Feedstock Supply System Design and Economics for Conversion of Lignocellulosic Biomass to Hydrocarbon Fuels: Conversion Pathway: Biological Conversion of Sugars to Hydrocarbons The 2017 Design Case

    Energy Technology Data Exchange (ETDEWEB)

    Kevin Kenney; Kara G. Cafferty; Jacob J. Jacobson; Ian J Bonner; Garold L. Gresham; William A. Smith; David N. Thompson; Vicki S. Thompson; Jaya Shankar Tumuluru; Neal Yancey

    2013-09-01

    The U.S. Department of Energy promotes the production of a range of liquid fuels and fuel blendstocks from lignocellulosic biomass feedstocks by funding fundamental and applied research that advances the state of technology in biomass collection, conversion, and sustainability. As part of its involvement in this program, the Idaho National Laboratory (INL) investigates the feedstock logistics economics and sustainability of these fuels. Between 2000 and 2012, INL conducted a campaign to quantify the economics and sustainability of moving biomass from standing in the field or stand to the throat of the biomass conversion process. The goal of this program was to establish the current costs based on conventional equipment and processes, design improvements to the current system, and to mark annual improvements based on higher efficiencies or better designs. The 2012 programmatic target was to demonstrate a delivered biomass logistics cost of $35/dry ton. This goal was successfully achieved in 2012 by implementing field and process demonstration unit-scale data from harvest, collection, storage, preprocessing, handling, and transportation operations into INL’s biomass logistics model. Looking forward to 2017, the programmatic target is to supply biomass to the conversion facilities at a total cost of $80/dry ton and on specification with in-feed requirements. The goal of the 2017 Design Case is to enable expansion of biofuels production beyond highly productive resource areas by breaking the reliance of cost-competitive biofuel production on a single, abundant, low-cost feedstock. If this goal is not achieved, biofuel plants are destined to be small and/or clustered in select regions of the country that have a lock on low-cost feedstock. To put the 2017 cost target into perspective of past accomplishments of the cellulosic ethanol pathway, the $80 target encompasses total delivered feedstock cost, including both grower payment and logistics costs, while meeting all

  8. Rational design, synthesis, biologic evaluation, and structure-activity relationship studies of novel 1-indanone alpha(1)-adrenoceptor antagonists.

    Science.gov (United States)

    Li, Minyong; Xia, Lin

    2007-11-01

    In the present report, a novel series of 1-indanone alpha(1)-adrenoceptor antagonists were designed and synthesized based on 3D-pharmacophore model. Their in vitro alpha(1)-adrenoceptor antagonistic assay showed that three compounds (2a, 2m, and 2o) had similar or improved alpha(1)-adrenoceptor antagonistic activities relative to the positive control prazosin. Based on these results, a three-dimensional quantitative structure-activity relationship study was performed using a Self-Organizing Molecular Field Analysis method to provide insight for the future development of alpha(1)-adrenoceptor antagonists.

  9. Design, Synthesis and Biological Evaluation of 1,4-Disubstituted-3,4-dihydroisoquinoline Compounds as New Tubulin Polymerization Inhibitors

    Directory of Open Access Journals (Sweden)

    Ling Zhang

    2015-05-01

    Full Text Available A series of 1,4-disubstituted-3,4-dihydroisoquinoline derivatives designed as tubulin polymerization inhibitors were synthesized. Their cytotoxic activities against the CEM leukemia cell line were evaluated. Most of them displayed moderate cytotoxic activities, and compounds 21 and 32 showed good activities with IC50 of 4.10 and 0.64 μM, respectively. The most potent compound 32 was further confirmed to be able to inhibit tubulin polymerization, and its hypothetical binding mode with tubulin was obtained by molecular docking.

  10. Design, synthesis, molecular modeling and biological evaluation of novel diaryl heterocyclic analogs as potential selective cyclooxygenase-2 (COX-2 inhibitors

    Directory of Open Access Journals (Sweden)

    Deema A. Al-Turki

    2017-01-01

    Full Text Available New series of 3,4-diaryl-2-thioxoimidazolidin-4-ones and 3-alkylthio-4,5-diaryl-4H-1,2,4-triazoles were designed, synthesized and evaluated for their activity as anti-inflammatory agents. Compounds 20, 21, 23 and 34 are highly selective inhibitors of COX-2 enzyme at a concentration of 100 mM relative to celecoxib, the standard reference. (±-3-(4-Phenoxy-phenyl-5-phenyl-2-thioxoimidazolidin-4-ones 23 exhibited the most active anti-inflammatory agent.

  11. Design, synthesis and biological activity of 6-substituted carbamoyl benzimidazoles as new nonpeptidic angiotensin II AT₁ receptor antagonists.

    Science.gov (United States)

    Zhang, Jun; Wang, Jin-Liang; Zhou, Zhi-Ming; Li, Zhi-Huai; Xue, Wei-Zhe; Xu, Di; Hao, Li-Ping; Han, Xiao-Feng; Fei, Fan; Liu, Ting; Liang, Ai-Hua

    2012-07-15

    A series of 6-substituted carbamoyl benzimidazoles were designed and synthesised as new nonpeptidic angiotensin II AT(1) receptor antagonists. The preliminary pharmacological evaluation revealed a nanomolar AT(1) receptor binding affinity for all compounds in the series, and a potent antagonistic activity in an isolated rabbit aortic strip functional assay for compounds 6f, 6g, 6h and 6k was also demonstrated. Furthermore, evaluation in spontaneous hypertensive rats and a preliminary toxicity evaluation showed that compound 6g is an orally active AT(1) receptor antagonist with low toxicity. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Structure-Based Design, Synthesis, Biological Evaluation, and Molecular Docking of Novel PDE10 Inhibitors with Antioxidant Activities

    Science.gov (United States)

    Li, Jinxuan; Chen, Jing-Yi; Deng, Ya-Lin; Zhou, Qian; Wu, Yinuo; Wu, Deyan; Luo, Hai-Bin

    2018-05-01

    Phosphodiesterase 10 is a promising target for the treatment of a series of central nervous system (CNS) diseases. Imbalance between oxidative stress and antioxidant defense systems as a universal condition in neurodegenerative disorders is widely studied as a potential therapy for CNS diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). To discover multifunctional pharmaceuticals as a treatment for neurodegenerative diseases, a series of quinazoline-based derivatives with PDE10 inhibitory activities and antioxidant activities were designed and synthesized. Nine out of thirteen designed compounds showed good PDE10 inhibition at the concentration of 1.0 μM. Among these compounds, eight exhibited moderate to excellent antioxidant activity with ORAC (oxygen radical absorbance capacity) value above 1.0. Molecular docking was performed for better understanding of the binding patterns of these compounds with PDE10. Compound 11e, which showed remarkable inhibitory activity against PDE10 and antioxidant activity may serve as a lead for the further modification.

  13. New 5-benzylidenethiazolidin-4-one inhibitors of bacterial MurD ligase: design, synthesis, crystal structures, and biological evaluation.

    Science.gov (United States)

    Zidar, Nace; Tomašić, Tihomir; Šink, Roman; Kovač, Andreja; Patin, Delphine; Blanot, Didier; Contreras-Martel, Carlos; Dessen, Andréa; Premru, Manica Müller; Zega, Anamarija; Gobec, Stanislav; Mašič, Lucija Peterlin; Kikelj, Danijel

    2011-11-01

    Mur ligases (MurC-MurF), a group of bacterial enzymes that catalyze four consecutive steps in the formation of cytoplasmic peptidoglycan precursor, are becoming increasingly adopted as targets in antibacterial drug design. Based on the crystal structure of MurD cocrystallized with thiazolidine-2,4-dione inhibitor I, we have designed, synthesized, and evaluated a series of improved glutamic acid containing 5-benzylidenerhodanine and 5-benzylidenethiazolidine-2,4-dione inhibitors of MurD with IC(50) values up to 28 μM. Inhibitor 37, with an IC(50) of 34 μM, displays a weak antibacterial activity against S. aureus ATCC 29213 and E. faecalis ATCC 29212 with minimal inhibitory concentrations of 128 μg/mL. High-resolution crystal structures of MurD in complex with two new inhibitors (compounds 23 and 51) reveal details of their binding modes within the active site and provide valuable information for further structure-based optimization. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  14. In silico design and biological evaluation of a dual specificity kinase inhibitor targeting cell cycle progression and angiogenesis.

    Directory of Open Access Journals (Sweden)

    Antony M Latham

    Full Text Available Protein kinases play a central role in tumor progression, regulating fundamental processes such as angiogenesis, proliferation and metastasis. Such enzymes are an increasingly important class of drug target with small molecule kinase inhibitors being a major focus in drug development. However, balancing drug specificity and efficacy is problematic with off-target effects and toxicity issues.We have utilized a rational in silico-based approach to demonstrate the design and study of a novel compound that acts as a dual inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2 and cyclin-dependent kinase 1 (CDK1. This compound acts by simultaneously inhibiting pro-angiogenic signal transduction and cell cycle progression in primary endothelial cells. JK-31 displays potent in vitro activity against recombinant VEGFR2 and CDK1/cyclin B proteins comparable to previously characterized inhibitors. Dual inhibition of the vascular endothelial growth factor A (VEGF-A-mediated signaling response and CDK1-mediated mitotic entry elicits anti-angiogenic activity both in an endothelial-fibroblast co-culture model and a murine ex vivo model of angiogenesis.We deduce that JK-31 reduces the growth of both human endothelial cells and human breast cancer cells in vitro. This novel synthetic molecule has broad implications for development of similar multi-kinase inhibitors with anti-angiogenic and anti-cancer properties. In silico design is an attractive and innovative method to aid such drug discovery.

  15. In silico design and biological evaluation of a dual specificity kinase inhibitor targeting cell cycle progression and angiogenesis.

    Science.gov (United States)

    Latham, Antony M; Kankanala, Jayakanth; Fearnley, Gareth W; Gage, Matthew C; Kearney, Mark T; Homer-Vanniasinkam, Shervanthi; Wheatcroft, Stephen B; Fishwick, Colin W G; Ponnambalam, Sreenivasan

    2014-01-01

    Protein kinases play a central role in tumor progression, regulating fundamental processes such as angiogenesis, proliferation and metastasis. Such enzymes are an increasingly important class of drug target with small molecule kinase inhibitors being a major focus in drug development. However, balancing drug specificity and efficacy is problematic with off-target effects and toxicity issues. We have utilized a rational in silico-based approach to demonstrate the design and study of a novel compound that acts as a dual inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2) and cyclin-dependent kinase 1 (CDK1). This compound acts by simultaneously inhibiting pro-angiogenic signal transduction and cell cycle progression in primary endothelial cells. JK-31 displays potent in vitro activity against recombinant VEGFR2 and CDK1/cyclin B proteins comparable to previously characterized inhibitors. Dual inhibition of the vascular endothelial growth factor A (VEGF-A)-mediated signaling response and CDK1-mediated mitotic entry elicits anti-angiogenic activity both in an endothelial-fibroblast co-culture model and a murine ex vivo model of angiogenesis. We deduce that JK-31 reduces the growth of both human endothelial cells and human breast cancer cells in vitro. This novel synthetic molecule has broad implications for development of similar multi-kinase inhibitors with anti-angiogenic and anti-cancer properties. In silico design is an attractive and innovative method to aid such drug discovery.

  16. Design, synthesis, and biological evaluation of resveratrol analogues as aromatase and quinone reductase 2 inhibitors for chemoprevention of cancer

    International Nuclear Information System (INIS)

    Sun, Bin; Hoshino, Juma; Jermihov, Katie; Marler, Laura; Pezzuto, John M.; Mesecar, Andrew D.; Cushman, Mark

    2010-01-01

    A series of new resveratrol analogues were designed and synthesized and their inhibitory activities against aromatase were evaluated. The crystal structure of human aromatase (PDB 3eqm) was used to rationalize the mechanism of action of the aromatase inhibitor 32 (IC 50 0.59 μM) through docking, molecular mechanics energy minimization, and computer graphics molecular modeling, and the information was utilized to design several very potent inhibitors, including compounds 82 (IC 50 70 nM) and 84 (IC 50 36 nM). The aromatase inhibitory activities of these compounds are much more potent than that for the lead compound resveratrol, which has an IC 50 of 80 μM. In addition to aromatase inhibitory activity, compounds 32 and 44 also displayed potent QR2 inhibitory activity (IC 50 1.7 μM and 0.27 μM, respectively) and the high-resolution X-ray structures of QR2 in complex with these two compounds provide insight into their mechanism of QR2 inhibition. The aromatase and quinone reductase inhibitors resulting from these studies have potential value in the treatment and prevention of cancer.

  17. Design and development of electrochemical polymer-based lab-on-a-disc devices for biological applications

    DEFF Research Database (Denmark)

    Sanger, Kuldeep

    of pHCA. The second generation LoD device (with integrated SLM extraction) was more advanced and facilitated extraction, enrichment, as well as electrochemical detection of pHCA from the complex sample matrix, i.e., E. coli supernatant at different time points during the cell culture. Realizing......The need for reliable, fast, easy to use, portable and cost effective analytical tools has led to several novel approaches in the development of miniaturized microfluidic platforms integrated with electrochemical sensors. This thesis presents the design and development of an electrochemical...... filtration) was used to quantify pHCA at the end of bacterial culture (24 hours) when the cell density is the highest. We demonstrated the efficiency of the centrifugal filtration, which enabled cell-free electrochemical detection eliminating the effect of high cell density on electrochemical quantification...

  18. Design, Synthesis and Biological Evaluation of Novel Bromophenol Derivatives Incorporating Indolin-2-One Moiety as Potential Anticancer Agents

    Directory of Open Access Journals (Sweden)

    Li-Jun Wang

    2015-02-01

    Full Text Available A series of bromophenol derivatives containing indolin-2-one moiety were designed and evaluated that for their anticancer activities against A549, Bel7402, HepG2, HeLa and HCT116 cancer cell lines using MTT assay in vitro. Among them, seven compounds (4g–4i, 5h, 6d, 7a, 7b showed potent activity against the tested five human cancer cell lines. Wound-healing assay demonstrated that compound 4g can be used as a potent compound for inactivating invasion and metastasis by inhibiting the migration of cancer cells. The structure–activity relationships (SARs of bromophenol derivatives had been discussed, which were useful for exploring and developing bromophenol derivatives as novel anticancer drugs.

  19. Design, synthesis and biological evaluation of 5-fluorouracil-derived benzimidazoles as novel type of potential antimicrobial agents.

    Science.gov (United States)

    Fang, Xue-Jie; Jeyakkumar, Ponmani; Avula, Srinivasa Rao; Zhou, Qian; Zhou, Cheng-He

    2016-06-01

    A series of 5-fluorouracil benzimidazoles as novel type of potential antimicrobial agents were designed and synthesized for the first time. Bioactive assay manifested that some of the prepared compounds exhibited good or even stronger antibacterial and antifungal activities against the tested strains in comparison with reference drugs norfloxacin, chloromycin and fluconazole. Noticeably, 3-fluorobenzyl benzimidazole derivative 5c gave remarkable antimicrobial activities against Saccharomyces cerevisiae, MRSA and Bacillus proteus with MIC values of 1, 2 and 4μg/mL, respectively. Experimental research revealed that compound 5c could effectively intercalate into calf thymus DNA to form compound 5c-DNA complex which might block DNA replication and thus exert antimicrobial activities. Molecular docking indicated that compound 5c should bind with DNA topoisomerase IA through three hydrogen bonds by the use of fluorine atom and oxygen atoms in 5-fluorouracil with the residue Lys 423. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Rational design, synthesis and biological screening of triazine-triazolopyrimidine hybrids as multitarget anti-Alzheimer agents.

    Science.gov (United States)

    Jameel, Ehtesham; Meena, Poonam; Maqbool, Mudasir; Kumar, Jitendra; Ahmed, Waqar; Mumtazuddin, Syed; Tiwari, Manisha; Hoda, Nasimul; Jayaram, B

    2017-08-18

    In our endeavor towards the development of potent multitarget ligands for the treatment of Alzheimer's disease, a series of triazine-triazolopyrimidine hybrids were designed, synthesized and characterized by various spectral techniques. Docking and scoring techniques were used to design the inhibitors and to display their interaction with key residues of active site. Organic synthesis relied upon convergent synthetic routes were mono and di-substituted triazines were connected with triazolopyrimidine using piperazine as a linker. In total, seventeen compounds were synthesized in which the di-substituted triazine-triazolopyrimidine derivatives 9a-d showed better acetylcholinesterase (AChE) inhibitory activity than the corresponding tri-substituted triazine-triazolopyrimidine derivatives 10a-f. Out of the disubstituted triazine-triazolopyrimidine based compounds, 9a and 9b showed encouraging inhibitory activity on AChE with IC 50 values 0.065 and 0.092 μM, respectively. Interestingly, 9a and 9b also demonstrated good inhibition selectivity towards AChE over BuChE by ∼28 folds. Furthermore, kinetic analysis and molecular modeling studies showed that 9a and 9b target both catalytic active site as well as peripheral anionic site of AChE. In addition, these derivatives effectively modulated Aβ self-aggregation as investigated through CD spectroscopy, ThT fluorescence assay and electron microscopy. Besides, these compounds exhibited potential antioxidants (2.15 and 2.91 trolox equivalent by ORAC assay) and metal chelating properties. In silico ADMET profiling highlighted that, these novel triazine derivatives have appropriate drug like properties and possess very low toxic effects in the primarily pharmacokinetic study. Overall, the multitarget profile exerted by these novel triazine molecules qualified them as potential anti-Alzheimer drug candidates in AD therapy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  1. Design, synthesis and biological evaluation of LBM-A5 derivatives as potent P-glycoprotein-mediated multidrug resistance inhibitors.

    Science.gov (United States)

    Wu, Yuxiang; Pan, Miaobo; Dai, Yuxuan; Liu, Baomin; Cui, Jian; Shi, Wei; Qiu, Qianqian; Huang, Wenlong; Qian, Hai

    2016-05-15

    A novel series of P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) inhibitors with triazol-N-phenethyl-tetrahydroisoquinoline or triazol-N-ethyl-tetrahydroisoquinoline scaffold were designed and synthesized via click chemistry. Most of the synthesized compounds showed higher reversal activity than verapamil (VRP). Among them, the most potent compound 4 showed a comparable activity with the known potent P-gp inhibitor WK-X-34 with lower cytotoxicity toward K562 cells (IC50>100μM). Compared with VRP, compound 4 exhibited more potency in increasing drug accumulation in K562/A02 MDR cells. Moreover, compound 4 could significantly reverse MDR in a dose-dependent manner and also persist longer chemo-sensitizing effect than VRP with reversibility. Further mechanism studies revealed that compound 4 could remarkably increase the intracellular accumulation of Adriamycin (ADM) in K562/A02 cells as well as inhibit rhodamine-123 (Rh123) efflux from the cells. These results suggested that compound 4 may represent a promising candidate for developing P-gp-mediated MDR inhibitors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Novel Bifunctional Quinolonyl Diketo Acid Derivatives as HIV-1 Integrase Inhibitors: Design, Synthesis, Biological Activities and Mechanism of Action

    Science.gov (United States)

    Di Santo, Roberto; Costi, Roberta; Roux, Alessandra; Artico, Marino; Lavecchia, Antonio; Marinelli, Luciana; Novellino, Ettore; Palmisano, Lucia; Andreotti, Mauro; Amici, Roberta; Galluzzo, Clementina Maria; Nencioni, Lucia; Palamara, Anna Teresa; Pommier, Yves; Marchand, Christophe

    2008-01-01

    The virally encoded integrase protein is an essential enzyme in the life cycle of the HIV-1 virus and represents an attractive and validated target in the development of therapeutics against HIV infection. Drugs that selectively inhibit this enzyme, when used in combination with inhibitors of reverse transcriptase and protease, are believed to be highly effective in suppressing the viral replication. Among the HIV-1 integrase inhibitors, the β-diketo acids (DKAs) represent a major lead for anti-HIV-1drug development. In this study, novel bifunctional quinolonyl diketo acid derivatives were designed, synthesized and tested for their inhibitory ability against HIV-1 integrase. The compounds are potent inhibitors of integrase activity. Particularly, derivative 8 is a potent IN inhibitor for both steps of the reaction (3′-processing and strand transfer) and exhibits both high antiviral activity against HIV-1 infected cells and low cytotoxicity. Molecular modeling studies provide a plausible mechanism of action, which is consistent with ligand SARs and enzyme photo-crosslinking experiments. PMID:16539381

  3. Design, synthesis, biological assessment and molecular docking studies of new 2-aminoimidazole-quinoxaline hybrids as potential anticancer agents

    Science.gov (United States)

    Ghanbarimasir, Zahra; Bekhradnia, Ahmadreza; Morteza-Semnani, Katayoun; Rafiei, Alireza; Razzaghi-Asl, Nima; Kardan, Mostafa

    2018-04-01

    In a search for novel antiproliferative agents, a series of quinoxaline derivatives containing 2-aminoimidazole (8a-8x) were designed and synthesized. The structures of synthesized compounds were confirmed by IR, 1H NMR, 13C NMR, Mass Spectroscopy and analyzed using HSQC, COSY, ROESY, HMBC techniques. The anticancer activity of all derivatives were evaluated for colon cancer and breast cancer cell lines by the MTT assay and acridine orange/ethidium bromide double staining method. The anti-cancer effect in human colon cancer (HCT-116) and breast cancer (MCF-7) cell lines exhibited that compounds 8a, 8s, 8t, 8w, 8x appeared as potent antiproliferative agents and especially inhibited the human colon cancer cell proliferation with percentage of inhibition by over 50%. The most active compound was (E)-4-phenyl-1-((quinoxalin-2-ylmethylene)amino)-1H-imidazol-2-amine (8a) with the highest inhibition for MCF-7 (83.3%) and HCT-116 (70%) cell lines after 48 and 24 h, respectively. Molecular docking studies of these derivatives within c-kit active site as a validated target might be suggested them as appropriate candidates for further efforts toward more potent anticancer compounds.

  4. An overview of the challenges in designing, integrating, and delivering BARD: a public chemical biology resource and query portal across multiple organizations, locations, and disciplines

    Science.gov (United States)

    de Souza, Andrea; Bittker, Joshua; Lahr, David; Brudz, Steve; Chatwin, Simon; Oprea, Tudor I.; Waller, Anna; Yang, Jeremy; Southall, Noel; Guha, Rajarshi; Schurer, Stephan; Vempati, Uma; Southern, Mark R.; Dawson, Eric S.; Clemons, Paul A.; Chung, Thomas D.Y.

    2015-01-01

    Recent industry-academic partnerships involve collaboration across disciplines, locations, and organizations using publicly funded “open-access” and proprietary commercial data sources. These require effective integration of chemical and biological information from diverse data sources, presenting key informatics, personnel, and organizational challenges. BARD (BioAssay Research Database) was conceived to address these challenges and to serve as a community-wide resource and intuitive web portal for public-sector chemical biology data. Its initial focus is to enable scientists to more effectively use the NIH Roadmap Molecular Libraries Program (MLP) data generated from 3-year pilot and 6-year production phases of the Molecular Libraries Probe Production Centers Network (MLPCN), currently in its final year. BARD evolves the current data standards through structured assay and result annotations that leverage the BioAssay Ontology (BAO) and other industry-standard ontologies, and a core hierarchy of assay definition terms and data standards defined specifically for small-molecule assay data. We have initially focused on migrating the highest-value MLP data into BARD and bringing it up to this new standard. We review the technical and organizational challenges overcome by the inter-disciplinary BARD team, veterans of public and private sector data-integration projects, collaborating to describe (functional specifications), design (technical specifications), and implement this next-generation software solution. PMID:24441647

  5. An Overview of the Challenges in Designing, Integrating, and Delivering BARD: A Public Chemical-Biology Resource and Query Portal for Multiple Organizations, Locations, and Disciplines.

    Science.gov (United States)

    de Souza, Andrea; Bittker, Joshua A; Lahr, David L; Brudz, Steve; Chatwin, Simon; Oprea, Tudor I; Waller, Anna; Yang, Jeremy J; Southall, Noel; Guha, Rajarshi; Schürer, Stephan C; Vempati, Uma D; Southern, Mark R; Dawson, Eric S; Clemons, Paul A; Chung, Thomas D Y

    2014-06-01

    Recent industry-academic partnerships involve collaboration among disciplines, locations, and organizations using publicly funded "open-access" and proprietary commercial data sources. These require the effective integration of chemical and biological information from diverse data sources, which presents key informatics, personnel, and organizational challenges. The BioAssay Research Database (BARD) was conceived to address these challenges and serve as a community-wide resource and intuitive web portal for public-sector chemical-biology data. Its initial focus is to enable scientists to more effectively use the National Institutes of Health Roadmap Molecular Libraries Program (MLP) data generated from the 3-year pilot and 6-year production phases of the Molecular Libraries Probe Production Centers Network (MLPCN), which is currently in its final year. BARD evolves the current data standards through structured assay and result annotations that leverage BioAssay Ontology and other industry-standard ontologies, and a core hierarchy of assay definition terms and data standards defined specifically for small-molecule assay data. We initially focused on migrating the highest-value MLP data into BARD and bringing it up to this new standard. We review the technical and organizational challenges overcome by the interdisciplinary BARD team, veterans of public- and private-sector data-integration projects, who are collaborating to describe (functional specifications), design (technical specifications), and implement this next-generation software solution. © 2014 Society for Laboratory Automation and Screening.

  6. Revaluation of biological variation of glycated hemoglobin (HbA(1c)) using an accurately designed protocol and an assay traceable to the IFCC reference system.

    Science.gov (United States)

    Braga, Federica; Dolci, Alberto; Montagnana, Martina; Pagani, Franca; Paleari, Renata; Guidi, Gian Cesare; Mosca, Andrea; Panteghini, Mauro

    2011-07-15

    Glycated hemoglobin (HbA(1c)) has a key role for diagnosing diabetes and monitoring glycemic state. As recently reviewed, available data on HbA(1c) biological variation show marked heterogeneity. Here we experimentally revaluated these data using a well designed protocol. We took five EDTA whole blood specimens from 18 apparently healthy subjects on the same day, every two weeks for two months. Samples were stored at -80°C until analysis and assayed in duplicate in a single run by Roche Tina-quant® Gen.2 immunoassay. Data were analyzed by the ANOVA. To assess the assay traceability to the IFCC reference method, we preliminarily carried out a correlation experiment. The bias (mean±SD) of the Roche immunoassay was 0.3%±0.7%, confirming the traceability of the employed assay. No difference was found in HbA(1c) values between men and women. Within- and between-subject CV were 2.5% and 7.1%, respectively. Derived desirable analytical goals for imprecision, bias, and total error resulted 1.3%, 1.9%, and 3.9%, respectively. HbA(1c) had marked individuality, limiting the use of population-based reference limits for test interpretation. The estimated critical difference was ~10%. For the first time we defined biological variation and derived indices for the clinical application of HbA(1c) measurements using an accurately designed protocol and an assay standardized according to the IFCC. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Structure-Based Design: Synthesis, X-ray Crystallography, and Biological Evaluation of N-Substituted-4-Hydroxy-2-Quinolone-3-Carboxamides as Potential Cytotoxic Agents.

    Science.gov (United States)

    Sabbah, Dima A; Hishmah, Bayan; Sweidan, Kamal; Bardaweel, Sanaa; AlDamen, Murad; Zhong, Haizhen A; Abu Khalaf, Reema; Hasan Ibrahim, Ameerah; Al-Qirim, Tariq; Abu Sheikha, Ghassan; Mubarak, Mohammad S

    2018-01-01

    Oncogenic potential of phosphatidylinositol 3-kinase (PI3Kα) has been highlighted as a therapeutic target for anticancer drug design. Target compounds were designed to address the effect of different substitution patterns at the N atom of the carboxamide moiety on the bioactivity of this series. Synthesis of the targeted compounds, crystallography, biological evaluation tests against human colon carcinoma (HCT-116), and Glide docking studies. A new series of N-substituted- 4-hydroxy-2-quinolone-3-carboxamides was prepared and characterized by means of FT-IR, 1H and 13C NMR, and elemental analysis. In addition, the identity of the core nucleus 5 was successfully characterized with the aid of X-ray crystallography. Biological activity of prepared compounds was investigated in vitro against human colon carcinoma (HCT-116) cell line. Results revealed that these compounds inhibit cell proliferation and induce apoptosis through an increase in caspase-3 activity and a decrease in DNA cellular content. Compounds 7, 14, and 17 which have H-bond acceptor moiety on p-position displayed promising PI3Kα inhibitory activity. On the other hand, derivatives tailored with bulky and hydrophobic motifs (16 and 18) on o- and m-positions exhibited moderate activity. Molecular docking studies against PI3Kα and caspase-3 showed an agreement between the predicted binding affinity (ΔGobsd) and IC50 values of the derivatives for the caspase-3 model. Furthermore, Glide docking studies against PI3Kα demonstrated that the newly synthesized compounds accommodate PI3Kα kinase catalytic domain and form H-bonding with key binding residues. The series exhibited a potential PI3Kα inhibitory activity in HCT-116 cell line. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Design of Recombinant Stem Cell Factor macrophage Colony Stimulating Factor Fusion Proteins and their Biological Activity In Vitro

    Science.gov (United States)

    Chen, Tao; Yang, Jie; Wang, Yuelang; Zhan, Chenyang; Zang, Yuhui; Qin, Junchuan

    2005-05-01

    Stem cell factor (SCF) and macrophage colony stimulating factor (M-CSF) can act in synergistic way to promote the growth of mononuclear phagocytes. SCF-M-CSF fusion proteins were designed on the computer using the Homology and Biopolymer modules of the software packages InsightII. Several existing crystal structures were used as templates to generate models of the complexes of receptor with fusion protein. The structure rationality of the fusion protein incorporated a series of flexible linker peptide was analyzed on InsightII system. Then, a suitable peptide GGGGSGGGGSGG was chosen for the fusion protein. Two recombinant SCF-M-CSF fusion proteins were generated by construction of a plasmid in which the coding regions of human SCF (1-165aa) and M-CSF (1-149aa) cDNA were connected by this linker peptide coding sequence followed by subsequent expression in insect cell. The results of Western blot and activity analysis showed that these two recombinant fusion proteins existed as a dimer with a molecular weight of 84 KD under non-reducing conditions and a monomer of 42 KD at reducing condition. The results of cell proliferation assays showed that each fusion protein induced a dose-dependent proliferative response. At equimolar concentration, SCF/M-CSF was about 20 times more potent than the standard monomeric SCF in stimulating TF-1 cell line growth, while M-CSF/SCF was 10 times of monomeric SCF. No activity difference of M-CSF/SCF or SCF/M-CSF to M-CSF (at same molar) was found in stimulating the HL-60 cell linear growth. The synergistic effect of SCF and M-CSF moieties in the fusion proteins was demonstrated by the result of clonogenic assay performed with human bone mononuclear, in which both SCF/M-CSF and M-CSF/SCF induced much higher number of CFU-M than equimolar amount of SCF or M-CSF or that of two cytokines mixture.

  9. 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)

  10. Using biological and physico-chemical test methods to assess the role of concrete mixture design in resistance to microbially induced corrosion

    Science.gov (United States)

    House, Mitchell Wayne

    to evaluate performance of concrete specimens under conditions designed to accelerate MIC. Concrete specimens representing 12 mixture designs were inoculated with 5 species of Thiobacillus bacteria and placed in a biological growth chamber designed to encourage bacterial growth and sulfuric acid production by optimizing temperature, delivering necessary nutrients, and providing hydrogen sulfide gas. Results indicate that using supplementary cementitious materials, limestone aggregates, and sulfate resistant cement can improve resistance to MIC. It is interesting to note that this study showed that unlike many other durability problems the role of water to cement ratio was unclear. The second method presented is a sulfuric acid immersion study designed to evaluate the resistance of 12 concrete mixture designs to 5 concentrations of sulfuric acid. Experimental protocols (like those in ASTM) previously considered trivial were found to have a dramatic effect on experimental results. It was found that using supplementary cementitious materials, limestone coarse aggregate, and sulfate resistant cement can increase concrete resistance to moderate sulfuric acid concentrations. The primary damage mechanism was observed to change depending on sulfuric acid concentration. Rapid deterioration of specimens exposed to aggressive sulfuric acid solutions indicates that degradation of concrete under the most severe MIC conditions (i.e., a pH concrete mixture proportions. A holistic approach is needed for these situations that considers environmental conditions as well.

  11. Biological Agents

    Science.gov (United States)

    ... E-Tools Safety and Health Topics / Biological Agents Biological Agents This page requires that javascript be enabled ... 202) 693-2300 if additional assistance is required. Biological Agents Menu Overview In Focus: Ebola Frederick A. ...

  12. Design

    DEFF Research Database (Denmark)

    Volf, Mette

    Design - proces & metode iBog®  er enestående i sit fokus på afmystificering og operationalisering af designprocessens flygtige og komplekse karakter. Udgivelsen går bag om designerens daglige arbejde og giver et indblik i den kreative skabelsesproces, som designeren er en del af. Udover et bredt...... indblik i designerens arbejdsmetoder og designparametre giver Design - proces & metode en række eksempler fra anerkendte designvirksomheder, der gør det muligt at komme helt tæt på designerens virkelighed....

  13. Design

    Science.gov (United States)

    Buchanan, Richard; Cross, Nigel; Durling, David; Nelson, Harold; Owen, Charles; Valtonen, Anna; Boling, Elizabeth; Gibbons, Andrew; Visscher-Voerman, Irene

    2013-01-01

    Scholars representing the field of design were asked to identify what they considered to be the most exciting and imaginative work currently being done in their field, as well as how that work might change our understanding. The scholars included Richard Buchanan, Nigel Cross, David Durling, Harold Nelson, Charles Owen, and Anna Valtonen. Scholars…

  14. 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.

  15. Taguchi Experimental Design for Optimization of Recombinant Human Growth Hormone Production in CHO Cell Lines and Comparing its Biological Activity with Prokaryotic Growth Hormone.

    Science.gov (United States)

    Aghili, Zahra Sadat; Zarkesh-Esfahani, Sayyed Hamid

    2018-02-01

    Growth hormone deficiency results in growth retardation in children and the GH deficiency syndrome in adults and they need to receive recombinant-GH in order to rectify the GH deficiency symptoms. Mammalian cells have become the favorite system for production of recombinant proteins for clinical application compared to prokaryotic systems because of their capability for appropriate protein folding, assembly, post-translational modification and proper signal. However, production level in mammalian cells is generally low compared to prokaryotic hosts. Taguchi has established orthogonal arrays to describe a large number of experimental situations mainly to reduce experimental errors and to enhance the efficiency and reproducibility of laboratory experiments.In the present study, rhGH was produced in CHO cells and production of rhGH was assessed using Dot blotting, western blotting and Elisa assay. For optimization of rhGH production in CHO cells using Taguchi method An M16 orthogonal experimental design was used to investigate four different culture components. The biological activity of rhGH was assessed using LHRE-TK-Luciferase reporter gene system in HEK-293 and compared to the biological activity of prokaryotic rhGH.A maximal productivity of rhGH was reached in the conditions of 1%DMSO, 1%glycerol, 25 µM ZnSO 4 and 0 mM NaBu. Our findings indicate that control of culture conditions such as the addition of chemical components helps to develop an efficient large-scale and industrial process for the production of rhGH in CHO cells. Results of bioassay indicated that rhGH produced by CHO cells is able to induce GH-mediated intracellular cell signaling and showed higher bioactivity when compared to prokaryotic GH at the same concentrations. © Georg Thieme Verlag KG Stuttgart · New York.

  16. Design, Synthesis and Biological Evaluation of Histone Deacetylase (HDAC) Inhibitors: Saha (Vorinostat) Analogs and Biaryl Indolyl Benzamide Inhibitors Display Isoform Selectivity

    Science.gov (United States)

    Negmeldin, Ahmed Thabet

    HDAC proteins have emerged as interesting targets for anti-cancer drugs due to their involvement in cancers, as well as several other diseases. Several HDAC inhibitors have been approved by the FDA as anti-cancer drugs, including SAHA (suberoylanilide hydroxamic acid, Vorinostat). Unfortunately, SAHA inhibits most HDAC isoforms, which limit its use as a pharmacological tool and may lead to side effects in the clinic. In this work we were interested in developing isoform selective HDAC inhibitors, which may decrease or eliminate the side effects associated with non-selective inhibitors treatment. In addition, isoform selective HDAC inhibitors can be used as biological tools to help understand the HDAC-related cancer biology. Our strategy was based on synthesis and screening of several derivatives of the non-selective FDA approved drug SAHA substituted at different positions of the linker region. Several SAHA analogs modified at the C4 and C5 positions of the linker were synthesized. The new C4- and C5-modified SAHA libraries, along with the previously synthesized C2-modified SAHA analogs were screened in vitro and in cellulo for HDAC isoform selectivity. Interestingly, several analogs exhibited dual HDAC6/HDAC8 selectivity. Enantioselective syntheses of the pure enantiomers of some of the interesting analogs were performed and the enantiomers were screened in vitro. Among the most interesting analogs, ( R)-C4-benzyl SAHA displayed 520- to 1300-fold selectivity for HDAC6 and HDAC8 over HDAC1, 2, and 3, with IC50 values of 48 and 27 nM with HDAC6 and 8, respectively. Docking studies were performed to provide structural rationale for the observed selectivity of the new analogs. In addition, rational design, synthesis, and screening of several other biaryl indolyl benzamide HDAC inhibitors is discussed, and some showed modest HDAC1 selectivity. The new biaryl indolyl benzamides can be useful to further develop HDAC1 selective inhibitors. The dual HDAC6/8 selective

  17. Biological Clocks & Circadian Rhythms

    Science.gov (United States)

    Robertson, Laura; Jones, M. Gail

    2009-01-01

    The study of biological clocks and circadian rhythms is an excellent way to address the inquiry strand in the National Science Education Standards (NSES) (NRC 1996). Students can study these everyday phenomena by designing experiments, gathering and analyzing data, and generating new experiments. As students explore biological clocks and circadian…

  18. Factorial design of essential oil extraction from Fagraea fragrans Roxb. flowers and evaluation of its biological activities for perfumery and cosmetic applications.

    Science.gov (United States)

    Yingngam, B; Brantner, A H

    2015-06-01

    To optimize the extraction yields of essential oil from Fagraea fragrans Roxb. flowers in hydro-distillation using a central composite design (CCD) and to evaluate its biological activities for perfumery and cosmetic applications. Central composite design was applied to study the influences of operational parameters [water to flower weight (X(1)) and distillation time (X(2))] on the yields of essential oil (Y). Chemical compositions of the essential oil extracted from the optimized condition were identified by gas chromatography-mass spectrometry. Antioxidant activities of the essential oil were determined against ABTS(•+) and DPPH(•) radicals, and the cytotoxic effects were assessed on human embryonic kidney (HEK293) cells by the use of the MTT assay. Also, the aromatic properties of the essential oil were evaluated by five healthy trained volunteers. The best conditions to obtain the maximum essential oil yield were 7.5 mL g(-1) (X(1)) and 215 min (X(2)). The experimental yield of the essential oil (0.35 ± 0.02% v/w) was close to the value predicted by a mathematical model (0.35 ± 0.01% v/w). 3-Octadecyne, Z,Z,Z-7,10,13-hexadecatrienal, E-nerolidol, pentadecanal and linalool were the major constituents of the essential oil. The essential oil showed moderate antioxidant capacities with no toxic effects on HEK293 cells at 1-250 μg mL(-1). Also, the essential oil exhibited a very strong aroma and was classified to be top- to middle-notes. The results offer the effectively operational conditions in the extraction of essential oil from F. fragrans using hydro-distillation. The essential oil could be used as a natural fragrance, having antioxidant activity with slight cytotoxicity, for perfumery and cosmetic applications. © 2014 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  19. Design and biological functionality of a novel hybrid Ti-6Al-4V/hydrogel system for reconstruction of bone defects.

    Science.gov (United States)

    Kumar, Alok; Nune, K C; Misra, R D K

    2018-04-01

    We have designed a unique injectable bioactive hydrogel comprising of alginate, gelatin, and nanocrystalline hydroxyapatite and loaded with osteoblasts, with the ability to infiltrate into three-dimensional Ti-6Al-4V scaffolds with interconnected porous architecture, fabricated by electron beam melting. A two-step crosslinking process using the EDC/NHS and CaCl 2 was adopted and found to be effective in the fabrication of cell-loaded hydrogel/Ti-6Al-4V scaffold system. This hybrid Ti-6Al-4V scaffold/hydrogel system was designed for the reconstruction of bone defects, which are difficult to heal in the absence of suitable support materials. The hybrid Ti-6Al-4V/hydrogel system favourably modulated the biological functions, namely, adhesion, proliferation, cell-to-cell, and cell-material communication because of the presence of extracellular matrix-like hydrogel in the interconnected porous structure of 3D printed Ti-6Al-4V scaffold. The hydrogel was cytocompatible, which was proven through live/dead assay, the expression level of prominent proteins for cell adhesion and cytoskeleton, including 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay. Furthermore, the high bone formation ability of the hydrogel was confirmed using alkaline phosphatase assay. A high equilibrium water content (~97%) in the hydrogel enables the delivery of cells and bioactive molecules, necessary for bone tissue growth. Although not studied, the presence of hydrogel in the pores of the scaffold can provide the space for the cell migration as well as vascularization through it, required for the effective exchange of nutrients. In conclusion, we underscore that the 3D-printed Ti-6Al-4V scaffold-loaded with bioactive hydrogel to treat the bone defects significantly impacted cellular functions and cell-material interaction. Copyright © 2017 John Wiley & Sons, Ltd.

  20. Novel multi-target-directed ligands for Alzheimer's disease: Combining cholinesterase inhibitors and 5-HT6 receptor antagonists. Design, synthesis and biological evaluation.

    Science.gov (United States)

    Więckowska, Anna; Kołaczkowski, Marcin; Bucki, Adam; Godyń, Justyna; Marcinkowska, Monika; Więckowski, Krzysztof; Zaręba, Paula; Siwek, Agata; Kazek, Grzegorz; Głuch-Lutwin, Monika; Mierzejewski, Paweł; Bienkowski, Przemysław; Sienkiewicz-Jarosz, Halina; Knez, Damijan; Wichur, Tomasz; Gobec, Stanislav; Malawska, Barbara

    2016-11-29

    As currently postulated, a complex treatment may be key to an effective therapy for Alzheimer's disease (AD). Recent clinical trials in patients with moderate AD have shown a superior effect of the combination therapy of donepezil (a selective acetylcholinesterase inhibitor) with idalopirdine (a 5-HT 6 receptor antagonist) over monotherapy with donepezil. Here, we present the first report on the design, synthesis and biological evaluation of a novel class of multifunctional ligands that combines a 5-HT 6 receptor antagonist with a cholinesterase inhibitor. Novel multi-target-directed ligands (MTDLs) were designed by combining pharmacophores directed against the 5-HT 6 receptor (1-(phenylsulfonyl)-4-(piperazin-1-yl)-1H-indole) and cholinesterases (tacrine or N-benzylpiperidine analogues). In vitro evaluation led to the identification of tacrine derivative 12 with well-balanced potencies against the 5-HT 6 receptor (K b  = 27 nM), acetylcholinesterase and butyrylcholinesterase (IC 50 hAChE  = 12 nM, IC 50 hBuChE  = 29 nM). The compound also showed good in vitro blood-brain-barrier permeability (PAMPA-BBB assay), which was confirmed in vivo (open field study). Central cholinomimetic activity was confirmed in vivo in rats using a scopolamine-induced hyperlocomotion model. A novel class of multifunctional ligands with compound 12 as the best derivative in a series represents an excellent starting point for the further development of an effective treatment for AD. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  1. Design, synthesis and biological evaluations of N-Hydroxy thienopyrimidine-2,4-diones as inhibitors of HIV reverse transcriptase-associated RNase H.

    Science.gov (United States)

    Kankanala, Jayakanth; Kirby, Karen A; Huber, Andrew D; Casey, Mary C; Wilson, Daniel J; Sarafianos, Stefan G; Wang, Zhengqiang

    2017-12-01

    Human immunodeficiency virus (HIV) reverse transcriptase (RT) associated ribonuclease H (RNase H) is the only HIV enzymatic function not targeted by current antiviral drugs. Although various chemotypes have been reported to inhibit HIV RNase H, few have shown significant antiviral activities. We report herein the design, synthesis and biological evaluation of a novel N-hydroxy thienopyrimidine-2,3-dione chemotype (11) which potently and selectively inhibited RNase H with considerable potency against HIV-1 in cell culture. Current structure-activity-relationship (SAR) identified analogue 11d as a nanomolar inhibitor of RNase H (IC 50  = 0.04 μM) with decent antiviral potency (EC 50  = 7.4 μM) and no cytotoxicity (CC 50  > 100 μM). In extended biochemical assays compound 11d did not inhibit RT polymerase (pol) while inhibiting integrase strand transfer (INST) with 53 fold lower potency (IC 50  = 2.1 μM) than RNase H inhibition. Crystallographic and molecular modeling studies confirmed the RNase H active site binding mode. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  2. A Western blot-based investigation of the yeast secretory pathway designed for an intermediate-level undergraduate cell biology laboratory.

    Science.gov (United States)

    Hood-Degrenier, Jennifer K

    2008-01-01

    The movement of newly synthesized proteins through the endomembrane system of eukaryotic cells, often referred to generally as the secretory pathway, is a topic covered in most intermediate-level undergraduate cell biology courses. An article previously published in this journal described a laboratory exercise in which yeast mutants defective in two distinct steps of protein secretion were differentiated using a genetic reporter designed specifically to identify defects in the first step of the pathway, the insertion of proteins into the endoplasmic reticulum (Vallen, 2002). We have developed two versions of a Western blotting assay that serves as a second way of distinguishing the two secretory mutants, which we pair with the genetic assay in a 3-wk laboratory module. A quiz administered before and after students participated in the lab activities revealed significant postlab gains in their understanding of the secretory pathway and experimental techniques used to study it. A second survey administered at the end of the lab module assessed student perceptions of the efficacy of the lab activities; the results of this survey indicated that the experiments were successful in meeting a set of educational goals defined by the instructor.

  3. Severe Acute Respiratory Syndrome-Coronavirus Papain-Like Novel Protease Inhibitors: Design, Synthesis, Protein-Ligand X-ray Structure and Biological Evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, Arun K.; Takayama, Jun; Rao, Kalapala Venkateswar; Ratia, Kiira; Chaudhuri, Rima; Mulhearn, Debbie C.; Lee, Hyun; Nichols, Daniel B.; Baliji, Surendranath; Baker, Susan C.; Johnson, Michael E.; Mesecar, Andrew D. (Purdue); (UC); (UIC)

    2012-02-21

    The design, synthesis, X-ray crystal structure, molecular modeling, and biological evaluation of a series of new generation SARS-CoV PLpro inhibitors are described. A new lead compound 3 (6577871) was identified via high-throughput screening of a diverse chemical library. Subsequently, we carried out lead optimization and structure-activity studies to provide a series of improved inhibitors that show potent PLpro inhibition and antiviral activity against SARS-CoV infected Vero E6 cells. Interestingly, the (S)-Me inhibitor 15h (enzyme IC{sub 50} = 0.56 {mu}M; antiviral EC{sub 50} = 9.1 {mu}M) and the corresponding (R)-Me 15g (IC{sub 50} = 0.32 {mu}M; antiviral EC{sub 50} = 9.1 {mu}M) are the most potent compounds in this series, with nearly equivalent enzymatic inhibition and antiviral activity. A protein-ligand X-ray structure of 15g-bound SARS-CoV PLpro and a corresponding model of 15h docked to PLpro provide intriguing molecular insight into the ligand-binding site interactions.

  4. The "Performance of Rotavirus and Oral Polio Vaccines in Developing Countries" (PROVIDE) study: description of methods of an interventional study designed to explore complex biologic problems.

    Science.gov (United States)

    Kirkpatrick, Beth D; Colgate, E Ross; Mychaleckyj, Josyf C; Haque, Rashidul; Dickson, Dorothy M; Carmolli, Marya P; Nayak, Uma; Taniuchi, Mami; Naylor, Caitlin; Qadri, Firdausi; Ma, Jennie Z; Alam, Masud; Walsh, Mary Claire; Diehl, Sean A; Petri, William A

    2015-04-01

    Oral vaccines appear less effective in children in the developing world. Proposed biologic reasons include concurrent enteric infections, malnutrition, breast milk interference, and environmental enteropathy (EE). Rigorous study design and careful data management are essential to begin to understand this complex problem while assuring research subject safety. Herein, we describe the methodology and lessons learned in the PROVIDE study (Dhaka, Bangladesh). A randomized clinical trial platform evaluated the efficacy of delayed-dose oral rotavirus vaccine as well as the benefit of an injectable polio vaccine replacing one dose of oral polio vaccine. This rigorous infrastructure supported the additional examination of hypotheses of vaccine underperformance. Primary and secondary efficacy and immunogenicity measures for rotavirus and polio vaccines were measured, as well as the impact of EE and additional exploratory variables. Methods for the enrollment and 2-year follow-up of a 700 child birth cohort are described, including core laboratory, safety, regulatory, and data management practices. Intense efforts to standardize clinical, laboratory, and data management procedures in a developing world setting provide clinical trials rigor to all outcomes. Although this study infrastructure requires extensive time and effort, it allows optimized safety and confidence in the validity of data gathered in complex, developing country settings. © The American Society of Tropical Medicine and Hygiene.

  5. Design

    DEFF Research Database (Denmark)

    Jensen, Ole B.; Pettiway, Keon

    2017-01-01

    In this chapter, Ole B. Jensen takes a situational approach to mobilities to examine how ordinary life activities are structured by technology and design. Using “staging mobilities” as a theoretical approach, Jensen considers mobilities as overlapping, actions, interactions and decisions by desig...... by providing ideas about future research for investigating mobilities in situ as a kind of “staging,” which he notes is influenced by the “material turn” in social sciences....... with a brief description of how movement is studied within social sciences after the “mobilities turn” versus the idea of physical movement in transport geography and engineering. He then explains how “mobilities design” was derived from connections between traffic and architecture. Jensen concludes...

  6. Process Design and Economics for the Conversion of Lignocellulosic Biomass to Hydrocarbons: Dilute-Acid and Enzymatic Deconstruction of Biomass to Sugars and Biological Conversion of Sugars to Hydrocarbons

    Energy Technology Data Exchange (ETDEWEB)

    Davis, R.; Tao, L.; Tan, E. C. D.; Biddy, M. J.; Beckham, G. T.; Scarlata, C.; Jacobson, J.; Cafferty, K.; Ross, J.; Lukas, J.; Knorr, D.; Schoen, P.

    2013-10-01

    This report describes one potential conversion process to hydrocarbon products by way of biological conversion of lingnocellulosic-dervied sugars. The process design converts biomass to a hydrocarbon intermediate, a free fatty acid, using dilute-acid pretreatement, enzymatic saccharification, and bioconversion. Ancillary areas--feed handling, hydrolysate conditioning, product recovery and upgrading (hydrotreating) to a final blendstock material, wastewater treatment, lignin combusion, and utilities--are also included in the design.

  7. [Design and biological evaluation of poly-lactic-co-glycolic acid (PLGA) mesh/collagen-chitosan hybrid scaffold (CCS) as a dermal substitute].

    Science.gov (United States)

    Wang, Xin-Gang; You, Chuan-Gang; Sun, Hua-Feng; Hu, Xin-Lei; Han, Chun-Mao; Zhang, Li-Ping; Zheng, Yu-Rong; Li, Qi-Yin

    2011-02-01

    To design and construct a kind of dermal regeneration template with mesh, and to preliminarily evaluate its biological characteristics. PLGA mesh was integrated into CCS with freeze-drying method for constructing PLGA mesh/CCS composite (PCCS). The micromorphologies and mechanical properties among PLGA mesh, CCS, and PCCS were compared. PCCS and CCS was respectively implanted into subcutaneous tissue of SD rats (PCCS and CCS groups, 9 rats in each group). The tissue samples were collected at post operation week (POW) 1, 2, and 4 for histopathological and immunohistochemical observation. Protein levels of CD68, MPO, IL-1beta, IL-10 were examined by Western blot, with expression of gray value. Data were processed with one-way analysis of variance and t test. Three-dimensional porous structure of PCCS was similar to that of CCS. Mechanical property of PLGA mesh and PCCS was respectively (3.07 +/- 0.10), (3.26 +/- 0.15) MPa, and they were higher than that of CCS [(0.42 +/- 0.21) MPa, F = 592.3, P CCS group were observed at POW 4. A large accumulation of macrophages was observed in both groups, especially at POW 2, and more macrophage infiltration was observed in CCS group. The protein level of IL-10 in PCCS group at POW 2 was obviously higher than that in CCS group, while the protein levels of CD68, MPO, IL-1beta were significantly decreased as compared with those in CCS group (with t value from -4.06 to 2.89, P < 0.05 or P < 0.01). PCCS has excellent mechanical property with appropriate three-dimensional porous structure. Meanwhile, it can rapidly induce formation of new tissue and vascularization, and it has a prospect of serving as a dermal substitute.

  8. Chimeric design, synthesis, and biological assays of a new nonpeptide insulin-mimetic vanadium compound to inhibit protein tyrosine phosphatase 1B.

    Science.gov (United States)

    Scior, Thomas; Guevara-García, José Antonio; Melendez, F J; Abdallah, Hassan H; Do, Quoc-Tuan; Bernard, Philippe

    2010-09-24

    Prior to its total synthesis, a new vanadium coordination compound, called TSAG0101, was computationally designed to inhibit the enzyme protein tyrosine phosphatase 1B (PTP1B). The PTP1B acts as a negative regulator of insulin signaling by blocking the active site where phosphate hydrolysis of the insulin receptor takes place. TSAG001, [V(V)O(2)(OH)(picolinamide)], was characterized by infrared (IR) and nuclear magnetic resonance (NMR) spectroscopy; IR: ν/cm(-1) 3,570 (NH), 1,627 (C=O, coordinated), 1,417 (C-N), 970/842 (O=V=O), 727 δ̣ (pyridine ring); (13)C NMR: 5 bands between 122 and 151 ppm and carbonyl C shifted to 180 ppm; and (1)H NMR: 4 broad bands from 7.6 to 8.2 ppm and NH(2) shifted to 8.8 ppm. In aqueous solution, in presence or absence of sodium citrate as a biologically relevant and ubiquitous chelator, TSAG0101 undergoes neither ligand exchange nor reduction of its central vanadium atom during 24 hours. TSAG0101 shows blood glucose lowering effects in rats but it produced no alteration of basal- or glucose-induced insulin secretion on β cells during in vitro tests, all of which excludes a direct mechanism evidencing the extrapancreatic nature of its activity. The lethal dose (LD(50)) of TSAG0101 was determined in Wistar mice yielding a value of 412 mg/kg. This value is one of the highest among vanadium compounds and classifies it as a mild toxicity agent when compared with literature data. Due to its nonsubstituted, small-sized scaffold design, its remarkable complex stability, and low toxicity; TSAG0101 should be considered as an innovative insulin-mimetic principle with promising properties and, therefore, could become a new lead compound for potential nonpeptide PTP1B inhibitors in antidiabetic drug research. In view of the present work, the inhibitory concentration (IC(50)) and extended solution stability will be tested.

  9. Developmental engineering: a new paradigm for the design and manufacturing of cell-based products. Part II: from genes to networks: tissue engineering from the viewpoint of systems biology and network science.

    Science.gov (United States)

    Lenas, Petros; Moos, Malcolm; Luyten, Frank P

    2009-12-01

    The field of tissue engineering is moving toward a new concept of "in vitro biomimetics of in vivo tissue development." In Part I of this series, we proposed a theoretical framework integrating the concepts of developmental biology with those of process design to provide the rules for the design of biomimetic processes. We named this methodology "developmental engineering" to emphasize that it is not the tissue but the process of in vitro tissue development that has to be engineered. To formulate the process design rules in a rigorous way that will allow a computational design, we should refer to mathematical methods to model the biological process taking place in vitro. Tissue functions cannot be attributed to individual molecules but rather to complex interactions between the numerous components of a cell and interactions between cells in a tissue that form a network. For tissue engineering to advance to the level of a technologically driven discipline amenable to well-established principles of process engineering, a scientifically rigorous formulation is needed of the general design rules so that the behavior of networks of genes, proteins, or cells that govern the unfolding of developmental processes could be related to the design parameters. Now that sufficient experimental data exist to construct plausible mathematical models of many biological control circuits, explicit hypotheses can be evaluated using computational approaches to facilitate process design. Recent progress in systems biology has shown that the empirical concepts of developmental biology that we used in Part I to extract the rules of biomimetic process design can be expressed in rigorous mathematical terms. This allows the accurate characterization of manufacturing processes in tissue engineering as well as the properties of the artificial tissues themselves. In addition, network science has recently shown that the behavior of biological networks strongly depends on their topology and has

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

    Science.gov (United States)

    Chao, Ran; Yuan, YongBo; Zhao, HuiMin

    2015-07-01

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

  11. Mathematical biology

    CERN Document Server

    Murray, James D

    1993-01-01

    The book is a textbook (with many exercises) giving an in-depth account of the practical use of mathematical modelling in the biomedical sciences. The mathematical level required is generally not high and the emphasis is on what is required to solve the real biological problem. The subject matter is drawn, e.g. from population biology, reaction kinetics, biological oscillators and switches, Belousov-Zhabotinskii reaction, reaction-diffusion theory, biological wave phenomena, central pattern generators, neural models, spread of epidemics, mechanochemical theory of biological pattern formation and importance in evolution. Most of the models are based on real biological problems and the predictions and explanations offered as a direct result of mathematical analysis of the models are important aspects of the book. The aim is to provide a thorough training in practical mathematical biology and to show how exciting and novel mathematical challenges arise from a genuine interdisciplinary involvement with the biosci...

  12. Learning Biology with Plant Pathology.

    Science.gov (United States)

    Carroll, Juliet E.

    This monograph contains 10 plant pathology experiments that were written to correspond to portions of a biology curriculum. Each experiment is suitable to a biology topic and designed to encourage exploration of those biological concepts being taught. Experiments include: (1) The Symptoms and Signs of Disease; (2) Koch's Postulates; (3)…

  13. BIOLOGY AND CPUE SPATIAL DISTRIBUTION OF ESCOLAR Lepidocybium flavobrunneum (Smith, 1843 IN EASTERN INDIAN OCEAN (EVOLVING FISHERIES: TODAY’S BY-CATCH IS TOMORROW’S TARGET CATCH

    Directory of Open Access Journals (Sweden)

    Fathur Rochman

    2016-12-01

    Full Text Available Discharge of by catch is a significant problem in world fishery. Every commercial fishery such as tuna longline has a suite of bycatch species, escolar fish (LEC. LEC as by catch product has received a little attention because of its lower economic value and given its importance as a secondary market. With time, however, market can become establish for this presently undesirable species. Acknowledging that today’s by catch might become tomorrow’s target fish. The aims of this study areto provide information on biological aspect and catch per unit of effort (CPUE spatial distribution of escolar (Lepidocybium flavobrunneum as by catch in Indonesian longline fishery operating in the Eastern Indian Ocean. Total escolar samples of 1,815 were taken from scientific observer data from 2011-2013. The study area of escolar was between 0.897-33.175°S and 85.366– 138.733°E of Eastern Indian Ocean. Results show that the escolar length (cmFL is distributed from 27-178 cmFL (median=83 cmFL, mode=85 cmFL, mean=83.95 cmFL and n= 1.812 and dominated by the size of 85 cmFL. The length weight relationship was determined to be W=0.0002FL2.2926(W in kg, FL in cm. In terms of CPUEs distribution, the lower CPUEs(1.0001 to 7.382 generally occurred in Western Australian, precisely on grid between 10-35°S and 85-110°E. These grids would be a potential for fishing LEC with the best time to catch in June to August.

  14. 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.

  15. Using an Adoption–Biological Family Design to Examine Associations Between Maternal Trauma, Maternal Depressive Symptoms, and Child Internalizing and Externalizing Behaviors

    Science.gov (United States)

    Grabow, Aleksandria Perez; Khurana, Atika; Natsuaki, Misaki N.; Neiderhiser, Jenae M.; Harold, Gordon T.; Shaw, Daniel S.; Ganiban, Jody M.; Reiss, David; Leve, Leslie D.

    2017-01-01

    Maternal trauma is a complex risk factor that has been linked to adverse child outcomes, yet the mechanisms underlying this association are not well understood. This study, which included adoptive and biological families, examined the heritable and environmental mechanisms by which maternal trauma and associated depressive symptoms are linked to child internalizing and externalizing behaviors. Path analyses were used to analyze data from 541 adoptive mother–adopted child (AM–AC) dyads and 126 biological mother–biological child (BM–BC) dyads; the two family types were linked through the same biological mother. Rearing mother’s trauma was associated with child internalizing and externalizing behaviors in AM–AC and BM–BC dyads, and this association was mediated by rearing mothers’ depressive symptoms, with the exception of biological child externalizing behavior, for which biological mother trauma had a direct influence only. Significant associations between maternal trauma and child behavior in dyads that share only environment (i.e., AM–AC dyads) suggest an environmental mechanism of influence for maternal trauma. Significant associations were also observed between maternal depressive symptoms and child internalizing and externalizing behavior in dyads that were only genetically related, with no shared environment (i.e., BM–AC dyads), suggesting a heritable pathway of influence via maternal depressive symptoms. PMID:29162177

  16. Synthetic Biology: Putting Synthesis into Biology

    Science.gov (United States)

    Liang, Jing; Luo, Yunzi; Zhao, Huimin

    2010-01-01

    The ability to manipulate living organisms is at the heart of a range of emerging technologies that serve to address important and current problems in environment, energy, and health. However, with all its complexity and interconnectivity, biology has for many years been recalcitrant to engineering manipulations. The recent advances in synthesis, analysis, and modeling methods have finally provided the tools necessary to manipulate living systems in meaningful ways, and have led to the coining of a field named synthetic biology. The scope of synthetic biology is as complicated as life itself – encompassing many branches of science, and across many scales of application. New DNA synthesis and assembly techniques have made routine the customization of very large DNA molecules. This in turn has allowed the incorporation of multiple genes and pathways. By coupling these with techniques that allow for the modeling and design of protein functions, scientists have now gained the tools to create completely novel biological machineries. Even the ultimate biological machinery – a self-replicating organism – is being pursued at this moment. It is the purpose of this review to dissect and organize these various components of synthetic biology into a coherent picture. PMID:21064036

  17. Neutron structural biology

    International Nuclear Information System (INIS)

    Schoenborn, B.

    1997-01-01

    This is the final report of a one-year, Laboratory Directed Research and Development (LDRD) project at Los Alamos National Laboratory (LANL). We investigated design concepts of neutron scattering capabilities for structural biology at spallation sources. This included the analysis of design parameters for protein crystallography as well as membrane diffraction instruments. These instruments are designed to be general user facilities and will be used by scientists from industry, universities, and other national laboratories

  18. Rational Design and Synthesis of Biologically Active Disubstituted 2(3H) Furanones and Pyrrolone Derivatives as Potent and Safer Non Steroidal Anti-inflammatory Agents.

    Science.gov (United States)

    Khokra, S L; Khan, S A; Choudhary, D; Hasan, S M; Ahmad, A; Husain, Asif

    2016-01-01

    Furanone and pyrrolone heterocyclic ring system represent important and interesting classes of bioactive compounds. Medicinal chemists use these heterocycyclic moieties as scaffolds in drug design and discovery. A series of 3-arylidene-5-(naphthalene-2-yl)-furan-2(3H)-ones (2a-j) were synthesized by incorporating pharmacophore of COX-2 inhibitor rofecoxib and naphthyl ring of naproxen as potential non steroidal anti-inflammatory agents. These furanone derivatives were subsequently reacted with dry ammonia gas and benzylamine to furnish corresponding 3-arylidene-5-(naphthlen-2-yl)-1H-pyrrol-2(3H)-ones (3a-e) and 3-arylidene-1-benzyl-5- (naphthalene-2-yl)-1H-pyrrol-2(3H)-ones (4a-e), respectively. The newly prepared heterocyclics were screened for their expected in-vivo biological activities including anti-inflammatory, analgesic and ulcerogenic actions in rodents. The COX-2 inhibitory behavior of synthesized compounds was also assessed via automated docking studies. The chemical structure of the synthesized compounds was characterized by using modern spectroscopic techniques. Result of in-vivo pharmacological studies demonstrated that almost all N-Benzyl-pyrrol-2(3H)-ones (4a-e) showed better anti-inflammatory and analgesic activities in comparison with the other two series of furan-2(3H)-ones and pyrrol- 2(3H)-ones. The moldock score value of the tested compounds was found in the range of -116.66 to -170.328 and was better than the standard drug. Among all the synthesized compounds, only nine compounds (2d, 2g, 2h, 3d, 4a, 4b, 4c, 4d and 4e) exhibited potent anti-inflammatory and analgesic activities with significantly reduced gastrointestinal toxicity in various animal models in comparison to standard drug, diclofenac. Therefore, it is recommended to explore the potential of the synthesized compounds as lead candidates for the development of new therapeutic agents.

  19. Biological therapeutics

    National Research Council Canada - National Science Library

    Greenstein, Ben; Brook, Daniel A

    2011-01-01

    This introductory textbook covers all the main categories of biological medicines, including vaccines, hormonal preparations, drugs for rheumatoid arthritis and other connective tissue diseases, drugs...

  20. 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.

  1. Computational biology

    DEFF Research Database (Denmark)

    Hartmann, Lars Røeboe; Jones, Neil; Simonsen, Jakob Grue

    2011-01-01

    Computation via biological devices has been the subject of close scrutiny since von Neumann’s early work some 60 years ago. In spite of the many relevant works in this field, the notion of programming biological devices seems to be, at best, ill-defined. While many devices are claimed or proved t...

  2. Mesoscopic biology

    Indian Academy of Sciences (India)

    In this paper we present a qualitative outlook of mesoscopic biology where the typical length scale is of the order of nanometers and the energy scales comparable to thermal energy. Novel biomolecular machines, governed by coded information at the level of DNA and proteins, operate at these length scales in biological ...

  3. 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.

  4. A Western Blot-based Investigation of the Yeast Secretory Pathway Designed for an Intermediate-Level Undergraduate Cell Biology Laboratory

    Science.gov (United States)

    Hood-DeGrenier, Jennifer K.

    2008-01-01

    The movement of newly synthesized proteins through the endomembrane system of eukaryotic cells, often referred to generally as the secretory pathway, is a topic covered in most intermediate-level undergraduate cell biology courses. An article previously published in this journal described a laboratory exercise in which yeast mutants defective in…

  5. Design of Indium Arsenide nanowire sensors for pH and biological sensing and low temperature transport through p-doped Indium Arsenide nanowires

    DEFF Research Database (Denmark)

    Upadhyay, Shivendra

    With the goal of real time electrical detection of chemical and biological species, nanowires have shown great promise with high sensitivity due to their large surface to volume ratio. While the focus of such electrical detection has shifted to one dimensional semiconductor nanostuctures, Silicon...

  6. Different design of enzyme-triggered CO-releasing molecules (ET-CORMs) reveals quantitative differences in biological activities in terms of toxicity and inflammation

    NARCIS (Netherlands)

    Stamellou, E.; Storz, D.; Botov, S.; Ntasis, E.; Wedel, J.; Sollazzo, S.; Kraemer, B. K.; van Son, W.; Seelen, M.; Schmalz, H. G.; Schmidt, A.; Hafner, M.; Yard, B. A.

    2014-01-01

    Acyloxydiene-Fe(CO)(3) complexes can act as enzyme-triggered CO-releasing molecules (ET-CORMs). Their biological activity strongly depends on the mother compound from which they are derived, i.e, cyclohexenone or cyclohexanedione, and on the position of the ester functionality they harbour. The

  7. Quantum Biology

    Directory of Open Access Journals (Sweden)

    Alessandro Sergi

    2009-06-01

    Full Text Available A critical assessment of the recent developmentsof molecular biology is presented.The thesis that they do not lead to a conceptualunderstanding of life and biological systems is defended.Maturana and Varela's concept of autopoiesis is briefly sketchedand its logical circularity avoided by postulatingthe existence of underlying living processes,entailing amplification from the microscopic to the macroscopic scale,with increasing complexity in the passage from one scale to the other.Following such a line of thought, the currently accepted model of condensed matter, which is based on electrostatics and short-ranged forces,is criticized. It is suggested that the correct interpretationof quantum dispersion forces (van der Waals, hydrogen bonding, and so onas quantum coherence effects hints at the necessity of includinglong-ranged forces (or mechanisms for them incondensed matter theories of biological processes.Some quantum effects in biology are reviewedand quantum mechanics is acknowledged as conceptually important to biology since withoutit most (if not all of the biological structuresand signalling processes would not even exist. Moreover, it is suggested that long-rangequantum coherent dynamics, including electron polarization,may be invoked to explain signal amplificationprocess in biological systems in general.

  8. Biological desulfurisation

    Energy Technology Data Exchange (ETDEWEB)

    Arena, B.J. [UOP LLC (United States); Benschop, A.; Janssen, A. [Paques Natural Solutions (Netherlands); Kijlstra, S. [Shell Global Solutions (Netherlands)

    2001-03-01

    This article focuses on the biological THIOPAQ process for removing hydrogen sulphide from refinery gases and recovering elemental sulphur. Details are given of the process which absorbs hydrogen sulphide-containing gas in alkaline solution prior to oxidation of the dissolved sulphur to elemental sulphur in a THIOPAQ aerobic biological reactor, with regeneration of the caustic solution. Sulphur handling options including sulphur wash, the drying of the sulphur cake, and sulphur smelting by pressure liquefaction are described. Agricultural applications of the biologically recovered sulphur, and application of the THIOPAQ process to sulphur recovery are discussed.

  9. Using student motivation to design groups in a non-majors biology course for team-based collaborative learning: Impacts on knowledge, views, attitudes, and perceptions

    Science.gov (United States)

    Walters, Kristi L.

    The importance of student motivation and its connection to other learning variables (i.e., attitudes, knowledge, persistence, attendance) is well established. Collaborative work at the undergraduate level has been recognized as a valuable tool in large courses. However, motivation and collaborative group work have rarely been combined. This project utilized student motivation to learn biology to place non-major biology undergraduates in collaborative learning groups at East Carolina University, a mid-sized southeastern American university, to determine the effects of this construct on student learning. A pre-test measuring motivation to learn biology, attitudes toward biology, perceptions of biology and biologists, views of science, and content knowledge was administered. A similar post-test followed as part of the final exam. Two sections of the same introductory biology course (n = 312) were used and students were divided into homogeneous and heterogeneous groups (based on their motivation score). The heterogeneous groups (n = 32) consisted of a mixture of different motivation levels, while the homogeneous groups (n = 32) were organized into teams with similar motivation scores using tiers of high-, middle-, and low-level participants. Data analysis determined mixed perceptions of biology and biologists. These include the perceptions biology was less intriguing, less relevant, less practical, less ethical, and less understandable. Biologists were perceived as being neat and slightly intelligent, but not very altruistic, humane, ethical, logical, honest, or moral. Content knowledge scores more than doubled from pre- to post-test. Half of the items measuring views of science were not statistically significantly different from pre- to post-test. Many of the factors for attitudes toward biology became more agreeable from pre- to post-test. Correlations between motivation scores, participation levels, attendance rates, and final course grades were examined at both the

  10. Systems Biology

    Indian Academy of Sciences (India)

    IAS Admin

    study and understand the function of biological systems, particu- larly, the response of such .... understand the organisation and behaviour of prokaryotic sys- tems. ... relationship of the structure of a target molecule to its ability to bind a certain ...

  11. A Simple and Reliable Method of Design for Standalone Photovoltaic Systems

    Science.gov (United States)

    Srinivasarao, Mantri; Sudha, K. Rama; Bhanu, C. V. K.

    2017-06-01

    Standalone photovoltaic (SAPV) systems are seen as a promoting method of electrifying areas of developing world that lack power grid infrastructure. Proliferations of these systems require a design procedure that is simple, reliable and exhibit good performance over its life time. The proposed methodology uses simple empirical formulae and easily available parameters to design SAPV systems, that is, array size with energy storage. After arriving at the different array size (area), performance curves are obtained for optimal design of SAPV system with high amount of reliability in terms of autonomy at a specified value of loss of load probability (LOLP). Based on the array to load ratio (ALR) and levelized energy cost (LEC) through life cycle cost (LCC) analysis, it is shown that the proposed methodology gives better performance, requires simple data and is more reliable when compared with conventional design using monthly average daily load and insolation.

  12. [Biological agents].

    Science.gov (United States)

    Amano, Koichi

    2009-03-01

    There are two types of biological agents for the treatment of rheumatoid arthritis (RA); monoclonal antibodies and recombinant proteins. Among the latter, etanercept, a recombinant fusion protein of soluble TNF receptor and IgG was approved in 2005 in Japan. The post-marketing surveillance of 13,894 RA patients revealed the efficacy and safety profiles of etanercept in the Japanese population, as well as overseas studies. Abatacept, a recombinant fusion protein of CTLA4 and IgG, is another biological agent for RA. Two clinical trials disclosed the efficacy of abatacept for difficult-to-treat patients: the AIM for MTX-resistant cases and the ATTAIN for patients who are resistant to anti-TNF. The ATTEST trial suggested abatacept might have more acceptable safety profile than infliximab. These biologics are also promising for the treatment of RA for not only relieving clinical symptoms and signs but retarding structural damage.

  13. Biological preconcentrator

    Science.gov (United States)

    Manginell, Ronald P [Albuquerque, NM; Bunker, Bruce C [Albuquerque, NM; Huber, Dale L [Albuquerque, NM

    2008-09-09

    A biological preconcentrator comprises a stimulus-responsive active film on a stimulus-producing microfabricated platform. The active film can comprise a thermally switchable polymer film that can be used to selectively absorb and desorb proteins from a protein mixture. The biological microfabricated platform can comprise a thin membrane suspended on a substrate with an integral resistive heater and/or thermoelectric cooler for thermal switching of the active polymer film disposed on the membrane. The active polymer film can comprise hydrogel-like polymers, such as poly(ethylene oxide) or poly(n-isopropylacrylamide), that are tethered to the membrane. The biological preconcentrator can be fabricated with semiconductor materials and technologies.

  14. Microgravity Fluids for Biology, Workshop

    Science.gov (United States)

    Griffin, DeVon; Kohl, Fred; Massa, Gioia D.; Motil, Brian; Parsons-Wingerter, Patricia; Quincy, Charles; Sato, Kevin; Singh, Bhim; Smith, Jeffrey D.; Wheeler, Raymond M.

    2013-01-01

    Microgravity Fluids for Biology represents an intersection of biology and fluid physics that present exciting research challenges to the Space Life and Physical Sciences Division. Solving and managing the transport processes and fluid mechanics in physiological and biological systems and processes are essential for future space exploration and colonization of space by humans. Adequate understanding of the underlying fluid physics and transport mechanisms will provide new, necessary insights and technologies for analyzing and designing biological systems critical to NASAs mission. To enable this mission, the fluid physics discipline needs to work to enhance the understanding of the influence of gravity on the scales and types of fluids (i.e., non-Newtonian) important to biology and life sciences. In turn, biomimetic, bio-inspired and synthetic biology applications based on physiology and biology can enrich the fluid mechanics and transport phenomena capabilities of the microgravity fluid physics community.

  15. Multiplexed Engineering in Biology.

    Science.gov (United States)

    Rogers, Jameson K; Church, George M

    2016-03-01

    Biotechnology is the manufacturing technology of the future. However, engineering biology is complex, and many possible genetic designs must be evaluated to find cells that produce high levels of a desired drug or chemical. Recent advances have enabled the design and construction of billions of genetic variants per day, but evaluation capacity remains limited to thousands of variants per day. Here we evaluate biological engineering through the lens of the design–build–test cycle framework and highlight the role that multiplexing has had in transforming the design and build steps. We describe a multiplexed solution to the ‘test’ step that is enabled by new research. Achieving a multiplexed test step will permit a fully multiplexed engineering cycle and boost the throughput of biobased product development by up to a millionfold.

  16. The Ethics of Synthetic Biology

    DEFF Research Database (Denmark)

    Christiansen, Andreas

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

  17. Environmental biology

    International Nuclear Information System (INIS)

    Tschumi, P.A.

    1981-01-01

    Environmental biology illustrates the functioning of ecosystems and the dynamics of populations with many examples from limnology and terrestrial ecology. On this basis, present environmental problems are analyzed. The present environmental crisis is seen as a result of the failure to observe ecological laws. (orig.) [de

  18. Biological timekeeping

    DEFF Research Database (Denmark)

    Lloyd, David

    2016-01-01

    , the networks that connect differenttime domains and the oscillations, rhythms and biological clocks that coordinate andsynchronise the complexity of the living state.“It is the pattern maintained by this homeostasis, which is the touchstone ofour personal identity. Our tissues change as we live: the food we...

  19. Scaffolded biology.

    Science.gov (United States)

    Minelli, Alessandro

    2016-09-01

    Descriptions and interpretations of the natural world are dominated by dichotomies such as organism vs. environment, nature vs. nurture, genetic vs. epigenetic, but in the last couple of decades strong dissatisfaction with those partitions has been repeatedly voiced and a number of alternative perspectives have been suggested, from perspectives such as Dawkins' extended phenotype, Turner's extended organism, Oyama's Developmental Systems Theory and Odling-Smee's niche construction theory. Last in time is the description of biological phenomena in terms of hybrids between an organism (scaffolded system) and a living or non-living scaffold, forming unit systems to study processes such as reproduction and development. As scaffold, eventually, we can define any resource used by the biological system, especially in development and reproduction, without incorporating it as happens in the case of resources fueling metabolism. Addressing biological systems as functionally scaffolded systems may help pointing to functional relationships that can impart temporal marking to the developmental process and thus explain its irreversibility; revisiting the boundary between development and metabolism and also regeneration phenomena, by suggesting a conceptual framework within which to investigate phenomena of regular hypermorphic regeneration such as characteristic of deer antlers; fixing a periodization of development in terms of the times at which a scaffolding relationship begins or is terminated; and promoting plant galls to legitimate study objects of developmental biology.

  20. Biological digestion

    International Nuclear Information System (INIS)

    Rosevear, A.

    1988-01-01

    This paper discusses the biological degradation of non-radioactive organic material occurring in radioactive wastes. The biochemical steps are often performed using microbes or isolated enzymes in combination with chemical steps and the aim is to oxidise the carbon, hydrogen, nitrogen and sulphur to their respective oxides. (U.K.)

  1. Marine Biology

    Science.gov (United States)

    Dewees, Christopher M.; Hooper, Jon K.

    1976-01-01

    A variety of informational material for a course in marine biology or oceanology at the secondary level is presented. Among the topics discussed are: food webs and pyramids, planktonic blooms, marine life, plankton nets, food chains, phytoplankton, zooplankton, larval plankton and filter feeders. (BT)

  2. 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.

  3. 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

  4. Combining supramolecular chemistry with biology

    NARCIS (Netherlands)

    Uhlenheuer, D.A.; Petkau - Milroy, K.; Brunsveld, L.

    2010-01-01

    Supramolecular chemistry has primarily found its inspiration in biological molecules, such as proteins and lipids, and their interactions. Currently the supramolecular assembly of designed compounds can be controlled to great extent. This provides the opportunity to combine these synthetic

  5. Rationale and Design of Family-Based Approach in a Minority Community Integrating Systems-Biology for Promotion of Health (FAMILIA).

    Science.gov (United States)

    Bansilal, Sameer; Vedanthan, Rajesh; Kovacic, Jason C; Soto, Ana Victoria; Latina, Jacqueline; Björkegren, Johan L M; Jaslow, Risa; Santana, Maribel; Sartori, Samantha; Giannarelli, Chiara; Mani, Venkatesh; Hajjar, Roger; Schadt, Eric; Kasarskis, Andrew; Fayad, Zahi A; Fuster, Valentin

    2017-05-01

    The 2020 American Heart Association Impact Goal aims to improve cardiovascular health of all Americans by 20% while reducing deaths from cardiovascular disease and stroke by 20%. A large step toward this goal would be to better understand and take advantage of the significant intersection between behavior and biology across the entire life-span. In the proposed FAMILIA studies, we aim to directly address this major knowledge and clinical health gap by implementing an integrated family-centric health promotion intervention and focusing on the intersection of environment and behavior, while understanding the genetic and biologic basis of cardiovascular disease. We plan to recruit 600 preschool children and their 600 parents or caregivers from 12-15 Head Start schools in Harlem, NY, and perform a 2:1 (2 intervention/1 control) cluster randomization of the schools. The preschool children will receive our intensive 37-hour educational program as the intervention for 4 months. For the adults, those in the "intervention" group will be randomly assigned to 1 of 2 intervention programs: an "individual-focused" or "peer-to-peer based." The primary outcome in children will be a composite score of knowledge (K), attitudes (A), habits (H), related to body mass index Z score (B), exercise (E), and alimentation (A) (KAH-BEA), using questionnaires and anthropometric measurements. For adults, the primary outcome will be a composite score for behaviors/outcomes related to blood pressure, exercise, weight, alimentation (diet) and tobacco (smoking; Fuster-BEWAT score). Saliva will be collected from the children for SNP genotyping, and blood will be collected from adults for RNA sequencing to identify network models and predictors of primary prevention outcomes. The FAMILIA studies seek to demonstrate that targeting a younger age group (3-5 years) and using a family-based approach may be a critical strategy in promoting cardiovascular health across the life-span. Copyright © 2017

  6. Design, synthesis, and biological evaluation of enantiomeric beta-N-acetylhexosaminidase inhibitors LABNAc and DABNAc as potential agents against Tay-Sachs and Sandhoff disease.

    Science.gov (United States)

    Rountree, J S Shane; Butters, Terry D; Wormald, Mark R; Boomkamp, Stephanie D; Dwek, Raymond A; Asano, Naoki; Ikeda, Kyoko; Evinson, Emma L; Nash, Robert J; Fleet, George W J

    2009-03-01

    N-Acetylhexosaminidases are of considerable importance in mammals and are involved in various significant biological processes. In humans, deficiencies of these enzymes in the lysosome, resulting from inherited genetic defects, cause the glycolipid storage disorders Tay-Sachs and Sandhoff diseases. One promising therapy for these diseases involves the use of beta-N-acetylhexosaminidase inhibitors as chemical chaperones to enhance the enzyme activity above sub-critical levels. Herein we describe the synthesis and biological evaluation of a potent inhibitor, 2-acetamido-1,4-imino-1,2,4-trideoxy-L-arabinitol (LABNAc), in a high-yielding 11-step procedure from D-lyxonolactone. The N-benzyl and N-butyl analogues were also prepared and found to be potent inhibitors. The enantiomers DABNAc and NBn-DABNAc were synthesised from L-lyxonolactone, and were also evaluated. The L-iminosugar LABNAc and its derivatives were found to be potent noncompetitive inhibitors of some beta-N-acetylhexosaminidases, while the D-iminosugar DABNAc and its derivatives were found to be weaker competitive inhibitors. These results support previous work postulating that D-iminosugar mimics inhibit D-glycohydrolases competitively, and that their corresponding L-enantiomers show noncompetitive inhibition of these enzymes. Molecular modelling studies confirm that the spatial organisation in enantiomeric inhibitors leads to a different overlay with the monosaccharide substrate. Initial cell-based studies suggest that NBn-LABNAc can act as a chemical chaperone to enhance the deficient enzyme's activity to levels that may cause a positive pharmacological effect. LABNAc, NBn-LABNAc, and NBu-LABNAc are potent and selective inhibitors of beta-N-acetylhexosaminidase and may be useful as therapeutic agents for treating adult Tay-Sachs and Sandhoff diseases.

  7. Optimal Conventional and Semi-Natural Treatments for the Upper Yakima Spring Chinook Salmon Supplementation Project, Treatment Definitions and Descriptions, and Biological Specifications for Facility Design, Final Report 1999

    International Nuclear Information System (INIS)

    Hager, Robert C.; Costello, Ronald J.

    1999-01-01

    This report describes the Yakima Fisheries Project facilities (Cle Elum Hatchery and acclimation satellites) which provide the mechanism to conduct state-of-the-art research for addressing questions about spring chinook supplementation strategies. The definition, descriptions, and specifications for the Yakima spring chinook supplementation program permit evaluation of alternative fish culture techniques that should yield improved methods and procedures to produce wild-like fish with higher survival that can be used to rebuild depleted spring chinook stocks of the Columbia River Basin. The definition and description of three experimental treatments, Optimal Conventional (OCT), Semi-Natural (SNT), Limited Semi-Natural (LSNT), and the biological specifications for facilities have been completed for the upper Yakima spring chinook salmon stock of the Yakima Fisheries Project. The task was performed by the Biological Specifications Work Group (BSWG) represented by Yakama Indian Nation, Washington Department of Fish and Wildlife, National Marine Fisheries Service, and Bonneville Power Administration. The control and experimental variables of the experimental treatments (OCT, SNT, and LSNT) are described in sufficient detail to assure that the fish culture facilities will be designed and operated as a production scale laboratory to produce and test supplemented upper Yakima spring chinook salmon. Product specifications of the treatment groups are proposed to serve as the generic templates for developing greater specificity for measurements of product attributes. These product specifications will be used to monitor and evaluate treatment effects, with respect to the biological response variables (post release survival, long-term fitness, reproductive success and ecological interactions)

  8. Optimal Conventional and Semi-Natural Treatments for the Upper Yakima Spring Chinook Salmon Supplementation Project; Treatment Definitions and Descriptions and Biological Specifications for Facility Design, 1995-1999 Final Report.

    Energy Technology Data Exchange (ETDEWEB)

    Hager, Robert C. (Hatchery Operations Consulting); Costello, Ronald J. (Mobrand Biometrics, Inc., Vashon Island, WA)

    1999-10-01

    This report describes the Yakima Fisheries Project facilities (Cle Elum Hatchery and acclimation satellites) which provide the mechanism to conduct state-of-the-art research for addressing questions about spring chinook supplementation strategies. The definition, descriptions, and specifications for the Yakima spring chinook supplementation program permit evaluation of alternative fish culture techniques that should yield improved methods and procedures to produce wild-like fish with higher survival that can be used to rebuild depleted spring chinook stocks of the Columbia River Basin. The definition and description of three experimental treatments, Optimal Conventional (OCT), Semi-Natural (SNT), Limited Semi-Natural (LSNT), and the biological specifications for facilities have been completed for the upper Yakima spring chinook salmon stock of the Yakima Fisheries Project. The task was performed by the Biological Specifications Work Group (BSWG) represented by Yakama Indian Nation, Washington Department of Fish and Wildlife, National Marine Fisheries Service, and Bonneville Power Administration. The control and experimental variables of the experimental treatments (OCT, SNT, and LSNT) are described in sufficient detail to assure that the fish culture facilities will be designed and operated as a production scale laboratory to produce and test supplemented upper Yakima spring chinook salmon. Product specifications of the treatment groups are proposed to serve as the generic templates for developing greater specificity for measurements of product attributes. These product specifications will be used to monitor and evaluate treatment effects, with respect to the biological response variables (post release survival, long-term fitness, reproductive success and ecological interactions).

  9. Understanding Biological Regulation Through Synthetic Biology.

    Science.gov (United States)

    Bashor, Caleb J; Collins, James J

    2018-03-16

    Engineering synthetic gene regulatory circuits proceeds through iterative cycles of design, building, and testing. Initial circuit designs must rely on often-incomplete models of regulation established by fields of reductive inquiry-biochemistry and molecular and systems biology. As differences in designed and experimentally observed circuit behavior are inevitably encountered, investigated, and resolved, each turn of the engineering cycle can force a resynthesis in understanding of natural network function. Here, we outline research that uses the process of gene circuit engineering to advance biological discovery. Synthetic gene circuit engineering research has not only refined our understanding of cellular regulation but furnished biologists with a toolkit that can be directed at natural systems to exact precision manipulation of network structure. As we discuss, using circuit engineering to predictively reorganize, rewire, and reconstruct cellular regulation serves as the ultimate means of testing and understanding how cellular phenotype emerges from systems-level network function. Expected final online publication date for the Annual Review of Biophysics Volume 47 is May 20, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

  10. Biological Soft Robotics.

    Science.gov (United States)

    Feinberg, Adam W

    2015-01-01

    In nature, nanometer-scale molecular motors are used to generate force within cells for diverse processes from transcription and transport to muscle contraction. This adaptability and scalability across wide temporal, spatial, and force regimes have spurred the development of biological soft robotic systems that seek to mimic and extend these capabilities. This review describes how molecular motors are hierarchically organized into larger-scale structures in order to provide a basic understanding of how these systems work in nature and the complexity and functionality we hope to replicate in biological soft robotics. These span the subcellular scale to macroscale, and this article focuses on the integration of biological components with synthetic materials, coupled with bioinspired robotic design. Key examples include nanoscale molecular motor-powered actuators, microscale bacteria-controlled devices, and macroscale muscle-powered robots that grasp, walk, and swim. Finally, the current challenges and future opportunities in the field are addressed.

  11. Biological flue gas desulfurization

    Energy Technology Data Exchange (ETDEWEB)

    Buisman, C.J.N.; Dijkman, H.; Wijte, G.; Prins, W.L.; Verbraak, P.; Hartog, H.A.J. den [Paper B.V. Blak (Netherlands)

    1995-08-01

    A new biological flue gas desulfurization process (BIO-FGD) producing sulphur as a by-product was invented by Paques BV and Hoogens Technical Services in 1993. Sulphur dioxide is absorbed from flue gas using a combination of a sodium based scrubber and two biological reactors, an anaerobic and an aerobic biological reactor. The article describes the process and its evaluation in a pilot plant at 2 MW scale, designed to remove 6 kg/hr SO{sub 2} of the 2 million m{sup 3}/hr of flue gas produced at the 600 MW coal fired power station Amer-8 situated in Geertruidenberg in the south of the Netherlands. Research so far has proved the process works successfully and at low cost. A second pilot plant due to start-up in May 1995 will provide data on scale up and further information on sulphur recovery. 5 refs., 5 figs.

  12. Full scale experimental assessment of reliability of steady state design criteria of activated sludge process with biological nitrogen removal and chemical phosphorus removal; Verifica sperimentale a scala reale di criteri di dimensionamento dei sistemi a fanghi attivi per la rimozione dei nutrienti

    Energy Technology Data Exchange (ETDEWEB)

    Tatano, F. [Politecnico di Milano, Milan (Italy). Dip. di Ingegneria Idraulica, Ambientale e del Rilevamento, Sez. Ambientale

    1996-06-01

    The biological phase of a wastewater treatment plant situated in the Ruhr River Region (Germany), has been monitored for about one year. The collected experimental data have been elaborated in this paper with the objective of an assessment of the reliability of some recent steady-state design criteria of the activated sludge process with biological nitrogen removal and chemical phosphorus removal.

  13. Biological radioprotector

    International Nuclear Information System (INIS)

    Stefanescu, Ioan; Titescu, Gheorghe; Tamaian, Radu; Haulica, Ion; Bild, Walther

    2002-01-01

    According to the patent description, the biological radioprotector is deuterium depleted water, DDW, produced by vacuum distillation with an isotopic content lower than natural value. It appears as such or in a mixture with natural water and carbon dioxide. It can be used for preventing and reducing the ionizing radiation effects upon humans or animal organisms, exposed therapeutically, professionally or accidentally to radiation. The most significant advantage of using DDW as biological radioprotector results from its way of administration. Indeed no one of the radioprotectors currently used today can be orally administrated, what reduces the patients' compliance to prophylactic administrations. The biological radioprotector is an unnoxious product obtained from natural water, which can be administrated as food additive instead of drinking water. Dose modification factor is according to initial estimates around 1.9, what is a remarkable feature when one takes into account that the product is toxicity-free and side effect-free and can be administrated prophylactically as a food additive. A net radioprotective action of the deuterium depletion was evidenced experimentally in laboratory animals (rats) hydrated with DDW of 30 ppm D/(D+H) concentration as compared with normally hydrated control animals. Knowing the effects of irradiation and mechanisms of the acute radiation disease as well as the effects of administration of radiomimetic chemicals upon cellular lines of fast cell division, it appears that the effects of administrating DDW result from stimulation of the immunity system. In conclusion, the biological radioprotector DDW presents the following advantages: - it is obtained from natural products without toxicity; - it is easy to be administrated as a food additive, replacing the drinking water; - besides radioprotective effects, the product has also immunostimulative and antitumoral effects

  14. Marine biology

    International Nuclear Information System (INIS)

    Thurman, H.V.; Webber, H.H.

    1984-01-01

    This book discusses both taxonomic and ecological topics on marine biology. Full coverage of marine organisms of all five kingdoms is provided, along with interesting and thorough discussion of all major marine habitats. Organization into six major parts allows flexibility. It also provides insight into important topics such as disposal of nuclear waste at sea, the idea that life began on the ocean floor, and how whales, krill, and people interact. A full-color photo chapter reviews questions, and exercises. The contents are: an overview marine biology: fundamental concepts/investigating life in the ocean; the physical ocean, the ocean floor, the nature of water, the nature and motion of ocean water; general ecology, conditions for life in the sea, biological productivity and energy transfer; marine organisms; monera, protista, mycota and metaphyta; the smaller marine animals, the large animals marine habitats, the intertidal zone/benthos of the continental shelf, the photic zone, the deep ocean, the ocean under stress, marine pollution, appendix a: the metric system and conversion factors/ appendix b: prefixes and suffixes/ appendix c: taxonomic classification of common marine organisms, and glossary, and index

  15. Synthetic biology: engineering molecular computers

    CERN Multimedia

    CERN. Geneva

    2018-01-01

    Complicated systems cannot survive the rigors of a chaotic environment, without balancing mechanisms that sense, decide upon and counteract the exerted disturbances. Especially so with living organisms, forced by competition to incredible complexities, escalating also their self-controlling plight. Therefore, they compute. Can we harness biological mechanisms to create artificial computing systems? Biology offers several levels of design abstraction: molecular machines, cells, organisms... ranging from the more easily-defined to the more inherently complex. At the bottom of this stack we find the nucleic acids, RNA and DNA, with their digital structure and relatively precise interactions. They are central enablers of designing artificial biological systems, in the confluence of engineering and biology, that we call Synthetic biology. In the first part, let us follow their trail towards an overview of building computing machines with molecules -- and in the second part, take the case study of iGEM Greece 201...

  16. Metal based biologically active compounds: Design, synthesis, DNA binding and antidiabetic activity of 6-methyl-3-formyl chromone derived hydrazones and their metal (II) complexes.

    Science.gov (United States)

    Philip, Jessica Elizabeth; Shahid, Muhammad; Prathapachandra Kurup, M R; Velayudhan, Mohanan Puzhavoorparambil

    2017-10-01

    Two chromone hydrazone ligands HL 1 and HL 2 were synthesized and characterized by elemental analyses, IR, 1 H NMR & 13 C NMR, electronic absorption and mass spectra. The reactions of the chromone hydrazones with transition metals such as Ni, Cu, and Zn (II) salts of acetate afforded mononuclear metal complexes. Characterization and structure elucidation of the prepared chromone hydrazone metal (II) complexes were done by elemental, IR, electronic, EPR spectra and thermo gravimetric analyses as well as conductivity and magnetic susceptibility measurements. The spectroscopic data showed that the ligand acts as a mono basic bidentate with coordination sites are azomethine nitrogen and hydrazonic oxygen, and they exhibited distorted geometry. The biological studies involved antidiabetic activity i.e. enzyme inhibition of α-amylase and α-glucosidase, Calf Thymus - DNA (CT-DNA) interaction and molecular docking. Potential capacity of synthesized compounds to inhibit the α-amylase and α-glucosidase activity was assayed whereas DNA interaction studies were carried out with the help UV-Vis absorption titration and viscosity method. The docking studies of chromone hydrazones show that they are minor groove binders. Complexes were found to be good DNA - intercalates. Chromone hydrazones and its transition metal complexes have shown comparable antidiabetic activity with a standard drug acarbose. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Elucidation of the role of biological factors and device design in cerebral NIRS using an in vivo hematoma model based on high-intensity focused ultrasound

    Science.gov (United States)

    Wang, Jianting; Huang, Stanley; Myers, Matthew; Chen, Yu; Welle, Cristin; Pfefer, Joshua

    2016-03-01

    Near-Infrared Spectroscopy (NIRS) is an emerging medical countermeasure for rapid, field detection of hematomas caused by traumatic brain injury (TBI). Bench and animal tests to determine NIRS sensitivity and specificity are needed. However, current animal models involving non-invasively induced, localized neural damage are limited. We investigated an in vivo murine hematoma model in which cerebral hemorrhage was induced noninvasively by high-intensity focused ultrasound (HIFU) with calibrated positioning and parameters. To characterize the morphology of induced hematomas, we used skull-intact histological evaluation. A multi-wavelength fiber-optic NIRS system with three source-detector separation distances was used to detect hematoma A 1.1 MHz transducer produced consistent small-to-medium hematoma localized to a single hemisphere, along with bruising of the scalp, with a low mortality rate. A 220 kHz transducer produced larger, more diffuse hematomas, with higher variability in size and a correspondingly higher mortality rate. No skin bruising or blood accumulation between the skin and skull was observed following injury application with the 220 kHz transducer. Histological analysis showed higher sensitivity for larger hematomas (>4x4 mm2). NIRS optical density change after HIFU was able to detect all hematomas, with sensitivity dependent on wavelength and separation distance. While improvements in methods for validating cerebral blood distribution are needed, the HIFU hematoma model provided useful insights that will inform development of biologically relevant, performance test methods for cerebral NIRS systems.

  18. Structural Biology Fact Sheet

    Science.gov (United States)

    ... NIGMS NIGMS Home > Science Education > Structural Biology Structural Biology Tagline (Optional) Middle/Main Content Area PDF Version (688 KB) Other Fact Sheets What is structural biology? Structural biology is the study of how biological ...

  19. Design Space Toolbox V2: Automated Software Enabling a Novel Phenotype-Centric Modeling Strategy for Natural and Synthetic Biological Systems

    Directory of Open Access Journals (Sweden)

    Jason Gunther Lomnitz

    2016-07-01

    Full Text Available Mathematical models of biochemical systems provide a means to elucidate the link between the genotype, environment and phenotype. A subclass of mathematical models, known as mechanistic models, quantitatively describe the complex non-linear mechanisms that capture the intricate interactions between biochemical components. However, the study of mechanistic models is challenging because most are analytically intractable and involve large numbers of system parameters. Conventional methods to analyze them rely on local analyses about a nominal parameter set and they do not reveal the vast majority of potential phenotypes possible for a given system design. We have recently developed a new modeling approach that does not require estimated values for the parameters initially and inverts the typical steps of the conventional modeling strategy. Instead, this approach relies on architectural features of the model to identify the phenotypic repertoire and then predict values for the parameters that yield specific instances of the system that realize desired phenotypic characteristics. Here, we present a collection of software tools, the Design Space Toolbox V2 based on the System Design Space method, that automates (1 enumeration of the repertoire of model phenotypes, (2 prediction of values for the parameters for any model phenotype and (3 analysis of model phenotypes through analytical and numerical methods. The result is an enabling technology that facilitates this radically new, phenotype-centric, modeling approach. We illustrate the power of these new tools by applying them to a synthetic gene circuit that can exhibit multi-stability. We then predict values for the system parameters such that the design exhibits 2, 3 and 4 stable steady states. In one example, inspection of the basins of attraction reveals that the circuit can count between 3 stable states by transient stimulation through one of two input channels: a positive channel that increases

  20. Design Space Toolbox V2: Automated Software Enabling a Novel Phenotype-Centric Modeling Strategy for Natural and Synthetic Biological Systems

    Science.gov (United States)

    Lomnitz, Jason G.; Savageau, Michael A.

    2016-01-01

    Mathematical models of biochemical systems provide a means to elucidate the link between the genotype, environment, and phenotype. A subclass of mathematical models, known as mechanistic models, quantitatively describe the complex non-linear mechanisms that capture the intricate interactions between biochemical components. However, the study of mechanistic models is challenging because most are analytically intractable and involve large numbers of system parameters. Conventional methods to analyze them rely on local analyses about a nominal parameter set and they do not reveal the vast majority of potential phenotypes possible for a given system design. We have recently developed a new modeling approach that does not require estimated values for the parameters initially and inverts the typical steps of the conventional modeling strategy. Instead, this approach relies on architectural features of the model to identify the phenotypic repertoire and then predict values for the parameters that yield specific instances of the system that realize desired phenotypic characteristics. Here, we present a collection of software tools, the Design Space Toolbox V2 based on the System Design Space method, that automates (1) enumeration of the repertoire of model phenotypes, (2) prediction of values for the parameters for any model phenotype, and (3) analysis of model phenotypes through analytical and numerical methods. The result is an enabling technology that facilitates this radically new, phenotype-centric, modeling approach. We illustrate the power of these new tools by applying them to a synthetic gene circuit that can exhibit multi-stability. We then predict values for the system parameters such that the design exhibits 2, 3, and 4 stable steady states. In one example, inspection of the basins of attraction reveals that the circuit can count between three stable states by transient stimulation through one of two input channels: a positive channel that increases the count

  1. Design Space Toolbox V2: Automated Software Enabling a Novel Phenotype-Centric Modeling Strategy for Natural and Synthetic Biological Systems.

    Science.gov (United States)

    Lomnitz, Jason G; Savageau, Michael A

    2016-01-01

    Mathematical models of biochemical systems provide a means to elucidate the link between the genotype, environment, and phenotype. A subclass of mathematical models, known as mechanistic models, quantitatively describe the complex non-linear mechanisms that capture the intricate interactions between biochemical components. However, the study of mechanistic models is challenging because most are analytically intractable and involve large numbers of system parameters. Conventional methods to analyze them rely on local analyses about a nominal parameter set and they do not reveal the vast majority of potential phenotypes possible for a given system design. We have recently developed a new modeling approach that does not require estimated values for the parameters initially and inverts the typical steps of the conventional modeling strategy. Instead, this approach relies on architectural features of the model to identify the phenotypic repertoire and then predict values for the parameters that yield specific instances of the system that realize desired phenotypic characteristics. Here, we present a collection of software tools, the Design Space Toolbox V2 based on the System Design Space method, that automates (1) enumeration of the repertoire of model phenotypes, (2) prediction of values for the parameters for any model phenotype, and (3) analysis of model phenotypes through analytical and numerical methods. The result is an enabling technology that facilitates this radically new, phenotype-centric, modeling approach. We illustrate the power of these new tools by applying them to a synthetic gene circuit that can exhibit multi-stability. We then predict values for the system parameters such that the design exhibits 2, 3, and 4 stable steady states. In one example, inspection of the basins of attraction reveals that the circuit can count between three stable states by transient stimulation through one of two input channels: a positive channel that increases the count

  2. 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.

  3. Synthetic biology and occupational risk.

    Science.gov (United States)

    Howard, John; Murashov, Vladimir; Schulte, Paul

    2017-03-01

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

  4. A systems biology approach to studying Tai Chi, physiological complexity and healthy aging: design and rationale of a pragmatic randomized controlled trial.

    Science.gov (United States)

    Wayne, Peter M; Manor, Brad; Novak, Vera; Costa, Madelena D; Hausdorff, Jeffrey M; Goldberger, Ary L; Ahn, Andrew C; Yeh, Gloria Y; Peng, C-K; Lough, Matthew; Davis, Roger B; Quilty, Mary T; Lipsitz, Lewis A

    2013-01-01

    Aging is typically associated with progressive multi-system impairment that leads to decreased physical and cognitive function and reduced adaptability to stress. Due to its capacity to characterize complex dynamics within and between physiological systems, the emerging field of complex systems biology and its array of quantitative tools show great promise for improving our understanding of aging, monitoring senescence, and providing biomarkers for evaluating novel interventions, including promising mind-body exercises, that treat age-related disease and promote healthy aging. An ongoing, two-arm randomized clinical trial is evaluating the potential of Tai Chi mind-body exercise to attenuate age-related loss of complexity. A total of 60 Tai Chi-naïve healthy older adults (aged 50-79) are being randomized to either six months of Tai Chi training (n=30), or to a waitlist control receiving unaltered usual medical care (n=30). Our primary outcomes are complexity-based measures of heart rate, standing postural sway and gait stride interval dynamics assessed at 3 and 6months. Multiscale entropy and detrended fluctuation analysis are used as entropy- and fractal-based measures of complexity, respectively. Secondary outcomes include measures of physical and psychological function and tests of physiological adaptability also assessed at 3 and 6months. Results of this study may lead to novel biomarkers that help us monitor and understand the physiological processes of aging and explore the potential benefits of Tai Chi and related mind-body exercises for healthy aging. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Novel, energy-optimized membrane design for biological waste water treatment systems; Ein neuentwickeltes Niedrig-Energie-Membransystem fuer Membran-Biologien

    Energy Technology Data Exchange (ETDEWEB)

    Luebbecke, S. [Preussag Wassertechnik GmbH, Bremen (Germany)

    1999-07-01

    In industrial waste water treatment, circular movement of waste water, scarcity of space for erecting waste water treatment plants, and economy are factors of eminent importance, calling for innovative, efficient process techniques. Up to now, separation of activated sludge from cleaned waste water has been done almost exclusively by means of sedimentation. But because of the slight difference in density between water and biomass, large final sedimentation tanks are indispensable, and attainable biomass concentrations in an activated sludge tank (or bioreactor) are low (3-4g/l). Given that cleaning performance is directly proportional to biomass concentration, achieving higher biomass concentrations spells substantially enhanced efficiency per unit of space of biological systems, thus saving reaction volume. For this task, membrane techniques are suitable, which, contrary to sedimentation, permit random-selection, operationally stable retention and concentration of biomass with a definitely smaller space requirement. (orig.) [German] Bei der industriellen Abwasserbehandlung stehen die Kreislauffuehrung des Abwassers, beengte Platzverhaeltnisse fuer die Errichtung von Abwasserbehandlungsanlagen und die Wirtschaftlichkeit im Vordergrund, so dass dort innovative, effiziente Verfahrenstechniken gefragt sind. Zur Abtrennung des Belebtschlammes vom gereinigten Abwasser wird bisher fast ausschliesslich die Sedimentation eingesetzt. Der geringe Dichteunterschied zwischen Wasser und Biomasse macht jedoch grosse Nachklaerbecken notwendig und die erreichbaren Biomassekonzentrationen im Belebungsbecken (bzw. Bioreaktor) sind gering (3-4 g/l). Da die Reinigungsleistung der Biomassekonzentration direkt proportional ist, kann mit der Einstellung hoeherer Biomassekonzentrationen die Raumumsatzleistung biologischer Systeme erheblich gesteigert und somit Reaktionsvolumen eingespart werden. Fuer diese Aufgabe koennen Membranverfahren eingesetzt werden, die im Gegensatz zur

  6. Design, synthesis and biological evaluation of novel ring-opened cromakalim analogues with relaxant effects on vascular and respiratory smooth muscles and as stimulators of elastin synthesis.

    Science.gov (United States)

    Bouhedja, Mourad; Peres, Basile; Fhayli, Wassim; Ghandour, Zeinab; Boumendjel, Ahcène; Faury, Gilles; Khelili, Smail

    2018-01-20

    Two new series of ring-opened analogues of cromakalim bearing sulfonylurea moieties (series A: with N-unmethylated sulfonylureas, series B: with N-methylated sulfonylureas) were synthesized and tested as relaxants of vascular and respiratory smooth muscles (rat aorta and trachea, respectively). Ex vivo biological evaluations indicated that the most active compounds, belonging to series B, displayed a marked vasorelaxant activity on endothelium-intact aortic rings and the trachea. A majority of series B compounds exhibited a higher vasorelaxant activity (EC 50  stronger relaxant effects on the trachea than the reference compound cromakalim (EC 50  = 124 μM), in particular compounds B4, B7 and B16 (EC 50   57 μM for all, and EC 50  > 200 μM for a majority of them), but some of them showed an interesting relaxing effect on trachea (i.e. A15 and A33, EC 50  = 30 μM). The most potent compounds of both series, i.e. A15, A33 and B16, tested on aortic rings in the presence of glibenclamide or 80 mM KCl, suggested that they acted as voltage-gated Ca 2+ channel blockers, like verapamil, instead of being ATP-potassium channel activators, as is cromakalim, the parent molecule. Further investigations on cultured vascular smooth muscle cells showed a strong stimulating effect on elastin synthesis, especially compound B16, which was more active at 20 μM than diazoxide, a reference ATP-sensitive potassium channel activator. Taken together, our results show that the N-methylation of the sulfonylurea moieties of ring-opened cromakalim analogues led to new compounds blocking calcium-gated channels, which had a major impact on the arterial and tracheal activities as well as selectivity. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  7. Safe-by-Design CuO Nanoparticles via Fe-Doping, Cu-O Bond Length Variation, and Biological Assessment in Cells and Zebrafish Embryos.

    Science.gov (United States)

    Naatz, Hendrik; Lin, Sijie; Li, Ruibin; Jiang, Wen; Ji, Zhaoxia; Chang, Chong Hyun; Köser, Jan; Thöming, Jorg; Xia, Tian; Nel, Andre E; Mädler, Lutz; Pokhrel, Suman

    2017-01-24

    The safe implementation of nanotechnology requires nanomaterial hazard assessment in accordance with the material physicochemical properties that trigger the injury response at the nano/bio interface. Since CuO nanoparticles (NPs) are widely used industrially and their dissolution properties play a major role in hazard potential, we hypothesized that tighter bonding of Cu to Fe by particle doping could constitute a safer-by-design approach through decreased dissolution. Accordingly, we designed a combinatorial library in which CuO was doped with 1-10% Fe in a flame spray pyrolysis reactor. The morphology and structural properties were determined by XRD, BET, Raman spectroscopy, HRTEM, EFTEM, and EELS, which demonstrated a significant reduction in the apical Cu-O bond length while simultaneously increasing the planar bond length (Jahn-Teller distortion). Hazard screening was performed in tissue culture cell lines and zebrafish embryos to discern the change in the hazardous effects of doped vs nondoped particles. This demonstrated that with increased levels of doping there was a progressive decrease in cytotoxicity in BEAS-2B and THP-1 cells, as well as an incremental decrease in the rate of hatching interference in zebrafish embryos. The dissolution profiles were determined and the surface reactions taking place in Holtfreter's solution were validated using cyclic voltammetry measurements to demonstrate that the Cu + /Cu 2+ and Fe 2+ /Fe 3+ redox species play a major role in the dissolution process of pure and Fe-doped CuO. Altogether, a safe-by-design strategy was implemented for the toxic CuO particles via Fe doping and has been demonstrated for their safe use in the environment.

  8. Enantioselective Total Synthesis of Antibiotic CJ-16,264, Synthesis and Biological Evaluation of Designed Analogues, and Discovery of Highly Potent and Simpler Antibacterial Agents.

    Science.gov (United States)

    Nicolaou, K C; Pulukuri, Kiran Kumar; Rigol, Stephan; Buchman, Marek; Shah, Akshay A; Cen, Nicholas; McCurry, Megan D; Beabout, Kathryn; Shamoo, Yousif

    2017-11-08

    An improved and enantioselective total synthesis of antibiotic CJ-16,264 through a practical kinetic resolution and an iodolactonization reaction to form the iodo pyrrolizidinone fragment of the molecule is described. A series of racemic and enantiopure analogues of CJ-16,264 was designed and synthesized through the developed synthetic technologies and tested against drug-resistant bacterial strains. These studies led to interesting structure-activity relationships and the identification of a number of simpler, and yet equipotent, or even more potent, antibacterial agents than the natural product, thereby setting the foundation for further investigations in the quest for new anti-infective drugs.

  9. Biology Branch

    Energy Technology Data Exchange (ETDEWEB)

    Baldwin, W F

    1974-12-31

    Progress is reported on the following studies in biochemistry and molecular biology: study of long pyrimidine polynucleotides in DNA; isolation of thymine dimers from Schizosaccharomyces pombe; thermal stability of high molecular weight RNA; nucleases of Micrococcus radiodurans; effect of ionizing radiation on M. radiodurans cell walls and cell membranes; chemical modification of nucleotides; exonucleases of M. radiodurans; and enzymatic basis of repair of radioinduced damage in M. radiodurans. Genetics, development, and population studies include repair pathways and mutation induction in yeast; induction of pure mutant clones in yeast; radiosensitivity of bacteriophage T4; polyacrylamide gel electrophoresis of bacteriophage T4; radiation genetics of Dahibominus; and radiation studies on bitting flies. (HLW)

  10. Novel Tacrine-Benzofuran Hybrids as Potent Multitarget-Directed Ligands for the Treatment of Alzheimer's Disease: Design, Synthesis, Biological Evaluation, and X-ray Crystallography.

    Science.gov (United States)

    Zha, Xiaoming; Lamba, Doriano; Zhang, Lili; Lou, Yinghan; Xu, Changxu; Kang, Di; Chen, Li; Xu, Yungen; Zhang, Luyong; De Simone, Angela; Samez, Sarah; Pesaresi, Alessandro; Stojan, Jure; Lopez, Manuela G; Egea, Javier; Andrisano, Vincenza; Bartolini, Manuela

    2016-01-14

    Twenty-six new tacrine-benzofuran hybrids were designed, synthesized, and evaluated in vitro on key molecular targets for Alzheimer's disease. Most hybrids exhibited good inhibitory activities on cholinesterases and β-amyloid self-aggregation. Selected compounds displayed significant inhibition of human β-secretase-1 (hBACE-1). Among the 26 hybrids, 2e showed the most interesting profile as a subnanomolar selective inhibitor of human acetylcholinesterase (hAChE) (IC50 = 0.86 nM) and a good inhibitor of both β-amyloid aggregation (hAChE- and self-induced, 61.3% and 58.4%, respectively) and hBACE-1 activity (IC50 = 1.35 μM). Kinetic studies showed that 2e acted as a slow, tight-binding, mixed-type inhibitor, while X-ray crystallographic studies highlighted the ability of 2e to induce large-scale structural changes in the active-site gorge of Torpedo californica AChE (TcAChE), with significant implications for structure-based drug design. In vivo studies confirmed that 2e significantly ameliorates performances of scopolamine-treated ICR mice. Finally, 2e administration did not exhibit significant hepatotoxicity.

  11. Biological biomaterials

    Energy Technology Data Exchange (ETDEWEB)

    Jorge-Herrero, E. [Servicio de Cirugia Experimental. Clinica Puerta de Hierro, Madrid (Spain)

    1997-05-01

    There are a number of situations in which substances of biological origin are employed as biomaterials. Most of them are macromolecules derived from isolated connective tissue or the connective tissue itself in membrane form, in both cases, the tissue can be used in its natural form or be chemically treated. In other cases, certain blood vessels can be chemically pretreated and used as vascular prostheses. Proteins such as albumin, collagen and fibrinogen are employed to coat vascular prostheses. Certain polysaccharides have also been tested for use in controlled drug release systems. Likewise, a number of tissues, such as dura mater, bovine pericardium, procine valves and human valves, are used in the preparation of cardiac prostheses. We also use veins from animals or humans in arterial replacement. In none of these cases are the tissues employed dissimilar to the native tissues as they have been chemically modified, becoming a new bio material with different physical and biochemical properties. In short, we find that natural products are being utilized as biomaterials and must be considered as such; thus, it is necessary to study both their chemicobiological and physicomechanical properties. In the present report, we review the current applications, problems and future prospects of some of these biological biomaterials. (Author) 84 refs.

  12. Structure-based drug design, synthesis and biological assays of P. falciparum Atg3-Atg8 protein-protein interaction inhibitors

    Science.gov (United States)

    Villa, Stefania; Legnani, Laura; Colombo, Diego; Gelain, Arianna; Lammi, Carmen; Bongiorno, Daniele; Ilboudo, Denise P.; McGee, Kellen E.; Bosch, Jürgen; Grazioso, Giovanni

    2018-03-01

    The proteins involved in the autophagy (Atg) pathway have recently been considered promising targets for the development of new antimalarial drugs. In particular, inhibitors of the protein-protein interaction (PPI) between Atg3 and Atg8 of Plasmodium falciparum retarded the blood- and liver-stages of parasite growth. In this paper, we used computational techniques to design a new class of peptidomimetics mimicking the Atg3 interaction motif, which were then synthesized by click-chemistry. Surface plasmon resonance has been employed to measure the ability of these compounds to inhibit the Atg3-Atg8 reciprocal protein-protein interaction. Moreover, P. falciparum growth inhibition in red blood cell cultures was evaluated as well as the cyto-toxicity of the compounds.

  13. Design, synthesis, X-ray studies, and biological evaluation of novel macrocyclic HIV-1 protease inhibitors involving the P1'-P2' ligands

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, Arun K.; Sean Fyvie, W.; Brindisi, Margherita; Steffey, Melinda; Agniswamy, Johnson; Wang, Yuan-Fang; Aoki, Manabu; Amano, Masayuki; Weber, Irene T.; Mitsuya, Hiroaki

    2017-11-01

    Design, synthesis, and evaluation of a new class of HIV-1 protease inhibitors containing diverse flexible macrocyclic P1'-P2' tethers are reported. Inhibitor 5a with a pyrrolidinone-derived macrocycle exhibited favorable enzyme inhibitory and antiviral activity (Ki = 13.2 nM, IC50 = 22 nM). Further incorporation of heteroatoms in the macrocyclic skeleton provided macrocyclic inhibitors 5m and 5o. These compounds showed excellent HIV-1 protease inhibitory (Ki = 62 pM and 14 pM, respectively) and antiviral activity (IC50 = 5.3 nM and 2.0 nM, respectively). Inhibitor 5o also remained highly potent against a DRV-resistant HIV-1 variant.

  14. Design, synthesis, and biological activity of 5'-phenyl-1,2,5,6-tetrahydro-3,3'-bipyridine analogues as potential antagonists of nicotinic acetylcholine receptors.

    Science.gov (United States)

    Jin, Yafei; Huang, Xiaoqin; Papke, Roger L; Jutkiewicz, Emily M; Showalter, Hollis D; Zhan, Chang-Guo

    2017-09-15

    Starting from a known non-specific agonist (1) of nicotinic acetylcholine receptors (nAChRs), rationally guided structural-based design resulted in the discovery of a small series of 5'-phenyl-1,2,5,6-tetrahydro-3,3'-bipyridines (3a-3e) incorporating a phenyl ring off the pyridine core of 1. The compounds were synthesized via successive Suzuki couplings on a suitably functionalized pyridine starting monomer 4 to append phenyl and pyridyl substituents off the 3- and 5-positions, respectively, and then subsequent modifications were made on the flanking pyridyl ring to provide target compounds. Compound 3a is a novel antagonist, which is highly selective for α3β4 nAChR (K i =123nM) over the α4β2 and α7 receptors. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Design, Synthesis, and Biological Evaluation of Peptidomimetic N-Substituted Cbz-4-Hyp-Hpa-Amides as Novel Inhibitors of Plasmodium falciparum.

    Science.gov (United States)

    Bacherikov, Valeriy A; Chittiboyina, Amar G; Avery, Mitchell A

    2017-08-01

    A new series of peptidomimetic N-substituted Cbz-4-Hyp-Hpa-amides were designed, synthesized, and evaluated for inhibition of the Plasmodium falciparum. Substituents on the N-atom of the amide group were selected alkyl-, allyl-, aryl-, 2-hydroxyethyl-, 2-cyanoethyl-, cyanomethyl-, 2-hydroxyethyl-, 2,2-diethoxyethyl-, or 2-ethoxy-2-oxoethylamino groups, and about of 40 new compounds were synthesized and evaluated for antiplasmodial activity in vitro. Antimalarial activity has been investigated as for the final peptide mimetics, and their immediate predecessors, carrying TBDMS or TBDPS protecting groups on 4-hydroxyproline residue and 18 derivatives exhibited toxicity against P. falciparum. Of these agents, compound 23e was shown to have potent antimalarial activity with IC 50 528 ng/ml. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

  16. Preliminary design of a biological treatment facility for trench water from a low-level radioactive waste disposal area at West Valley, New York

    Energy Technology Data Exchange (ETDEWEB)

    Rosten, R.; Malkumus, D. [Pacific Nuclear, Inc. (United States); Sonntag, T. [New York State Energy Research and Development Authority, NY (United States); Sundquist, J. [Ecology and Environment, Inc. (United States)

    1993-03-01

    The New York State Energy Research and Development Authority (NYSERDA) owns and manages a State-Licensed Low-Level Radioactive Waste Disposal Area (SDA) at West Valley, New York. Water has migrated into the burial trenches at the SDA and collected there, becoming contaminated with radionuclides and organic compounds. The US Environmental Protection Agency issued an order to NYSERDA to reduce the levels of water in the trenches. A treatability study of the contaminated trench water (leachate) was performed and determined the best available technology to treat the leachate and discharge the effluent. This paper describes the preliminary design of the treatment facility that incorporates the bases developed in the leachate treatability study.

  17. Chapter 5:Biological Properties of Wood

    Science.gov (United States)

    Rebecca E. Ibach

    2013-01-01

    There are numerous biological degradations that wood is exposed to in various environments. Biological damage occurs when a log, sawn product, or final product is not stored, handled, or designed properly. Biological organisms such as bacteria, mold, stain, decay fungi, insects, and marine borers depend heavily on temperature and moisture conditions to grow. Figure 5.1...

  18. Biological effects

    International Nuclear Information System (INIS)

    Trott, K.R.

    1973-01-01

    Following an introduction into the field of cellular radiation effect considering the most important experimental results, the biological significance of the colony formation ability is brought out. The inactivation concept of stem cells does not only prove to be good, according to the present results, in the interpretation of the pathogenesis of acute radiation effects on moult tissue, it also enables chronicle radiation injuries to be interpreted through changes in the fibrous part of the organs. Radiation therapy of tumours can also be explained to a large extent by the radiation effect on the unlimited reproductiveness of tumour cells. The more or less similar dose effect curves for healthy and tumour tissue in practice lead to intermittent irradiation. The dependence of the intermittent doses and intervals on factors such as Elkind recovery, synchronisation, redistribution, reoxygenation, repopulation and regeneration are reviewed. (ORU/LH) [de

  19. Design, synthesis, and biological evaluation of new 1,2,3-triazolo-2'-deoxy-2'-fluoro- 4'-azido nucleoside derivatives as potent anti-HBV agents.

    Science.gov (United States)

    Liu, Yuan; Peng, Youmei; Lu, Jingjing; Wang, Jingwen; Ma, Haoran; Song, Chuanjun; Liu, Bingjie; Qiao, Yan; Yu, Wenquan; Wu, Jie; Chang, Junbiao

    2018-01-01

    Novel drugs are urgently needed to combat hepatitis B virus (HBV) infection due to drug-resistant virus. In this paper, a series of novel 4-monosubstituted 2'-deoxy-2'-β-fluoro-4'-azido-β-d-arabinofuranosyl 1,2,3-triazole nucleoside analogues (1a-g) were designed, synthesized and screened for in vitro anti-HBV activity. At 5.0 μM in the cellular model, all the synthetic compounds display activities comparable to that of the positive control, lamivudine at 20 μM. Of the compounds tested, the amide-substituted analogue (1a) shows the most promising anti-HBV activity and low cytotoxicity in the cell model. In particular, it retains excellent activity against lamivudine-resistant HBV mutants. In duck HBV (DHBV)-infected duck models, both the serum and liver DHBV DNA levels (67.4% and 53.3%, respectively) were reduced markedly by the treatment with 1a. Analysis of the structure of HBV polymer/1a-triphosphate (1a-TP) complex shows that 1a-TP is stabilized by specific van der Waals interactions with the enzyme residues arising from 4-amino-1,2,3-triazole and the 4'-azido group. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  20. Design, synthesis, and biological evaluation of 3-vinyl-quinoxalin-2(1H-one derivatives as novel antitumor inhibitors of FGFR1

    Directory of Open Access Journals (Sweden)

    Liu Z

    2016-05-01

    Full Text Available Zhiguo Liu,1,* Shufang Yu,1,* Di Chen,1 Guoliang Shen,1 Yu Wang,1 Leping Hou,2 Dan Lin,1 Jinsan Zhang,1 Faqing Ye1 1School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 2Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: FGFR1 is well known as a molecular target in anticancer drug design. TKI258 plays an important role in RTK inhibitors. Utilizing TKI258 as a lead compound that contains a quinazolinone nucleus, we synthesized four series of 3-vinyl-quinoxalin-2(1H-one derivatives, a total of 27 compounds. We further evaluated these compounds for FGFR1 inhibition ability as well as cytotoxicity against four cancer cell lines (H460, B16-F10, Hela229, and Hct116 in vitro. Some compounds displayed good-to-excellent potency against the four tested cancer cell lines compared with TKI258. Structure–activity relationship analyses indicated that small substituents at the side chain of the 3-vinyl-quinoxalin-2(1H-one were more effective than large substituents. Lastly, we used molecular docking to obtain further insight into the interactions between the compounds and FGFR1. Keywords: FGFR1, synthesis, quinoxaline, antitumor activity, kinase inhibitor

  1. Design, Synthesis, and Biological Evaluation of Some Novel Pyrrolizine Derivatives as COX Inhibitors with Anti-Inflammatory/Analgesic Activities and Low Ulcerogenic Liability

    Directory of Open Access Journals (Sweden)

    Ahmed M. Gouda

    2016-02-01

    Full Text Available Non-steroidal anti-inflammatory drugs (NSAIDs are the most commonly prescribed anti-inflammatory and pain relief medications. However, their use is associated with many drawbacks, including mainly serious gastric and renal complications. In an attempt to circumvent these risks, a set of N-(4-bromophenyl-7-cyano-6-substituted-H-pyrrolizine-5-carboxamide derivatives were designed, synthesized and evaluated as dual COX/5-LOX inhibitors. The structural elucidation, in vivo anti-inflammatory and analgesic activities using a carrageenan-induced rat paw edema model and hot plate assay, were performed, respectively. From the results obtained, it was found that the newly synthesized pyrrolizines exhibited IC50 values in the range of 2.45–5.69 µM and 0.85–3.44 µM for COX-1 and COX-2, respectively. Interestingly, compounds 12, 13, 16 and 17 showed higher anti-inflammatory and analgesic activities compared to ibuprofen. Among these derivatives, compounds 16 and 19 displayed better safety profile than ibuprofen in acute ulcerogenicity and histopathological studies. Furthermore, the docking studies revealed that compound 17 fits nicely into COX-1 and COX-2 binding sites with the highest binding affinity, while compound 16 exerted the highest binding affinity for 5-LOX. In light of these findings, these novel pyrrolizine-5-carboxamide derivatives represent a promising scaffold for further development into potential dual COX/5-LOX inhibitors with safer gastric profile.

  2. Structure-based design, synthesis, and biological evaluation of novel pyrrolyl aryl sulfones: HIV-1 non-nucleoside reverse transcriptase inhibitors active at nanomolar concentrations.

    Science.gov (United States)

    Artico, M; Silvestri, R; Pagnozzi, E; Bruno, B; Novellino, E; Greco, G; Massa, S; Ettorre, A; Loi, A G; Scintu, F; La Colla, P

    2000-05-04

    Pyrrolyl aryl sulfones (PASs) have been recently reported as a new class of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) inhibitors acting at the non-nucleoside binding site of this enzyme (Artico, M.; et al. J. Med. Chem. 1996, 39, 522-530). Compound 3, the most potent inhibitor within the series (EC(50) = 0.14 microM, IC(50) = 0.4 microM, and SI > 1429), was then selected as a lead compound for a synthetic project based on molecular modeling studies. Using the three-dimensional structure of RT cocrystallized with the alpha-APA derivative R95845, we derived a model of the RT/3 complex by taking into account previously developed structure-activity relationships. Inspection of this model and docking calculations on virtual compounds prompted the design of novel PAS derivatives and related analogues. Our computational approach proved to be effective in making qualitative predictions, that is in discriminating active versus inactive compounds. Among the compounds synthesized and tested, 20 was the most active one, with EC(50) = 0.045 microM, IC(50) = 0.05 microM, and SI = 5333. Compared with the lead 3, these values represent a 3- and 8-fold improvement in the cell-based and enzyme assays, respectively, together with the highest selectivity achieved so far in the PAS series.

  3. Design, synthesis and biological activity of novel donepezil derivatives bearing N-benzyl pyridinium moiety as potent and dual binding site acetylcholinesterase inhibitors.

    Science.gov (United States)

    Lan, Jin-Shuai; Zhang, Tong; Liu, Yun; Yang, Jing; Xie, Sai-Sai; Liu, Jing; Miao, Ze-Yang; Ding, Yue

    2017-06-16

    A series of new donepezil derivatives were designed synthesized and evaluated as multifunctional cholinesterase inhibitors against Alzheimer's disease (AD). In vitro studies showed that most of them exhibited significant potency to inhibit acetylcholinesterase and self-induced β-amyloid (Aβ) aggregation, and moderate antioxidant activity. Especially, compound 5b presented the greatest ability to inhibit cholinesterase (IC 50 , 1.9 nM for eeAChE and 0.8 nM for hAChE), good inhibition of Aβ aggregation (53.7% at 20 μM) and good antioxidant activity (0.54 trolox equivalents). Kinetic and molecular modeling studies indicated that compound 5b was a mixed-type inhibitor, binding simultaneously to the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. In addition, compound 5b could reduce PC12 cells death induced by oxidative stress and Aβ (1-42). Moreover, in vivo experiments showed that compound 5b was nontoxic and tolerated at doses up to 2000 mg/kg. These results suggested that compound 5b might be an excellent multifunctional agent for AD treatment. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. Design, Synthesis, and Biological Evaluation of 2-(Benzylamino-2-HydroxyalkylIsoindoline-1,3-Diones Derivatives as Potential Disease-Modifying Multifunctional Anti-Alzheimer Agents

    Directory of Open Access Journals (Sweden)

    Dawid Panek

    2018-02-01

    Full Text Available The complex nature of Alzheimer’s disease calls for multidirectional treatment. Consequently, the search for multi-target-directed ligands may lead to potential drug candidates. The aim of the present study is to seek multifunctional compounds with expected activity against disease-modifying and symptomatic targets. A series of 15 drug-like various substituted derivatives of 2-(benzylamino-2-hydroxyalkylisoindoline-1,3-diones was designed by modification of cholinesterase inhibitors toward β-secretase inhibition. All target compounds have been synthesized and tested against eel acetylcholinesterase (eeAChE, equine serum butyrylcholinesterase (eqBuChE, human β-secretase (hBACE-1, and β-amyloid (Aβ-aggregation. The most promising compound, 12 (2-(5-(benzylamino-4-hydroxypentylisoindoline-1,3-dione, displayed inhibitory potency against eeAChE (IC50 = 3.33 μM, hBACE-1 (43.7% at 50 μM, and Aβ-aggregation (24.9% at 10 μM. Molecular modeling studies have revealed possible interaction of compound 12 with the active sites of both enzymes—acetylcholinesterase and β-secretase. In conclusion: modifications of acetylcholinesterase inhibitors led to the discovery of a multipotent anti-Alzheimer’s agent, with moderate and balanced potency, capable of inhibiting acetylcholinesterase, a symptomatic target, and disease-modifying targets: β-secretase and Aβ-aggregation.

  5. Design, synthesis and biological evaluation of multifunctional tacrine-curcumin hybrids as new cholinesterase inhibitors with metal ions-chelating and neuroprotective property.

    Science.gov (United States)

    Liu, Zhikun; Fang, Lei; Zhang, Huan; Gou, Shaohua; Chen, Li

    2017-04-15

    Total sixteen tacrine-curcumin hybrid compounds were designed and synthesized for the purpose of searching for multifunctional anti-Alzheimer agents. In vitro studies showed that these hybrid compounds showed good cholinesterase inhibitory activity. Particularly, the potency of K 3-2 is even beyond tacrine. Some of the compounds exhibited different selectivity on acetylcholinesterase or butyrylcholinesterase due to the structural difference. Thus, the structure and activity relationship is summarized and further discussed based on molecular modeling studies. The ORAC and MTT assays indicated that the hybrid compounds possessed pronounced antioxidant activity and could effectively protect PC12 cells from the H 2 O 2 /Aβ42-induced toxicity. Moreover, the hybrid compounds also showed positive metal ions-chelating ability in vitro, suggesting a potential to halt ion-induced Aβ aggregation. All the obtained results demonstrated that the tacrine-curcumin hybrid compounds, in particular compound K 3-2 , can be considered as potential therapeutic agents for Alzheimer's disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Discovery of Novel Bromophenol Hybrids as Potential Anticancer Agents through the Ros-Mediated Apoptotic Pathway: Design, Synthesis and Biological Evaluation

    Directory of Open Access Journals (Sweden)

    Li-Jun Wang

    2017-11-01

    Full Text Available A series of bromophenol hybrids with N-containing heterocyclic moieties were designed, and their anticancer activities against a panel of five human cancer cell lines (A549, Bel7402, HepG2, HCT116 and Caco2 using MTT assay in vitro were explored. Among them, thirteen compounds (17a, 17b, 18a, 19a, 19b, 20a, 20b, 21a, 21b, 22a, 22b, 23a, and 23b exhibited significant inhibitory activity against the tested cancer cell lines. The structure-activity relationships (SARs of bromophenol derivatives were discussed. The promising candidate compound 17a could induce cell cycle arrest at G0/G1 phase and induce apoptosis in A549 cells, as well as caused DNA fragmentations, morphological changes and ROS generation by the mechanism studies. Furthermore, compound 17a suppression of Bcl-2 levels (decrease in the expression of the anti-apoptotic proteins Bcl-2 and down-regulation in the expression levels of Bcl-2 in A549 cells were observed, along with activation caspase-3 and PARP, which indicated that compound 17a induced A549 cells apoptosis in vitro through the ROS-mediated apoptotic pathway. These results might be useful for bromophenol derivatives to be explored and developed as novel anticancer drugs.

  7. Design, optimization, and biological evaluation of novel keto-benzimidazoles as potent and selective inhibitors of phosphodiesterase 10A (PDE10A).

    Science.gov (United States)

    Hu, Essa; Kunz, Roxanne K; Chen, Ning; Rumfelt, Shannon; Siegmund, Aaron; Andrews, Kristin; Chmait, Samer; Zhao, Sharon; Davis, Carl; Chen, Hang; Lester-Zeiner, Dianna; Ma, Ji; Biorn, Christopher; Shi, Jianxia; Porter, Amy; Treanor, James; Allen, Jennifer R

    2013-11-14

    Our development of PDE10A inhibitors began with an HTS screening hit (1) that exhibited both high p-glycoprotein (P-gp) efflux ratios in rat and human and poor metabolic stability. On the basis of cocrystal structure of 1 in human PDE10A enzyme, we designed a novel keto-benzimidazole 26 with comparable PDE10A potency devoid of efflux liabilities. On target in vivo coverage of PDE10A in rat brain was assessed using our previously reported LC-MS/MS receptor occupancy (RO) technology. Compound 26 achieved 55% RO of PDE10A at 30 mg/kg po and covered PDE10A receptors in rat brain in a dose-dependent manner. Cocrystal structure of 26 in PDE10A confirmed the binding mode of the novel scaffold. Further optimization resulted in the identification of keto-benzimidazole 34, which showed an increased in vivo efficacy of 57% RO in rats at 10 mg/kg po and an improved in vivo rat clearance and oral bioavailability.

  8. Cancer stem cells CD133 inhibition and cytotoxicity of certain 3-phenylthiazolo[3,2-a]benzimidazoles: design, direct synthesis, crystal study and in vitro biological evaluation.

    Science.gov (United States)

    Al-Ansary, Ghada H; Eldehna, Wagdy M; Ghabbour, Hazem A; Al-Rashood, Sara T A; Al-Rashood, Khalid A; Eladwy, Radwa A; Al-Dhfyan, Abdullah; Kabil, Maha M; Abdel-Aziz, Hatem A

    2017-12-01

    Cancer stem cells (CSCs) have been objects of intensive study since their identification in 1994. Adopting a structural rigidification approach, a novel series of 3-phenylthiazolo[3,2-a]benzimidazoles 4a-d was designed and synthesised, in an attempt to develop potent anticancer agent that can target the bulk of tumour cells and CSCs. The anti-proliferative activity of the synthesised compounds was evaluated against two cell lines, namely; colon cancer HT-29 and triple negative breast cancer MDA-MB-468 cell lines. Also, their inhibitory activity against the cell surface expression of CD133 was examined. In particular, compound 4b emerged as a promising hit molecule as it manifested good antineoplastic potency against both tested cell lines (IC 50  = 9 and 12 μM, respectively), beside its ability to inhibit the cell surface expression of CD133 by 50% suggesting a promising potential of effectively controlling the tumour by eradicating the tumour bulk and inhibiting the proliferation of the CSCs. Moreover, compounds 4a and 4c showed moderate activity against HT-29 (IC 50  = 21 and 29 μM, respectively) and MDA-MB-468 (IC 50  = 23 and 24 μM, respectively) cell lines, while they inhibited the CD133 expression by 14% and 48%, respectively. Finally, a single crystal X-ray diffraction was recorded for compound 4d.

  9. Design and optimization of N-acylhydrazone pyrimidine derivatives as E. coli PDHc E1 inhibitors: Structure-activity relationship analysis, biological evaluation and molecular docking study.

    Science.gov (United States)

    He, Haifeng; Xia, Hongying; Xia, Qin; Ren, Yanliang; He, Hongwu

    2017-10-15

    By targeting the thiamin diphosphate (ThDP) binding site of Escherichia coli (E. coli) pyruvate dehydrogenase multienzyme complex E1 (PDHc E1), a series of novel 'open-chain' classes of ThDP analogs A, B, and C with N-acylhydrazone moieties was designed and synthesized to explore their activities against E. coli PHDc E1 in vitro and their inhibitory activity against microbial diseases were further evaluated in vivo. As a result, A1-23 exhibited moderate to potent inhibitory activities against E. coli PDHc E1 (IC 50 =0.15-23.55μM). The potent inhibitors A13, A14, A15, C2, had strong inhibitory activities with IC 50 values of 0.60, 0.15, 0.39 and 0.34μM against E. coli PDHc E1 and with good enzyme-selective inhibition between microorganisms and mammals. Especially, the most powerful inhibitor A14 could 99.37% control Xanthimonas oryzae pv. Oryzae. Furthermore, the binding features of compound A14 within E. coli PDHc E1 were investigated to provide useful insights for the further construction of new inhibitor by molecular docking, site-directed mutagenesis, and enzymatic assays. The results indicated that A14 had most powerful inhibition against E. coli PDHc E1 due to the establishment of stronger interaction with Glu571, Met194, Glu522, Leu264 and Phe602 at active site of E.coli PDHc E1. It could be used as a lead compound for further optimization, and may have potential as a new microbicide. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. 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)

  11. 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.

  12. Development of the Biology Card Sorting Task to Measure Conceptual Expertise in Biology

    Science.gov (United States)

    Smith, Julia I.; Combs, Elijah D.; Nagami, Paul H.; Alto, Valerie M.; Goh, Henry G.; Gourdet, Muryam A. A.; Hough, Christina M.; Nickell, Ashley E.; Peer, Adrian G.; Coley, John D.; Tanner, Kimberly D.

    2013-01-01

    There are widespread aspirations to focus undergraduate biology education on teaching students to think conceptually like biologists; however, there is a dearth of assessment tools designed to measure progress from novice to expert biological conceptual thinking. We present the development of a novel assessment tool, the Biology Card Sorting Task, designed to probe how individuals organize their conceptual knowledge of biology. While modeled on tasks from cognitive psychology, this task is unique in its design to test two hypothesized conceptual frameworks for the organization of biological knowledge: 1) a surface feature organization focused on organism type and 2) a deep feature organization focused on fundamental biological concepts. In this initial investigation of the Biology Card Sorting Task, each of six analytical measures showed statistically significant differences when used to compare the card sorting results of putative biological experts (biology faculty) and novices (non–biology major undergraduates). Consistently, biology faculty appeared to sort based on hypothesized deep features, while non–biology majors appeared to sort based on either surface features or nonhypothesized organizational frameworks. Results suggest that this novel task is robust in distinguishing populations of biology experts and biology novices and may be an adaptable tool for tracking emerging biology conceptual expertise. PMID:24297290

  13. Design, Synthesis, and Biological Evaluation of 68Ga-DOTA-PA1 for Lung Cancer: A Novel PET Tracer for Multiple Somatostatin Receptor Imaging.

    Science.gov (United States)

    Liu, Fei; Liu, Teli; Xu, Xiaoxia; Guo, Xiaoyi; Li, Nan; Xiong, Chiyi; Li, Chun; Zhu, Hua; Yang, Zhi

    2018-02-05

    Most of the radiolabeled somatostatin analogues (SSAs) are specific for subtype somatostatin receptor 2 (SSTR 2 ). Lack of ligands targeting other subtypes of SSTRs, especially SSTR 1, SSTR 3 , and SSTR 5 , limited their applications in tumors of low SSTR 2 expression, including lung tumor. In this study, we aimed to design and synthesize a positron emission tomography (PET) radiotracer targeting multi-subtypes of SSTRs for PET imaging. PA1 peptide and its conjugate with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator or fluorescein isothiocyanate (FITC) at the N-terminal of the lysine position were synthesized. 68 Ga was chelated to DOTA-PA1 to obtain 68 Ga-DOTA-PA1 radiotracer. The stability, lipophilicity, binding affinity, and binding specificity of 68 Ga-DOTA-PA1 and FITC-PA1 were evaluated by various in vitro experiments. Micro-PET imaging of 68 Ga-DOTA-PA1 was performed in nude mice bearing A549 lung adenocarcinoma, as compared with 68 Ga-DOTA-(Tyr3)-octreotate ( 68 Ga-DOTA-TATE). Histological analysis of SSTR expression in A549 tumor tissues and human tumor tissues was conducted using immunofluorescence staining and immunohistochemical assay. 68 Ga-DOTA-PA1 had high radiochemical yield and radiochemical purity of over 95% and 99%, respectively. The radiotracer was stable in vitro in different buffers over a 2 h incubation period. Cell uptake of 68 Ga-DOTA-PA1 was 1.31-, 1.33-, and 1.90-fold that of 68 Ga-DOTA-TATE, which has high binding affinity only for SSTR 2 , after 2 h incubation in H520, PG, and A549 lung cancer cell lines, respectively. Micro-PET images of 68 Ga-DOTA-PA1 showed that the PET imaging signal correlated with the total expression of SSTRs, instead of SSTR 2 only, which was measured by Western blotting and immunofluorescence analysis in mice bearing A549 tumors. In summary, a novel PET radiotracer, 68 Ga-DOTA-PA1, targeting multi-subtypes of SSTRs, was successfully synthesized and was confirmed to be useful for PET

  14. Biological anti-TNF drugs

    DEFF Research Database (Denmark)

    Prado, Mônica Simon; Bendtzen, Klaus; Andrade, Luis Eduardo Coelho

    2017-01-01

    practice shows a significant percentage of individuals who do not exhibit the desired response. Loss of therapeutic benefit after initial successful response is designated secondary failure. Immune-biological agents are not self-antigens and are therefore potentially immunogenic. Secondary failure...... is frequently caused by antibodies against immune-biologicals, known as anti-drug antibodies (ADA). ADA that neutralize circulating immune-biologicals and/or promote their clearance can reduce treatment efficacy. Furthermore, ADA can induce adverse events by diverse immunological mechanisms. This review...... provides a comprehensive overview of ADA in rheumatoid arthritis patients treated with anti-TNF immune-biologicals, and explores the concept of therapeutic drug monitoring (TDM) as an effective strategy to improve therapeutic management. Expert opinion: Monitoring circulating ADA and therapeutic immune-biological...

  15. Endocrine active chemicals, pharmaceuticals, and other chemicals of concern in surface water, wastewater-treatment plant effluent, and bed sediment, and biological characteristics in selected streams, Minnesota-design, methods, and data, 2009

    Science.gov (United States)

    Lee, Kathy E.; Langer, Susan K.; Barber, Larry B.; Writer, Jeff H.; Ferrey, Mark L.; Schoenfuss, Heiko L.; Furlong, Edward T.; Foreman, William T.; Gray, James L.; ReVello, Rhiannon C.; Martinovic, Dalma; Woodruff, Olivia R.; Keefe, Steffanie H.; Brown, Greg K.; Taylor, Howard E.; Ferrer, Imma; Thurman, E. Michael

    2011-01-01

    This report presents the study design, environmental data, and quality-assurance data for an integrated chemical and biological study of selected streams or lakes that receive wastewater-treatment plant effluent in Minnesota. This study was a cooperative effort of the U.S. Geological Survey, the Minnesota Pollution Control Agency, St. Cloud State University, the University of St. Thomas, and the University of Colorado. The objective of the study was to identify distribution patterns of endocrine active chemicals, pharmaceuticals, and other organic and inorganic chemicals of concern indicative of wastewater effluent, and to identify biological characteristics of estrogenicity and fish responses in the same streams. The U.S. Geological Survey collected and analyzed water, bed-sediment, and quality-assurance samples, and measured or recorded streamflow once at each sampling location from September through November 2009. Sampling locations included surface water and wastewater-treatment plant effluent. Twenty-five wastewater-treatment plants were selected to include continuous flow and periodic release facilities with differing processing steps (activated sludge or trickling filters) and plant design flows ranging from 0.002 to 10.9 cubic meters per second (0.04 to 251 million gallons per day) throughout Minnesota in varying land-use settings. Water samples were collected from the treated effluent of the 25 wastewater-treatment plants and at one point upstream from and one point downstream from wastewater-treatment plant effluent discharges. Bed-sediment samples also were collected at each of the stream or lake locations. Water samples were analyzed for major ions, nutrients, trace elements, pharmaceuticals, phytoestrogens and pharmaceuticals, alkylphenols and other neutral organic chemicals, carboxylic acids, and steroidal hormones. A subset (25 samples) of the bed-sediment samples were analyzed for carbon, wastewater-indicator chemicals, and steroidal hormones; the

  16. A Brief Introduction to Chinese Biological Biological

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Chinese Biological Abstracts sponsored by the Library, the Shanghai Institutes for Biological Sciences, the Biological Documentation and Information Network, all of the Chinese Academy of Sciences, commenced publication in 1987 and was initiated to provide access to the Chinese information in the field of biology.

  17. Basic radiotherapy physics and biology

    CERN Document Server

    Chang, David S; Das, Indra J; Mendonca, Marc S; Dynlacht, Joseph R

    2014-01-01

    This book is a concise and well-illustrated review of the physics and biology of radiation therapy intended for radiation oncology residents, radiation therapists, dosimetrists, and physicists. It presents topics that are included on the Radiation Therapy Physics and Biology examinations and is designed with the intent of presenting information in an easily digestible format with maximum retention in mind. The inclusion of mnemonics, rules of thumb, and reader-friendly illustrations throughout the book help to make difficult concepts easier to grasp. Basic Radiotherapy Physics and Biology is a

  18. Dominating biological networks.

    Directory of Open Access Journals (Sweden)

    Tijana Milenković

    Full Text Available Proteins are essential macromolecules of life that carry out most cellular processes. Since proteins aggregate to perform function, and since protein-protein interaction (PPI networks model these aggregations, one would expect to uncover new biology from PPI network topology. Hence, using PPI networks to predict protein function and role of protein pathways in disease has received attention. A debate remains open about whether network properties of "biologically central (BC" genes (i.e., their protein products, such as those involved in aging, cancer, infectious diseases, or signaling and drug-targeted pathways, exhibit some topological centrality compared to the rest of the proteins in the human PPI network.To help resolve this debate, we design new network-based approaches and apply them to get new insight into biological function and disease. We hypothesize that BC genes have a topologically central (TC role in the human PPI network. We propose two different concepts of topological centrality. We design a new centrality measure to capture complex wirings of proteins in the network that identifies as TC those proteins that reside in dense extended network neighborhoods. Also, we use the notion of domination and find dominating sets (DSs in the PPI network, i.e., sets of proteins such that every protein is either in the DS or is a neighbor of the DS. Clearly, a DS has a TC role, as it enables efficient communication between different network parts. We find statistically significant enrichment in BC genes of TC nodes and outperform the existing methods indicating that genes involved in key biological processes occupy topologically complex and dense regions of the network and correspond to its "spine" that connects all other network parts and can thus pass cellular signals efficiently throughout the network. To our knowledge, this is the first study that explores domination in the context of PPI networks.

  19. Synthesis and biological evaluation of some N-(3-(1H-tetrazol-5-yl) phenyl)acetamide derivatives as novel non-carboxylic PTP1B inhibitors designed through bioisosteric modulation.

    Science.gov (United States)

    Maheshwari, Neelesh; Karthikeyan, Chandrabose; Bhadada, Shraddha V; Sahi, Chandan; Verma, Amit K; Hari Narayana Moorthy, N S; Trivedi, Piyush

    2018-06-08

    Described herein is the synthesis and biological evaluation of a series of non-carboxylic inhibitors of Protein Tyrosine Phosphatase 1B designed using bioisosteric replacement strategy. Six N-(3-(1H-tetrazol-5-yl)phenyl)acetamide derivatives designed employing the aforementioned strategy were synthesized and screened for PTP1B inhibitory activity. Among the synthesized compounds, compound NM-03 exhibited the most potent inhibitory activity with IC 50 value of 4.48 µM. Docking studies with NM-03 revealed the key interactions with desired amino acids in the binding site of PTP1B. Furthermore, compound NM-03 also elicited good in vivo activity. Taken together, the results of this study establish N-(3-(1H-tetrazole-5-yl)phenyl)-2-(benzo[d]oxazol-2-ylthio)acetamide (NM-03) as a valuable lead molecule with great potential for PTP1B inhibitor development targeting diabetes. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Biology of Bilirubin Photoisomers.

    Science.gov (United States)

    Hansen, Thor Willy Ruud

    2016-06-01

    Phototherapy is the main treatment for neonatal hyperbilirubinemia. In acute treatment of extreme hyperbilirubinemia, intensive phototherapy may have a role in 'detoxifying' the bilirubin molecule to more polar photoisomers, which should be less prone to crossing the blood-brain barrier, providing a 'brain-sparing' effect. This article reviews the biology of bilirubin isomers. Although there is evidence supporting the lower toxicity of bilirubin photoisomers, there are studies showing the opposite. There are methodologic weaknesses in most studies and better-designed experiments are needed. In an infant acutely threatened by bilirubin-induced brain damage, intensified phototherapy should be used expediently and aggressively. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Structural biological composites: An overview

    Science.gov (United States)

    Meyers, Marc A.; Lin, Albert Y. M.; Seki, Yasuaki; Chen, Po-Yu; Kad, Bimal K.; Bodde, Sara

    2006-07-01

    Biological materials are complex composites that are hierarchically structured and multifunctional. Their mechanical properties are often outstanding, considering the weak constituents from which they are assembled. They are for the most part composed of brittle (often, mineral) and ductile (organic) components. These complex structures, which have risen from millions of years of evolution, are inspiring materials scientists in the design of novel materials. This paper discusses the overall design principles in biological structural composites and illustrates them for five examples; sea spicules, the abalone shell, the conch shell, the toucan and hornbill beaks, and the sheep crab exoskeleton.

  2. Developments in the Tools and Methodologies of Synthetic Biology

    Science.gov (United States)

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

    2014-01-01

    Synthetic biology is principally concerned with the rational design and engineering of biologically based parts, devices, or systems. However, biological systems are generally complex and unpredictable, and are therefore, intrinsically difficult to engineer. In order to address these fundamental challenges, synthetic biology is aiming to unify a “body of knowledge” from several foundational scientific fields, within the context of a set of engineering principles. This shift in perspective is enabling synthetic biologists to address complexity, such that robust biological systems can be designed, assembled, and tested as part of a biological design cycle. The design cycle takes a forward-design approach in which a biological system is specified, modeled, analyzed, assembled, and its functionality tested. At each stage of the design cycle, an expanding repertoire of tools is being developed. In this review, we highlight several of these tools in terms of their applications and benefits to the synthetic biology community. PMID:25505788

  3. Developments in the tools and methodologies of synthetic biology

    Directory of Open Access Journals (Sweden)

    Richard eKelwick

    2014-11-01

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

  4. Engineering Design and Operation Report: Biological ...

    Science.gov (United States)

    Many regions in the United States have excessive levels of ammonia in their drinking water sources (e.g., ground and surface waters) as a result of naturally occurring processes, agricultural and urban runoff, concentrated animal feeding operations, municipal wastewater treatment plants, and other sources. Ammonia is not regulated by the U.S. Environmental Protection Agency (EPA) as a contaminant. Based on a 2003 World Health Organization (WHO) assessment, ammonia levels in groundwater are typically below 0.2 milligrams per liter (mg/L), and do not pose a direct health concern at levels expected in drinking water (WHO 2003); however, they may pose a concern when nitrification of significant levels of ammonia from the source water occurs in the drinking water distribution system. Specifically, this nitrification, which is the conversion of the ammonia to nitrite and nitrate by bacteria, leads to water quality issues, such as potential corrosion problems, oxidant demand, taste and odor complaints, and elevated nitrite levels (Bremer et al.,2001; Fleming et al., 2005; Lee et al., 1980; Odell et al., 1996; Rittman & Snoeyink, 1984; Suffet et al., 1996). The EPA’s regulatory limits for nitrite and nitrate (at the entry point to the distribution system) are 0.1 and 10 mg N/L, respectively. Ammonia in water may also pose problems with water treatment effectiveness. For example, in source waters containing both ammonia and arsenic, the ammonia may negatively impact

  5. ENGINEERING DESIGN CONFIGURATIONS FOR BIOLOGICAL AMMONIA REMOVAL

    Science.gov (United States)

    Many regions in the United States have excessive levels of nutrients including ammonia in their source waters. For example, farming and agricultural sources of ammonia in the Midwest contribute to relatively high levels of ammonia in many ground waters. Although ammonia in water ...

  6. Thermal and biological gasification

    Energy Technology Data Exchange (ETDEWEB)

    Overend, R.P.; Rivard, C.J. [National Renewable Energy Lab., Golden, CO (United States)

    1993-12-31

    Gasification is being developed to enable a diverse range of biomass resources to meet modern secondary energy uses, especially in the electrical utility sector. Biological or anaerobic gasification in US landfills has resulted in the installation of almost 500 MW(e) of capacity and represents the largest scale application of gasification technology today. The development of integrated gasification combined cycle generation for coal technologies is being paralleled by bagasse and wood thermal gasification systems in Hawaii and Scandinavia, and will lead to significant deployment in the next decade as the current scale-up activities are commercialized. The advantages of highly reactive biomass over coal in the design of process units are being realized as new thermal gasifiers are being scaled up to produce medium-energy-content gas for conversion to synthetic natural gas and transportation fuels and to hydrogen for use in fuel cells. The advent of high solids anaerobic digestion reactors is leading to commercialization of controlled municipal solid waste biological gasification rather than landfill application. In both thermal and biological gasification, high rate process reactors are a necessary development for economic applications that address waste and residue management and the production and use of new crops for energy. The environmental contribution of biomass in reducing greenhouse gas emission will also be improved.

  7. Fostering synergy between cell biology and systems biology.

    Science.gov (United States)

    Eddy, James A; Funk, Cory C; Price, Nathan D

    2015-08-01

    In the shared pursuit of elucidating detailed mechanisms of cell function, systems biology presents a natural complement to ongoing efforts in cell biology. Systems biology aims to characterize biological systems through integrated and quantitative modeling of cellular information. The process of model building and analysis provides value through synthesizing and cataloging information about cells and molecules, predicting mechanisms and identifying generalizable themes, generating hypotheses and guiding experimental design, and highlighting knowledge gaps and refining understanding. In turn, incorporating domain expertise and experimental data is crucial for building towards whole cell models. An iterative cycle of interaction between cell and systems biologists advances the goals of both fields and establishes a framework for mechanistic understanding of the genome-to-phenome relationship. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  8. Development of the Biology Card Sorting Task to Measure Conceptual Expertise in Biology

    Science.gov (United States)

    Smith, Julia I.; Combs, Elijah D.; Nagami, Paul H.; Alto, Valerie M.; Goh, Henry G.; Gourdet, Muryam A. A.; Hough, Christina M.; Nickell, Ashley E.; Peer, Adrian G.; Coley, John D.; Tanner, Kimberly D.

    2013-01-01

    There are widespread aspirations to focus undergraduate biology education on teaching students to think conceptually like biologists; however, there is a dearth of assessment tools designed to measure progress from novice to expert biological conceptual thinking. We present the development of a novel assessment tool, the Biology Card Sorting Task,…

  9. Using the Biology Card Sorting Task to Measure Changes in Conceptual Expertise during Postsecondary Biology Education

    Science.gov (United States)

    Bissonnette, Sarah A.; Combs, Elijah D.; Nagami, Paul H.; Byers, Victor; Fernandez, Juliana; Le, Dinh; Realin, Jared; Woodham, Selina; Smith, Julia I.; Tanner, Kimberly D.

    2017-01-01

    While there have been concerted efforts to reform undergraduate biology toward teaching students to organize their conceptual knowledge like experts, there are few tools that attempt to measure this. We previously developed the Biology Card Sorting Task (BCST), designed to probe how individuals organize their conceptual biological knowledge.…

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

    Directory of Open Access Journals (Sweden)

    Bor-Sen Chen

    2013-10-01

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

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

    Science.gov (United States)

    Chen, Bor-Sen; Wu, Chia-Chou

    2013-01-01

    Systems biology aims at achieving a system-level understanding of living organisms and applying this knowledge to various fields such as synthetic biology, metabolic engineering, and medicine. System-level understanding of living organisms can be derived from insight into: (i) system structure and the mechanism of biological networks such as gene regulation, protein interactions, signaling, and metabolic pathways; (ii) system dynamics of biological networks, which provides an understanding of stability, robustness, and transduction ability through system identification, and through system analysis methods; (iii) system control methods at different levels of biological networks, which provide an understanding of systematic mechanisms to robustly control system states, minimize malfunctions, and provide potential therapeutic targets in disease treatment; (iv) systematic design methods for the modification and construction of biological networks with desired behaviors, which provide system design principles and system simulations for synthetic biology designs and systems metabolic engineering. This review describes current developments in systems biology, systems synthetic biology, and systems metabolic engineering for engineering and biology researchers. We also discuss challenges and future prospects for systems biology and the concept of systems biology as an integrated platform for bioinformatics, systems synthetic biology, and systems metabolic engineering. PMID:24709875

  12. Integrating quantitative thinking into an introductory biology course improves students' mathematical reasoning in biological contexts.

    Science.gov (United States)

    Hester, Susan; Buxner, Sanlyn; Elfring, Lisa; Nagy, Lisa

    2014-01-01

    Recent calls for improving undergraduate biology education have emphasized the importance of students learning to apply quantitative skills to biological problems. Motivated by students' apparent inability to transfer their existing quantitative skills to biological contexts, we designed and taught an introductory molecular and cell biology course in which we integrated application of prerequisite mathematical skills with biology content and reasoning throughout all aspects of the course. In this paper, we describe the principles of our course design and present illustrative examples of course materials integrating mathematics and biology. We also designed an outcome assessment made up of items testing students' understanding of biology concepts and their ability to apply mathematical skills in biological contexts and administered it as a pre/postcourse test to students in the experimental section and other sections of the same course. Precourse results confirmed students' inability to spontaneously transfer their prerequisite mathematics skills to biological problems. Pre/postcourse outcome assessment comparisons showed that, compared with students in other sections, students in the experimental section made greater gains on integrated math/biology items. They also made comparable gains on biology items, indicating that integrating quantitative skills into an introductory biology course does not have a deleterious effect on students' biology learning.

  13. Integrating Quantitative Thinking into an Introductory Biology Course Improves Students’ Mathematical Reasoning in Biological Contexts

    Science.gov (United States)

    Hester, Susan; Buxner, Sanlyn; Elfring, Lisa; Nagy, Lisa

    2014-01-01

    Recent calls for improving undergraduate biology education have emphasized the importance of students learning to apply quantitative skills to biological problems. Motivated by students’ apparent inability to transfer their existing quantitative skills to biological contexts, we designed and taught an introductory molecular and cell biology course in which we integrated application of prerequisite mathematical skills with biology content and reasoning throughout all aspects of the course. In this paper, we describe the principles of our course design and present illustrative examples of course materials integrating mathematics and biology. We also designed an outcome assessment made up of items testing students’ understanding of biology concepts and their ability to apply mathematical skills in biological contexts and administered it as a pre/postcourse test to students in the experimental section and other sections of the same course. Precourse results confirmed students’ inability to spontaneously transfer their prerequisite mathematics skills to biological problems. Pre/postcourse outcome assessment comparisons showed that, compared with students in other sections, students in the experimental section made greater gains on integrated math/biology items. They also made comparable gains on biology items, indicating that integrating quantitative skills into an introductory biology course does not have a deleterious effect on students’ biology learning. PMID:24591504

  14. Synthetic Biology and Personalized Medicine

    Science.gov (United States)

    Jain, K.K.

    2013-01-01

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

  15. Biological effects of radiation

    International Nuclear Information System (INIS)

    2013-01-01

    This fourth chapter presents: cell structure and metabolism; radiation interaction with biological tissues; steps of the production of biological effect of radiation; radiosensitivity of tissues; classification of biological effects; reversibility, transmissivity and influence factors; pre-natal biological effects; biological effects in therapy and syndrome of acute irradiation

  16. 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.

  17. Synthetic Biology for Specialty Chemicals.

    Science.gov (United States)

    Markham, Kelly A; Alper, Hal S

    2015-01-01

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

  18. Fused heterocyclic compounds bearing bridgehead nitrogen as potent HIV-1 NNRTIs. Part 1: design, synthesis and biological evaluation of novel 5,7-disubstituted pyrazolo[1,5-a]pyrimidine derivatives.

    Science.gov (United States)

    Tian, Ye; Du, Deping; Rai, Diwakar; Wang, Liu; Liu, Huiqing; Zhan, Peng; De Clercq, Erik; Pannecouque, Christophe; Liu, Xinyong

    2014-04-01

    In our continuous efforts to identify novel potent HIV-1 NNRTIs, a novel class of 5,7-disubstituted pyrazolo[1,5-a]pyrimidine derivatives were rationally designed, synthesized and evaluated for their anti-HIV activities in MT4 cell cultures. Biological results showed that most of the tested compounds displayed excellent activity against wild-type HIV-1 with a wide range of EC50 values from 5.98 to 0.07μM. Among the active compounds, 5a was found to be the most promising analogue with an EC50 of 0.07μM against wild-type HIV-1 and very high selectivity index (SI, 3999). Compound 5a was more effective than the reference drugs nevirapine (by 2-fold) and delavirdine (by 2-fold). In order to further confirm their binding target, an HIV-1 RT inhibitory assay was also performed. Furthermore, SAR analysis among the newly synthesized compounds was discussed and the binding mode of the active compound 5a was rationalized by molecular modeling studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Cardiovascular toxicities of biological therapies

    DEFF Research Database (Denmark)

    Ryberg, Marianne

    2013-01-01

    The development of biological therapy is based on growing knowledge regarding the molecular changes required in cells for the development and progression of cancer to occur. Molecular targeted therapy is designed to inhibit the major molecular pathways identified as essential for a specific...

  20. 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

  1. Hanford Site Biological Resources Mitigation Strategy

    International Nuclear Information System (INIS)

    Sackschewsky, Michael R

    2003-01-01

    The Biological Resources Mitigation Strategy (BRMiS), as part of a broader biological resource policy, is designed to aid the U.S. Department of Energy, Richland Operations Office (DOE-RL) in balancing its primary missions of waste cleanup, technology development, and economic diversification with its stewardship responsibilities for the biological resources it administers. This strategy will be applied to all DOE-RL programs as well as all contractor and subcontractor activities

  2. Where Synthetic Biology Meets ET

    Science.gov (United States)

    Rothschild, Lynn J.

    2016-01-01

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

  3. Molecular biology of the cell

    CERN Document Server

    Alberts, Bruce; Lewis, Julian

    2000-01-01

    Molecular Biology of the Cell is the classic in-dept text reference in cell biology. By extracting the fundamental concepts from this enormous and ever-growing field, the authors tell the story of cell biology, and create a coherent framework through which non-expert readers may approach the subject. Written in clear and concise language, and beautifully illustrated, the book is enjoyable to read, and it provides a clear sense of the excitement of modern biology. Molecular Biology of the Cell sets forth the current understanding of cell biology (completely updated as of Autumn 2001), and it explores the intriguing implications and possibilities of the great deal that remains unknown. The hallmark features of previous editions continue in the Fourth Edition. The book is designed with a clean and open, single-column layout. The art program maintains a completely consistent format and style, and includes over 1,600 photographs, electron micrographs, and original drawings by the authors. Clear and concise concept...

  4. Biology Reflective Assessment Curriculum

    Science.gov (United States)

    Bayley, Cheryl Ann

    Often students and educators view assessments as an obligation and finality for a unit. In the current climate of high-stakes testing and accountability, the balance of time, resources and emphasis on students' scores related to assessment have been slanted considerably toward the summative side. This tension between assessment for accountability and assessment to inform teaching strains instruction and educators' ability to use that information to design learning opportunities that help students develop deeper conceptual understanding. A substantive body of research indicates that formative and reflective assessment can significantly improve student learning. Biology Reflective Assessment Curriculum (BRAC) examines support provided for high school science students through assessment practices. This investigation incorporates the usage of reflective assessments as a guiding practice for differentiated instruction and student choice. Reflective assessment is a metacognitive strategy that promotes self-monitoring and evaluation. The goals of the curriculum are to promote self-efficacy and conceptual understanding in students learning biology through developing their metacognitive awareness. BRAC was implemented in a high school biology classroom. Data from assessments, metacognitive surveys, self-efficacy surveys, reflective journals, student work, a culminating task and field notes were used to evaluate the effectiveness of the curriculum. The results suggest that students who develop their metacognitive skills developed a deeper conceptual understanding and improved feelings of self-efficacy when they were engaged in a reflective assessment unit embedded with student choice. BRAC is a tool for teachers to use assessments to assist students in becoming metacognitive and to guide student choice in learning opportunities.

  5. 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

  6. Dyneins: structure, biology and disease

    National Research Council Canada - National Science Library

    King, Stephen M

    2012-01-01

    .... From bench to bedside, Dynein: Structure, Biology and Disease offers research on fundamental cellular processes to researchers and clinicians across developmental biology, cell biology, molecular biology, biophysics, biomedicine...

  7. Biological conversion system

    Science.gov (United States)

    Scott, C.D.

    A system for bioconversion of organic material comprises a primary bioreactor column wherein a biological active agent (zymomonas mobilis) converts the organic material (sugar) to a product (alcohol), a rejuvenator column wherein the biological activity of said biological active agent is enhanced, and means for circulating said biological active agent between said primary bioreactor column and said rejuvenator column.

  8. Computational structural biology: methods and applications

    National Research Council Canada - National Science Library

    Schwede, Torsten; Peitsch, Manuel Claude

    2008-01-01

    ... sequencing reinforced the observation that structural information is needed to understand the detailed function and mechanism of biological molecules such as enzyme reactions and molecular recognition events. Furthermore, structures are obviously key to the design of molecules with new or improved functions. In this context, computational structural biology...

  9. 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

  10. Translational environmental biology: cell biology informing conservation.

    Science.gov (United States)

    Traylor-Knowles, Nikki; Palumbi, Stephen R

    2014-05-01

    Typically, findings from cell biology have been beneficial for preventing human disease. However, translational applications from cell biology can also be applied to conservation efforts, such as protecting coral reefs. Recent efforts to understand the cell biological mechanisms maintaining coral health such as innate immunity and acclimatization have prompted new developments in conservation. Similar to biomedicine, we urge that future efforts should focus on better frameworks for biomarker development to protect coral reefs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. 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.

  12. Biological effectiveness of antiproton annihilation

    DEFF Research Database (Denmark)

    Holzscheiter, M.H.; Agazaryan, N.; Bassler, Niels

    2004-01-01

    We describe an experiment designed to determine whether or not the densely ionizing particles emanating from the annihilation of antiprotons produce an increase in ‘‘biological dose’’ in the vicinity of the narrow Bragg peak for antiprotons compared to protons. This experiment is the first direct...... measurement of the biological effects of antiproton annihilation. The experiment has been approved by the CERN Research Board for running at the CERN Antiproton Decelerator (AD) as AD-4/ACE (Antiproton Cell Experiment) and has begun data taking in June of 2003. The background, description and the current...

  13. Biological effectiveness of antiproton annihilation

    CERN Document Server

    Holzscheiter, Michael H.; Bassler, Niels; Beyer, Gerd; De Marco, John J.; Doser, Michael; Ichioka, Toshiyasu; Iwamoto, Keisuke S.; Knudsen, Helge V.; Landua, Rolf; Maggiore, Carl; McBride, William H.; Møller, Søren Pape; Petersen, Jorgen; Smathers, James B.; Skarsgard, Lloyd D.; Solberg, Timothy D.; Uggerhøj, Ulrik I.; Withers, H.Rodney; Vranjes, Sanja; Wong, Michelle; Wouters, Bradly G.

    2004-01-01

    We describe an experiment designed to determine whether or not the densely ionizing particles emanating from the annihilation of antiprotons produce an increase in “biological dose” in the vicinity of the narrow Bragg peak for antiprotons compared to protons. This experiment is the first direct measurement of the biological effects of antiproton annihilation. The experiment has been approved by the CERN Research Board for running at the CERN Antiproton Decelerator (AD) as AD-4/ACE (Antiproton Cell Experiment) and has begun data taking in June of 2003. The background, description and the current status of the experiment are given.

  14. Computational Systems Chemical Biology

    OpenAIRE

    Oprea, Tudor I.; May, Elebeoba E.; Leitão, Andrei; Tropsha, Alexander

    2011-01-01

    There is a critical need for improving the level of chemistry awareness in systems biology. The data and information related to modulation of genes and proteins by small molecules continue to accumulate at the same time as simulation tools in systems biology and whole body physiologically-based pharmacokinetics (PBPK) continue to evolve. We called this emerging area at the interface between chemical biology and systems biology systems chemical biology, SCB (Oprea et al., 2007).

  15. Pulsed Electric Fields for Biological Weapons Defense

    National Research Council Canada - National Science Library

    Gundersen, Martin A

    2008-01-01

    Pulsed power for biological investigations newly developed at USC include a fast diode-based systems designed to drive cell suspensions in a microscope slide electrode microchamber for observations...

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

    Science.gov (United States)

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

    2014-03-27

    Synthetic biology seeks to extend approaches from engineering and computation to redesign of biology, with goals such as generating new chemicals, improving human health, and addressing environmental issues. Early on, several guiding principles of synthetic biology were articulated, including design according to specification, separation of design from fabrication, use of standardized biological parts and organisms, and abstraction. We review the utility of these principles over the past decade in light of the field's accomplishments in building complex systems based on microbial transcription and metabolism and describe the progress in mammalian cell engineering. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Some nonlinear challenges in biology

    International Nuclear Information System (INIS)

    Mosconi, Francesco; Julou, Thomas; Desprat, Nicolas; Sinha, Deepak Kumar; Allemand, Jean-François; Croquette, Vincent; Bensimon, David

    2008-01-01

    Driven by a deluge of data, biology is undergoing a transition to a more quantitative science. Making sense of the data, building new models, asking the right questions and designing smart experiments to answer them are becoming ever more relevant. In this endeavour, nonlinear approaches can play a fundamental role. The biochemical reactions that underlie life are very often nonlinear. The functional features exhibited by biological systems at all levels (from the activity of an enzyme to the organization of a colony of ants, via the development of an organism or a functional module like the one responsible for chemotaxis in bacteria) are dynamically robust. They are often unaffected by order of magnitude variations in the dynamical parameters, in the number or concentrations of actors (molecules, cells, organisms) or external inputs (food, temperature, pH, etc). This type of structural robustness is also a common feature of nonlinear systems, exemplified by the fundamental role played by dynamical fixed points and attractors and by the use of generic equations (logistic map, Fisher–Kolmogorov equation, the Stefan problem, etc.) in the study of a plethora of nonlinear phenomena. However, biological systems differ from these examples in two important ways: the intrinsic stochasticity arising from the often very small number of actors and the role played by evolution. On an evolutionary time scale, nothing in biology is frozen. The systems observed today have evolved from solutions adopted in the past and they will have to adapt in response to future conditions. The evolvability of biological system uniquely characterizes them and is central to biology. As the great biologist T Dobzhansky once wrote: 'nothing in biology makes sense except in the light of evolution'. (open problem)

  18. Applicability of Computational Systems Biology in Toxicology

    DEFF Research Database (Denmark)

    Kongsbak, Kristine Grønning; Hadrup, Niels; Audouze, Karine Marie Laure

    2014-01-01

    be used to establish hypotheses on links between the chemical and human diseases. Such information can also be applied for designing more intelligent animal/cell experiments that can test the established hypotheses. Here, we describe how and why to apply an integrative systems biology method......Systems biology as a research field has emerged within the last few decades. Systems biology, often defined as the antithesis of the reductionist approach, integrates information about individual components of a biological system. In integrative systems biology, large data sets from various sources...... and databases are used to model and predict effects of chemicals on, for instance, human health. In toxicology, computational systems biology enables identification of important pathways and molecules from large data sets; tasks that can be extremely laborious when performed by a classical literature search...

  19. 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).

  20. Biology of Blood

    Science.gov (United States)

    ... switch to the Professional version Home Blood Disorders Biology of Blood Overview of Blood Resources In This ... Version. DOCTORS: Click here for the Professional Version Biology of Blood Overview of Blood Components of Blood ...

  1. Biological basis of detoxication

    National Research Council Canada - National Science Library

    Caldwell, John; Jakoby, William B

    1983-01-01

    This volume considers that premise that most of the major patterns of biological conversion of foreign compounds are known and may have predictive value in assessing the biological course for novel compounds...

  2. Fusion of biological membranes

    Indian Academy of Sciences (India)

    Home; Journals; Pramana – Journal of Physics; Volume 64; Issue 6. Fusion of biological membranes. K Katsov M Müller M Schick. Invited Talks:- Topic 11. Biologically motivated problems (protein-folding models, dynamics at the scale of the cell; biological networks, evolution models, etc.) Volume 64 Issue 6 June 2005 pp ...

  3. Radiation biology. Chapter 20

    Energy Technology Data Exchange (ETDEWEB)

    Wondergem, J. [International Atomic Energy Agency, Vienna (Austria)

    2014-09-15

    Radiation biology (radiobiology) is the study of the action of ionizing radiations on living matter. This chapter gives an overview of the biological effects of ionizing radiation and discusses the physical, chemical and biological variables that affect dose response at the cellular, tissue and whole body levels at doses and dose rates relevant to diagnostic radiology.

  4. General Biology Syllabus.

    Science.gov (United States)

    Hunter, Scott; Watthews, Thomas

    This syllabus has been developed as an alternative to Regents biology and is intended for the average student who could benefit from an introductory biology course. It is divided into seven major units dealing with, respectively: (1) similarities among living things; (2) human biology (focusing on nutrition, transport, respiration, excretion, and…

  5. Upgrading Undergraduate Biology Education

    Science.gov (United States)

    Musante, Susan

    2011-01-01

    On many campuses throughout the country, undergraduate biology education is in serious need of an upgrade. During the past few decades, the body of biological knowledge has grown exponentially, and as a research endeavor, the practice of biology has evolved. Education research has also made great strides, revealing many new insights into how…

  6. Chemistry and Biology

    Science.gov (United States)

    Wigston, David L.

    1970-01-01

    Discusses the relationship between chemisty and biology in the science curriculum. Points out the differences in perception of the disciplines, which the physical scientists favoring reductionism. Suggests that biology departments offer a special course for chemistry students, just as the chemistry departments have done for biology students.…

  7. 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.

  8. 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.

  9. pGLO Mutagenesis: A Laboratory Procedure in Molecular Biology for Biology Students

    Science.gov (United States)

    Bassiri, Eby A.

    2011-01-01

    A five-session laboratory project was designed to familiarize or increase the laboratory proficiency of biology students and others with techniques and instruments commonly used in molecular biology research laboratories and industries. In this project, the EZ-Tn5 transposon is used to generate and screen a large number of cells transformed with…

  10. Quantum biological information theory

    CERN Document Server

    Djordjevic, Ivan B

    2016-01-01

    This book is a self-contained, tutorial-based introduction to quantum information theory and quantum biology. It serves as a single-source reference to the topic for researchers in bioengineering, communications engineering, electrical engineering, applied mathematics, biology, computer science, and physics. The book provides all the essential principles of the quantum biological information theory required to describe the quantum information transfer from DNA to proteins, the sources of genetic noise and genetic errors as well as their effects. Integrates quantum information and quantum biology concepts; Assumes only knowledge of basic concepts of vector algebra at undergraduate level; Provides a thorough introduction to basic concepts of quantum information processing, quantum information theory, and quantum biology; Includes in-depth discussion of the quantum biological channel modelling, quantum biological channel capacity calculation, quantum models of aging, quantum models of evolution, quantum models o...

  11. Introductory Biology Labs... They Just Aren't Sexy Enough!

    Science.gov (United States)

    Cotner, Sehoya; Gallup, Gordon G., Jr.

    2011-01-01

    The typical introductory biology curriculum includes the nature of science, evolution and genetics. Laboratory activities are designed to engage students in typical subject areas ranging from cell biology and physiology, to ecology and evolution. There are few, if any, laboratory classes exploring the biology and evolution of human sexual…

  12. Design, synthesis, and biological evaluation of novel 1,2-diaryl-4-substituted-benzylidene-5(4H)-imidazolone derivatives as cytotoxic agents and COX-2/LOX inhibitors

    Czech Academy of Sciences Publication Activity Database

    Lamie, P.F.; Philoppes, J.N.; Rárová, Lucie

    2018-01-01

    Roč. 351, 3-4 (2018), č. článku e1700311. ISSN 0365-6233 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : anti-inflammatory * cytotoxicity * diaryl imidazolone derivatives * molecular docking study Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemical research methods Impact factor: 1.994, year: 2016

  13. Systems Biology of Industrial Microorganisms

    Science.gov (United States)

    Papini, Marta; Salazar, Margarita; Nielsen, Jens

    The field of industrial biotechnology is expanding rapidly as the chemical industry is looking towards more sustainable production of chemicals that can be used as fuels or building blocks for production of solvents and materials. In connection with the development of sustainable bioprocesses, it is a major challenge to design and develop efficient cell factories that can ensure cost efficient conversion of the raw material into the chemical of interest. This is achieved through metabolic engineering, where the metabolism of the cell factory is engineered such that there is an efficient conversion of sugars, the typical raw materials in the fermentation industry, into the desired product. However, engineering of cellular metabolism is often challenging due to the complex regulation that has evolved in connection with adaptation of the different microorganisms to their ecological niches. In order to map these regulatory structures and further de-regulate them, as well as identify ingenious metabolic engineering strategies that full-fill mass balance constraints, tools from systems biology can be applied. This involves both high-throughput analysis tools like transcriptome, proteome and metabolome analysis, as well as the use of mathematical modeling to simulate the phenotypes resulting from the different metabolic engineering strategies. It is in fact expected that systems biology may substantially improve the process of cell factory development, and we therefore propose the term Industrial Systems Biology for how systems biology will enhance the development of industrial biotechnology for sustainable chemical production.

  14. Standard biological parts knowledgebase.

    Directory of Open Access Journals (Sweden)

    Michal Galdzicki

    2011-02-01

    Full Text Available We have created the Knowledgebase of Standard Biological Parts (SBPkb as a publically accessible Semantic Web resource for synthetic biology (sbolstandard.org. The SBPkb allows researchers to query and retrieve standard biological parts for research and use in synthetic biology. Its initial version includes all of the information about parts stored in the Registry of Standard Biological Parts (partsregistry.org. SBPkb transforms this information so that it is computable, using our semantic framework for synthetic biology parts. This framework, known as SBOL-semantic, was built as part of the Synthetic Biology Open Language (SBOL, a project of the Synthetic Biology Data Exchange Group. SBOL-semantic represents commonly used synthetic biology entities, and its purpose is to improve the distribution and exchange of descriptions of biological parts. In this paper, we describe the data, our methods for transformation to SBPkb, and finally, we demonstrate the value of our knowledgebase with a set of sample queries. We use RDF technology and SPARQL queries to retrieve candidate "promoter" parts that are known to be both negatively and positively regulated. This method provides new web based data access to perform searches for parts that are not currently possible.

  15. Standard Biological Parts Knowledgebase

    Science.gov (United States)

    Galdzicki, Michal; Rodriguez, Cesar; Chandran, Deepak; Sauro, Herbert M.; Gennari, John H.

    2011-01-01

    We have created the Knowledgebase of Standard Biological Parts (SBPkb) as a publically accessible Semantic Web resource for synthetic biology (sbolstandard.org). The SBPkb allows researchers to query and retrieve standard biological parts for research and use in synthetic biology. Its initial version includes all of the information about parts stored in the Registry of Standard Biological Parts (partsregistry.org). SBPkb transforms this information so that it is computable, using our semantic framework for synthetic biology parts. This framework, known as SBOL-semantic, was built as part of the Synthetic Biology Open Language (SBOL), a project of the Synthetic Biology Data Exchange Group. SBOL-semantic represents commonly used synthetic biology entities, and its purpose is to improve the distribution and exchange of descriptions of biological parts. In this paper, we describe the data, our methods for transformation to SBPkb, and finally, we demonstrate the value of our knowledgebase with a set of sample queries. We use RDF technology and SPARQL queries to retrieve candidate “promoter” parts that are known to be both negatively and positively regulated. This method provides new web based data access to perform searches for parts that are not currently possible. PMID:21390321

  16. Standard biological parts knowledgebase.

    Science.gov (United States)

    Galdzicki, Michal; Rodriguez, Cesar; Chandran, Deepak; Sauro, Herbert M; Gennari, John H

    2011-02-24

    We have created the Knowledgebase of Standard Biological Parts (SBPkb) as a publically accessible Semantic Web resource for synthetic biology (sbolstandard.org). The SBPkb allows researchers to query and retrieve standard biological parts for research and use in synthetic biology. Its initial version includes all of the information about parts stored in the Registry of Standard Biological Parts (partsregistry.org). SBPkb transforms this information so that it is computable, using our semantic framework for synthetic biology parts. This framework, known as SBOL-semantic, was built as part of the Synthetic Biology Open Language (SBOL), a project of the Synthetic Biology Data Exchange Group. SBOL-semantic represents commonly used synthetic biology entities, and its purpose is to improve the distribution and exchange of descriptions of biological parts. In this paper, we describe the data, our methods for transformation to SBPkb, and finally, we demonstrate the value of our knowledgebase with a set of sample queries. We use RDF technology and SPARQL queries to retrieve candidate "promoter" parts that are known to be both negatively and positively regulated. This method provides new web based data access to perform searches for parts that are not currently possible.

  17. Analog synthetic biology.

    Science.gov (United States)

    Sarpeshkar, R

    2014-03-28

    We analyse the pros and cons of analog versus digital computation in living cells. Our analysis is based on fundamental laws of noise in gene and protein expression, which set limits on the energy, time, space, molecular count and part-count resources needed to compute at a given level of precision. We conclude that analog computation is significantly more efficient in its use of resources than deterministic digital computation even at relatively high levels of precision in the cell. Based on this analysis, we conclude that synthetic biology must use analog, collective analog, probabilistic and hybrid analog-digital computational approaches; otherwise, even relatively simple synthetic computations in cells such as addition will exceed energy and molecular-count budgets. We present schematics for efficiently representing analog DNA-protein computation in cells. Analog electronic flow in subthreshold transistors and analog molecular flux in chemical reactions obey Boltzmann exponential laws of thermodynamics and are described by astoundingly similar logarithmic electrochemical potentials. Therefore, cytomorphic circuits can help to map circuit designs between electronic and biochemical domains. We review recent work that uses positive-feedback linearization circuits to architect wide-dynamic-range logarithmic analog computation in Escherichia coli using three transcription factors, nearly two orders of magnitude more efficient in parts than prior digital implementations.

  18. 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.

  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. Branching processes in biology

    CERN Document Server

    Kimmel, Marek

    2015-01-01

    This book provides a theoretical background of branching processes and discusses their biological applications. Branching processes are a well-developed and powerful set of tools in the field of applied probability. The range of applications considered includes molecular biology, cellular biology, human evolution and medicine. The branching processes discussed include Galton-Watson, Markov, Bellman-Harris, Multitype, and General Processes. As an aid to understanding specific examples, two introductory chapters, and two glossaries are included that provide background material in mathematics and in biology. The book will be of interest to scientists who work in quantitative modeling of biological systems, particularly probabilists, mathematical biologists, biostatisticians, cell biologists, molecular biologists, and bioinformaticians. The authors are a mathematician and cell biologist who have collaborated for more than a decade in the field of branching processes in biology for this new edition. This second ex...

  1. Biological detector and method

    Science.gov (United States)

    Sillerud, Laurel; Alam, Todd M; McDowell, Andrew F

    2013-02-26

    A biological detector includes a conduit for receiving a fluid containing one or more magnetic nanoparticle-labeled, biological objects to be detected and one or more permanent magnets or electromagnet for establishing a low magnetic field in which the conduit is disposed. A microcoil is disposed proximate the conduit for energization at a frequency that permits detection by NMR spectroscopy of whether the one or more magnetically-labeled biological objects is/are present in the fluid.

  2. Space Synthetic Biology (SSB)

    Data.gov (United States)

    National Aeronautics and Space Administration — This project focused on employing advanced biological engineering and bioelectrochemical reactor systems to increase life support loop closure and in situ resource...

  3. Biological Water Quality Criteria

    Science.gov (United States)

    Page contains links to Technical Documents pertaining to Biological Water Quality Criteria, including, technical assistance documents for states, tribes and territories, program overviews, and case studies.

  4. The Tipping Point: Biological Terrorism

    Directory of Open Access Journals (Sweden)

    Scott Cary

    2009-01-01

    Full Text Available This article presents a strategic, operational, and tactical analysis of information currently available on the state of bio-weapons development by non-state actors, primarily Islamist jihadists. It discusses the evidence supporting a practical assessment that non-state actors have begun to acquire, and in the near-term intend to employ, bio-weapons. A pathogen and method of attack specifically designed to achieve the strategic goals of jihadists are presented as functional examples of the problem of the emerging global bio-weapons threat.Is a terrorist attack utilizing biological weapons a real threat? If so, is there a way to predict the circumstances under which it might happen or how it might be conducted? This article explores what is known and cannot be known about these questions, and will examine the threat of biological terrorism in the context of the strategic goals, operational methods, and tactical intentions of Islamist terrorists.

  5. Systems Biology of the Fluxome

    Directory of Open Access Journals (Sweden)

    Miguel A. Aon

    2015-07-01

    Full Text Available The advent of high throughput -omics has made the accumulation of comprehensive data sets possible, consisting of changes in genes, transcripts, proteins and metabolites. Systems biology-inspired computational methods for translating metabolomics data into fluxomics provide a direct functional, dynamic readout of metabolic networks. When combined with appropriate experimental design, these methods deliver insightful knowledge about cellular function under diverse conditions. The use of computational models accounting for detailed kinetics and regulatory mechanisms allow us to unravel the control and regulatory properties of the fluxome under steady and time-dependent behaviors. This approach extends the analysis of complex systems from description to prediction, including control of complex dynamic behavior ranging from biological rhythms to catastrophic lethal arrhythmias. The powerful quantitative metabolomics-fluxomics approach will help our ability to engineer unicellular and multicellular organisms evolve from trial-and-error to a more predictable process, and from cells to organ and organisms.

  6. Workshop Introduction: Systems Biology and Biological Models

    Science.gov (United States)

    As we consider the future of toxicity testing, the importance of applying biological models to this problem is clear. Modeling efforts exist along a continuum with respect to the level of organization (e.g. cell, tissue, organism) linked to the resolution of the model. Generally,...

  7. Publishing activities improves undergraduate biology education.

    Science.gov (United States)

    Smith, Michelle K

    2018-06-01

    To improve undergraduate biology education, there is an urgent need for biology instructors to publish their innovative active-learning instructional materials in peer-reviewed journals. To do this, instructors can measure student knowledge about a variety of biology concepts, iteratively design activities, explore student learning outcomes and publish the results. Creating a set of well-vetted activities, searchable through a journal interface, saves other instructors time and encourages the use of active-learning instructional practices. For authors, these publications offer new opportunities to collaborate and can provide evidence of a commitment to using active-learning instructional techniques in the classroom.

  8. Transformation of ammonia i biological airfilters

    DEFF Research Database (Denmark)

    Nielsen, Lars Peter; Sørensen, Karen; Andersen, Mathias

    2007-01-01

    Ammonia is a major compound in ventilation air from animal houses. In biological filters it is with varying efficiency transformed by physical, biological, and chemical processes and ends up as ammonium, nitrate, and nitrite dissolved in water and as dinitrogen, nitrous oxide and nitric oxide...... emitted to the air. To identify the key regulators of these transformations we have combined data from studies of microbiology and performance in 10 experimental and full scale filters of varying design, loading, and management. Inhibition by nitrite controlled ammonium oxidation and pH, while biological...... removal without too much energy consumption, waste water production, green house gas emission, or suppression of the filters odor removal efficiency....

  9. Design Methodology - Design Synthesis

    DEFF Research Database (Denmark)

    Andreasen, Mogens Myrup

    2003-01-01

    Design Methodology is part of our practice and our knowledge about designing, and it has been strongly supported by the establishing and work of a design research community. The aim of this article is to broaden the reader¿s view of designing and Design Methodology. This is done by sketching...... the development of Design Methodology through time and sketching some important approaches and methods. The development is mainly forced by changing industrial condition, by the growth of IT support for designing, but also by the growth of insight into designing created by design researchers.......ABSTRACT Design Methodology shall be seen as our understanding of how to design; it is an early (emerging late 60ies) and original articulation of teachable and learnable methodics. The insight is based upon two sources: the nature of the designed artefacts and the nature of human designing. Today...

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

    Science.gov (United States)

    Fletcher, Eugene; Krivoruchko, Anastasia; Nielsen, Jens

    2016-06-01

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

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

    DEFF Research Database (Denmark)

    Fletcher, Eugene; Krivoruchko, Anastasia; Nielsen, Jens

    2016-01-01

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

  12. 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.

  13. 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).

  14. Advances in radiation biology

    International Nuclear Information System (INIS)

    Lett, J.T.; Ehmann, U.K.; Cox, A.B.

    1987-01-01

    The classical period of radiation biology is coming to a close. Such change always occurs at a time when the ideas and concepts that promoted the burgeoning of an infant science are no longer adequate. This volume covers a number of areas in which new ideas and research are playing a vital role, including cellular radiation sensitivity, radioactive waste disposal, and space radiation biology

  15. Physics and biology

    International Nuclear Information System (INIS)

    Frauenfelder, H.

    1988-01-01

    The author points out that the coupling between physics and biology is becoming closer as time goes on. He tries to show that physical studies on biological systems not only yield insight into biology but also provide results of interest to physics. Biological systems are extremly complex system. Ideally one would like to understand the behavior of such systems in terms of the behavior of its constituent atoms. Since in small organisms this may be 10 20 atoms, it is clear these are not simple many-body systems. He reviews the basic elements of cells and then considers the broader questions of structure, complexity, and function, which must be looked at on levels from the cell to the organism. Despite the vast amount of observational material already in existence, biophysics and biological physics are only at a beginning. We can expect that physics will continue to interact strongly with biology. Actually, the connection also includes chemistry and mathematics. New tools that become available in physics will continue to be applied to biological problems. We can expect that the flow of information will not be one way; biological systems will provide new information on many old and new parts of physics, from reaction theory and transport phenomena to complexity, cooperativity, and nonlinear processes

  16. Psoriasis : implications of biologics

    NARCIS (Netherlands)

    Lecluse, L.L.A.

    2010-01-01

    Since the end of 2004 several specific immunomodulating therapies: ‘biologic response modifiers’ or ‘biologics’ have been registered for moderate to severe psoriasis in Europe. This thesis is considering the implications of the introduction of the biologics for psoriasis patients, focusing on safety

  17. Tropical Freshwater Biology

    African Journals Online (AJOL)

    Tropical Freshwater Biology promotes the publication of scientific contributions in the field of freshwater biology in the tropical and subtropical regions of the world. One issue is published annually but this number may be increased. Original research papers and short communications on any aspect of tropical freshwater ...

  18. Multiscale Biological Materials

    DEFF Research Database (Denmark)

    Frølich, Simon

    of multiscale biological systems have been investigated and new research methods for automated Rietveld refinement and diffraction scattering computed tomography developed. The composite nature of biological materials was investigated at the atomic scale by looking at the consequences of interactions between...

  19. Integrated Biological Control

    International Nuclear Information System (INIS)

    JOHNSON, A.R.

    2002-01-01

    Biological control is any activity taken to prevent, limit, clean up, or remediate potential environmental, health and safety, or workplace quality impacts from plants, animals, or microorganisms. At Hanford the principal emphasis of biological control is to prevent the transport of radioactive contamination by biological vectors (plants, animals, or microorganisms), and where necessary, control and clean up resulting contamination. Other aspects of biological control at Hanford include industrial weed control (e.g.; tumbleweeds), noxious weed control (invasive, non-native plant species), and pest control (undesirable animals such as rodents and stinging insects; and microorganisms such as molds that adversely affect the quality of the workplace environment). Biological control activities may be either preventive (apriori) or in response to existing contamination spread (aposteriori). Surveillance activities, including ground, vegetation, flying insect, and other surveys, and apriori control actions, such as herbicide spraying and placing biological barriers, are important in preventing radioactive contamination spread. If surveillance discovers that biological vectors have spread radioactive contamination, aposteriori control measures, such as fixing contamination, followed by cleanup and removal of the contamination to an approved disposal location are typical response functions. In some cases remediation following the contamination cleanup and removal is necessary. Biological control activities for industrial weeds, noxious weeds and pests have similar modes of prevention and response

  20. Designing Material Materialising Design

    DEFF Research Database (Denmark)

    Nicholas, Paul

    2013-01-01

    Designing Material Materialising Design documents five projects developed at the Centre for Information Technology and Architecture (CITA) at the Royal Danish Academy of Fine Arts, School of Architecture. These projects explore the idea that new designed materials might require new design methods....... Focusing on fibre reinforced composites, this book sustains an exploration into the design and making of elastically tailored architectural structures that rely on the use of computational design to predict sensitive interdependencies between geometry and behaviour. Developing novel concepts...

  1. Frontiers in mathematical biology

    CERN Document Server

    1994-01-01

    Volume 100, which is the final volume of the LNBM series serves to commemorate the acievements in two decades of this influential collection of books in mathematical biology. The contributions, by the leading mathematical biologists, survey the state of the art in the subject, and offer speculative, philosophical and critical analyses of the key issues confronting the field. The papers address fundamental issues in cell and molecular biology, organismal biology, evolutionary biology, population ecology, community and ecosystem ecology, and applied biology, plus the explicit and implicit mathematical challenges. Cross-cuttting issues involve the problem of variation among units in nonlinear systems, and the related problems of the interactions among phenomena across scales of space, time and organizational complexity.

  2. Biological sample collector

    Science.gov (United States)

    Murphy, Gloria A [French Camp, CA

    2010-09-07

    A biological sample collector is adapted to a collect several biological samples in a plurality of filter wells. A biological sample collector may comprise a manifold plate for mounting a filter plate thereon, the filter plate having a plurality of filter wells therein; a hollow slider for engaging and positioning a tube that slides therethrough; and a slide case within which the hollow slider travels to allow the tube to be aligned with a selected filter well of the plurality of filter wells, wherein when the tube is aligned with the selected filter well, the tube is pushed through the hollow slider and into the selected filter well to sealingly engage the selected filter well and to allow the tube to deposit a biological sample onto a filter in the bottom of the selected filter well. The biological sample collector may be portable.

  3. Space biology research development

    Science.gov (United States)

    Bonting, Sjoerd L.

    1993-01-01

    The purpose of the Search for Extraterrestrial Intelligence (SETI) Institute is to conduct and promote research related activities regarding the search for extraterrestrial life, particularly intelligent life. Such research encompasses the broad discipline of 'Life in the Universe', including all scientific and technological aspects of astronomy and the planetary sciences, chemical evolution, the origin of life, biological evolution, and cultural evolution. The primary purpose was to provide funding for the Principal Investigator to collaborate with the personnel of the SETI Institute and the NASA-Ames Research center in order to plan and develop space biology research on and in connection with Space Station Freedom; to promote cooperation with the international partners in the space station; to conduct a study on the use of biosensors in space biology research and life support system operation; and to promote space biology research through the initiation of an annual publication 'Advances in Space Biology and Medicine'.

  4. Pembangunan Kebun Biologi Wamena*[establishment of Wamena Biological Gardens

    OpenAIRE

    Rahmansyah, M; Latupapua, HJD

    2003-01-01

    The richness of biological resources (biodiversity) in mountainous area of Papua is an asset that has to be preserved.Exploitation of natural resources often cause damage on those biological assets and as genetic resources.Care has to be taken to overcome the situation of biological degradation, and alternate steps had been shaped on ex-situ biological conservation. Wamena Biological Gardens, as an ex-situ biological conservation, has been established to keep the high mountain biological and ...

  5. New Approaches in Cancer Biology Can Inform the Biology Curriculum.

    Science.gov (United States)

    Jones, Lynda; Gordon, Diana; Zelinski, Mary

    2018-03-01

    Students tend to be very interested in medical issues that affect them and their friends and family. Using cancer as a hook, the ART of Reproductive Medicine: Oncofertility curriculum (free, online, and NIH sponsored) has been developed to supplement the teaching of basic biological concepts and to connect biology and biomedical research. This approach allows integration of up-to-date information on cancer and cancer treatment, cell division, male and female reproductive anatomy and physiology, cryopreservation, fertility preservation, stem cells, ethics, and epigenetics into an existing biology curriculum. Many of the topics covered in the curriculum relate to other scientific disciplines, such as the latest developments in stem cell research including tissue bioengineering and gene therapy for inherited mitochondrial disease, how epigenetics occurs chemically to affect gene expression or suppression and how it can be passed down through the generations, and the variety of biomedical careers students could pursue. The labs are designed to be open-ended and inquiry-based, and extensions to the experiments are provided so that students can explore questions further. Case studies and ethical dilemmas are provided to encourage thoughtful discussion. In addition, each chapter of the curriculum includes links to scientific papers, additional resources on each topic, and NGSS alignment.

  6. Production of a biological surfactant

    Directory of Open Access Journals (Sweden)

    N. Gladys Rosero

    2002-01-01

    Full Text Available This paper summarizes the scale up work performed at the Colombian Petroleum Institute on a process to produce at pilot plant level a biosurfactant of the rhamnolipid type. By examination of both the activation conditions of the microorganism and design aspects of the broth, a stable condition was achieved which consistently triggers the production mechanisms and thus it was obtained a significant increment in biosurfactant productivity. The biological surfactant exhibited high efficiency in applications such as hydrocarbon biodegradation in saline environments, corrosion inhibition, and crude oil recovery from storage tank bottom sludges.

  7. Anthropic principle in biology and radiation biology

    International Nuclear Information System (INIS)

    Akif'ev, A. P.; Degtyarev, S.V.

    1999-01-01

    It was suggested to add the anthropic principle of the Universe according to which the physical constants of fundamental particles of matter and the laws of their counteraction are those that an appearance of man and mind becomes possible and necessary, with some biological constants to the set of fundamental constants. With reparation of DNA as an example it was shown how a cell ran some parameters of Watson-Crick double helix. It was pointed that the concept of the anthropic principle of the Universe in its full body including biological constants was a key to developing of a unified theory of evolution of the Universe within the limits of scientific creationism [ru

  8. Biology Today. Thinking Chemically about Biology.

    Science.gov (United States)

    Flannery, Maura C.

    1990-01-01

    Discussed are applications of biochemistry. Included are designed drugs, clever drugs, carcinogenic structures, sugary wine, caged chemicals, biomaterials, marine chemistry, biopolymers, prospecting bacteria, and plant chemistry. (CW)

  9. Managing biological diversity

    Science.gov (United States)

    Samson, Fred B.; Knopf, Fritz L.

    1993-01-01

    Biological diversity is the variety of life and accompanying ecological processes (Off. Technol. Assess. 1987, Wilcove and Samson 1987, Keystone 1991). Conservation of biological diversity is a major environmental issue (Wilson 1988, Counc. Environ. Quality 1991). The health and future of the earth's ecological systems (Lubchenco et al. 1991), global climate change (Botkin 1990), and an ever-increasing rate in loss of species, communities, and ecological systems (Myers 1990) are among issues drawing biological diversity to the mainstream of conservation worldwide (Int. Union Conserv. Nat. and Nat. Resour. [IUCN] et al. 1991). The legal mandate for conserving biological diversity is now in place (Carlson 1988, Doremus 1991). More than 19 federal laws govern the use of biological resources in the United States (Rein 1991). The proposed National Biological Diversity Conservation and Environmental Research Act (H.R. 585 and S.58) notes the need for a national biological diversity policy, would create a national center for biological diversity research, and recommends a federal interagency strategy for ecosystem conservation. There are, however, hard choices ahead for the conservation of biological diversity, and biologists are grappling with how to set priorities in research and management (Roberts 1988). We sense disillusion among field biologists and managers relative to how to operationally approach the seemingly overwhelming charge of conserving biological diversity. Biologists also need to respond to critics like Hunt (1991) who suggest a tree farm has more biological diversity than an equal area of old-growth forest. At present, science has played only a minor role in the conservation of biological diversity (Weston 1992) with no unified approach available to evaluate strategies and programs that address the quality and quantity of biological diversity (Murphy 1990, Erwin 1992). Although actions to conserve biological diversity need to be clearly defined by

  10. A timeless biology.

    Science.gov (United States)

    Tozzi, Arturo; Peters, James F; Chafin, Clifford; De Falco, Domenico; Torday, John S

    2018-05-01

    Contrary to claims that physics is timeless while biology is time-dependent, we take the opposite standpoint: physical systems' dynamics are constrained by the arrow of time, while living assemblies are time-independent. Indeed, the concepts of "constraints" and "displacements" shed new light on the role of continuous time flow in life evolution, allowing us to sketch a physical gauge theory for biological systems in long timescales. In the very short timescales of biological systems' individual lives, time looks like "frozen" and "fixed", so that the second law of thermodynamics is momentarily wrecked. The global symmetries (standing for biological constrained trajectories, i.e. the energetic gradient flows dictated by the second law of thermodynamics in long timescales) are broken by local "displacements" where time is held constant, i.e., modifications occurring in living systems. Such displacements stand for brief local forces, able to temporarily "break" the cosmic increase in entropy. The force able to restore the symmetries (called "gauge field") stands for the very long timescales of biological evolution. Therefore, at the very low speeds of life evolution, time is no longer one of the four phase space coordinates of a spacetime Universe: it becomes just a gauge field superimposed to three-dimensional biological systems. We discuss the implications in biology: when assessing living beings, the underrated role of isolated "spatial" modifications needs to be emphasized, living apart the evolutionary role of time. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Measurement Frontiers in Molecular Biology

    Science.gov (United States)

    Laderman, Stephen

    2009-03-01

    Developments of molecular measurements and manipulations have long enabled forefront research in evolution, genetics, biological development and its dysfunction, and the impact of external factors on the behavior of cells. Measurement remains at the heart of exciting and challenging basic and applied problems in molecular and cell biology. Methods to precisely determine the identity and abundance of particular molecules amongst a complex mixture of similar and dissimilar types require the successful design and integration of multiple steps involving biochemical manipulations, separations, physical probing, and data processing. Accordingly, today's most powerful methods for characterizing life at the molecular level depend on coordinated advances in applied physics, biochemistry, chemistry, computer science, and engineering. This is well illustrated by recent approaches to the measurement of DNA, RNA, proteins, and intact cells. Such successes underlie well founded visions of how molecular biology can further assist in answering compelling scientific questions and in enabling the development of remarkable advances in human health. These visions, in turn, are motivating the interdisciplinary creation of even more comprehensive measurements. As a further and closely related consequence, they are motivating innovations in the conceptual and practical approaches to organizing and visualizing large, complex sets of interrelated experimental results and distilling from those data compelling, informative conclusions.

  12. Neutron in biology

    Energy Technology Data Exchange (ETDEWEB)

    Niimura, Nobuo [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1997-11-01

    Neutron in biology can provide an experimental method of directly locating relationship of proteins and DNA. However, there are relatively few experimental study of such objects since it takes a lot of time to collect a sufficient number of Bragg reflections and inelastic spectra due to the low flux of neutron illuminating the sample. Since a next generation neutron source of JAERI will be 5MW spallation neutron source and its effective neutron flux will be 10{sup 2} to 10{sup 3} times higher than the one of JRR-3M, neutron in biology will open a completely new world for structural biology. (author)

  13. Neutron in biology

    International Nuclear Information System (INIS)

    Niimura, Nobuo

    1997-01-01

    Neutron in biology can provide an experimental method of directly locating relationship of proteins and DNA. However, there are relatively few experimental study of such objects since it takes a lot of time to collect a sufficient number of Bragg reflections and inelastic spectra due to the low flux of neutron illuminating the sample. Since a next generation neutron source of JAERI will be 5MW spallation neutron source and its effective neutron flux will be 10 2 to 10 3 times higher than the one of JRR-3M, neutron in biology will open a completely new world for structural biology. (author)

  14. Biologically-inspired soft exosuit.

    Science.gov (United States)

    Asbeck, Alan T; Dyer, Robert J; Larusson, Arnar F; Walsh, Conor J

    2013-06-01

    In this paper, we present the design and evaluation of a novel soft cable-driven exosuit that can apply forces to the body to assist walking. Unlike traditional exoskeletons which contain rigid framing elements, the soft exosuit is worn like clothing, yet can generate moments at the ankle and hip with magnitudes of 18% and 30% of those naturally generated by the body during walking, respectively. Our design uses geared motors to pull on Bowden cables connected to the suit near the ankle. The suit has the advantages over a traditional exoskeleton in that the wearer's joints are unconstrained by external rigid structures, and the worn part of the suit is extremely light, which minimizes the suit's unintentional interference with the body's natural biomechanics. However, a soft suit presents challenges related to actuation force transfer and control, since the body is compliant and cannot support large pressures comfortably. We discuss the design of the suit and actuation system, including principles by which soft suits can transfer force to the body effectively and the biological inspiration for the design. For a soft exosuit, an important design parameter is the combined effective stiffness of the suit and its interface to the wearer. We characterize the exosuit's effective stiffness, and present preliminary results from it generating assistive torques to a subject during walking. We envision such an exosuit having broad applicability for assisting healthy individuals as well as those with muscle weakness.

  15. Establishing elements of a synthetic biology platform for Vaccinia virus production: BioBrick™ design, serum-free virus production and microcarrier-based cultivation of CV-1 cells.

    Science.gov (United States)

    Liu, Shuchang; Ruban, Ludmila; Wang, Yaohe; Zhou, Yuhong; Nesbeth, Darren N

    2017-02-01

    Vaccinia virus (VACV) is an established vector for vaccination and is beginning to prove effective as an oncolytic agent. Industrial production of VACV stands to benefit in future from advances made by synthetic biology in genome engineering and standardisation. The CV-1 cell line can be used for VACV propagation and has been used extensively with the CRISPR/Cas9 system for making precise edits of the VACV genome. Here we take first steps toward establishing a scalable synthetic biology platform for VACV production with CV-1 cells featuring standardised biological tools and serum free cell cultivation. We propose a new BioBrick™ plasmid backbone format for inserting transgenes into VACV. We then test the performance of CV-1 cells in propagation of a conventional recombinant Lister strain VACV, VACVL-15 RFP, in a serum-free process. CV-1 cells grown in 5% foetal bovine serum (FBS) Dulbecco's Modified Eagle Medium (DMEM) were adapted to growth in OptiPRO and VP-SFM brands of serum-free media. Specific growth rates of 0.047 h -1 and 0.044 h -1 were observed for cells adapted to OptiPRO and VP-SFM respectively, compared to 0.035 h -1 in 5% FBS DMEM. Cells adapted to OptiPRO and to 5% FBS DMEM achieved recovery ratios of over 96%, an indication of their robustness to cryopreservation. Cells adapted to VP-SFM showed a recovery ratio of 82%. Virus productivity in static culture, measured as plaque forming units (PFU) per propagator cell, was 75 PFU/cell for cells in 5% FBS DMEM. VP-SFM and OptiPRO adaptation increased VACV production to 150 PFU/cell and 350 PFU/cell respectively. Boosted PFU/cell from OptiPRO-adapted cells persisted when 5% FBS DMEM or OptiPRO medium was observed during the infection step and when titre was measured using cells adapted to 5% FBS DMEM or OptiPRO medium. Finally, OptiPRO-adapted CV-1 cells were successfully cultivated using Cytodex-1 microcarriers to inform future scale up studies.

  16. Establishing elements of a synthetic biology platform for Vaccinia virus production: BioBrick™ design, serum-free virus production and microcarrier-based cultivation of CV-1 cells

    Directory of Open Access Journals (Sweden)

    Shuchang Liu

    2017-02-01

    Full Text Available Vaccinia virus (VACV is an established vector for vaccination and is beginning to prove effective as an oncolytic agent. Industrial production of VACV stands to benefit in future from advances made by synthetic biology in genome engineering and standardisation. The CV-1 cell line can be used for VACV propagation and has been used extensively with the CRISPR/Cas9 system for making precise edits of the VACV genome. Here we take first steps toward establishing a scalable synthetic biology platform for VACV production with CV-1 cells featuring standardised biological tools and serum free cell cultivation. We propose a new BioBrick™ plasmid backbone format for inserting transgenes into VACV. We then test the performance of CV-1 cells in propagation of a conventional recombinant Lister strain VACV, VACVL-15 RFP, in a serum-free process. CV-1 cells grown in 5% foetal bovine serum (FBS Dulbecco’s Modified Eagle Medium (DMEM were adapted to growth in OptiPRO and VP-SFM brands of serum-free media. Specific growth rates of 0.047 h−1 and 0.044 h−1 were observed for cells adapted to OptiPRO and VP-SFM respectively, compared to 0.035 h−1 in 5% FBS DMEM. Cells adapted to OptiPRO and to 5% FBS DMEM achieved recovery ratios of over 96%, an indication of their robustness to cryopreservation. Cells adapted to VP-SFM showed a recovery ratio of 82%. Virus productivity in static culture, measured as plaque forming units (PFU per propagator cell, was 75 PFU/cell for cells in 5% FBS DMEM. VP-SFM and OptiPRO adaptation increased VACV production to 150 PFU/cell and 350 PFU/cell respectively. Boosted PFU/cell from OptiPRO-adapted cells persisted when 5% FBS DMEM or OptiPRO medium was observed during the infection step and when titre was measured using cells adapted to 5% FBS DMEM or OptiPRO medium. Finally, OptiPRO-adapted CV-1 cells were successfully cultivated using Cytodex-1 microcarriers to inform future scale up studies.

  17. Mechanical Biological Treatment

    DEFF Research Database (Denmark)

    Bilitewski, B-; Oros, Christiane; Christensen, Thomas Højlund

    2011-01-01

    The basic processes and technologies of composting and anaerobic digestion, as described in the previous chapters, are usually used for specific or source-separated organic waste flows. However, in the 1990s mechanical biological waste treatment technologies (MBT) were developed for unsorted...... or residual waste (after some recyclables removed at the source). The concept was originally to reduce the amount of waste going to landfill, but MBT technologies are today also seen as plants recovering fuel as well as material fractions. As the name suggests the technology combines mechanical treatment...... technologies (screens, sieves, magnets, etc.) with biological technologies (composting, anaerobic digestion). Two main technologies are available: Mechanical biological pretreatment (MBP), which first removes an RDF fraction and then biologically treats the remaining waste before most of it is landfilled...

  18. Nutritional Systems Biology

    DEFF Research Database (Denmark)

    Jensen, Kasper

    and network biology has the potential to increase our understanding of how small molecules affect metabolic pathways and homeostasis, how this perturbation changes at the disease state, and to what extent individual genotypes contribute to this. A fruitful strategy in approaching and exploring the field...... biology research. The paper also shows as a proof-of-concept that a systems biology approach to diet is meaningful and demonstrates some basic principles on how to work with diet systematic. The second chapter of this thesis we developed the resource NutriChem v1.0. A foodchemical database linking...... sites of diet on the disease pathway. We propose a framework for interrogating the critical targets in colon cancer process and identifying plant-based dietary interventions as important modifiers using a systems chemical biology approach. The fifth chapter of the thesis is on discovering of novel anti...

  19. Neutron dosimetry in biology

    International Nuclear Information System (INIS)

    Sigurbjoernsson, B.; Smith, H.H.; Gustafsson, A.

    1965-01-01

    To study adequately the biological effects of different energy neutrons it is necessary to have high-intensity sources which are not contaminated by other radiations, the most serious of which are gamma rays. An effective dosimetry must provide an accurate measure of the absorbed dose, in biological materials, of each type of radiation at any reactor facility involved in radiobiological research. A standardized biological dosimetry, in addition to physical and chemical methods, may be desirable. The ideal data needed to achieve a fully documented dosimetry has been compiled by H. Glubrecht: (1) Energy spectrum and intensity of neutrons; (2) Angular distribution of neutrons on the whole surface of the irradiated object; (3) Additional undesired radiation accompanying the neutrons; (4) Physical state and chemical composition of the irradiated object. It is not sufficient to note only an integral dose value (e.g. in 'rad') as the biological effect depends on the above data

  20. Hammond Bay Biological Station

    Data.gov (United States)

    Federal Laboratory Consortium — Hammond Bay Biological Station (HBBS), located near Millersburg, Michigan, is a field station of the USGS Great Lakes Science Center (GLSC). HBBS was established by...