On the Cut-off Point for Combinatorial Group Testing

DEFF Research Database (Denmark)

Fischer, Paul; Klasner, N.; Wegener, I.

1999-01-01

is answered by 1 if Q contains at least one essential object and by 0 otherwise. In the statistical setting the objects are essential, independently of each other, with a given probability p combinatorial setting the number k ... group testing is equal to p* = 12(3 - 5), i.e., the strategy of testing each object individually minimizes the average number of queries iff p >= p* or n = 1. In the combinatorial setting the worst case number of queries is of interest. It has been conjectured that the cut-off point of combinatorial...

Systematic identification of combinatorial drivers and targets in cancer cell lines.

Directory of Open Access Journals (Sweden)

Adel Tabchy

Full Text Available There is an urgent need to elicit and validate highly efficacious targets for combinatorial intervention from large scale ongoing molecular characterization efforts of tumors. We established an in silico bioinformatic platform in concert with a high throughput screening platform evaluating 37 novel targeted agents in 669 extensively characterized cancer cell lines reflecting the genomic and tissue-type diversity of human cancers, to systematically identify combinatorial biomarkers of response and co-actionable targets in cancer. Genomic biomarkers discovered in a 141 cell line training set were validated in an independent 359 cell line test set. We identified co-occurring and mutually exclusive genomic events that represent potential drivers and combinatorial targets in cancer. We demonstrate multiple cooperating genomic events that predict sensitivity to drug intervention independent of tumor lineage. The coupling of scalable in silico and biologic high throughput cancer cell line platforms for the identification of co-events in cancer delivers rational combinatorial targets for synthetic lethal approaches with a high potential to pre-empt the emergence of resistance.

Systematic identification of combinatorial drivers and targets in cancer cell lines.

Science.gov (United States)

Tabchy, Adel; Eltonsy, Nevine; Housman, David E; Mills, Gordon B

2013-01-01

There is an urgent need to elicit and validate highly efficacious targets for combinatorial intervention from large scale ongoing molecular characterization efforts of tumors. We established an in silico bioinformatic platform in concert with a high throughput screening platform evaluating 37 novel targeted agents in 669 extensively characterized cancer cell lines reflecting the genomic and tissue-type diversity of human cancers, to systematically identify combinatorial biomarkers of response and co-actionable targets in cancer. Genomic biomarkers discovered in a 141 cell line training set were validated in an independent 359 cell line test set. We identified co-occurring and mutually exclusive genomic events that represent potential drivers and combinatorial targets in cancer. We demonstrate multiple cooperating genomic events that predict sensitivity to drug intervention independent of tumor lineage. The coupling of scalable in silico and biologic high throughput cancer cell line platforms for the identification of co-events in cancer delivers rational combinatorial targets for synthetic lethal approaches with a high potential to pre-empt the emergence of resistance.

Combinatorial geometry domain decomposition strategies for Monte Carlo simulations

Energy Technology Data Exchange (ETDEWEB)

Li, G.; Zhang, B.; Deng, L.; Mo, Z.; Liu, Z.; Shangguan, D.; Ma, Y.; Li, S.; Hu, Z. [Institute of Applied Physics and Computational Mathematics, Beijing, 100094 (China)

2013-07-01

Analysis and modeling of nuclear reactors can lead to memory overload for a single core processor when it comes to refined modeling. A method to solve this problem is called 'domain decomposition'. In the current work, domain decomposition algorithms for a combinatorial geometry Monte Carlo transport code are developed on the JCOGIN (J Combinatorial Geometry Monte Carlo transport INfrastructure). Tree-based decomposition and asynchronous communication of particle information between domains are described in the paper. Combination of domain decomposition and domain replication (particle parallelism) is demonstrated and compared with that of MERCURY code. A full-core reactor model is simulated to verify the domain decomposition algorithms using the Monte Carlo particle transport code JMCT (J Monte Carlo Transport Code), which has being developed on the JCOGIN infrastructure. Besides, influences of the domain decomposition algorithms to tally variances are discussed. (authors)

Combinatorial geometry domain decomposition strategies for Monte Carlo simulations

International Nuclear Information System (INIS)

Li, G.; Zhang, B.; Deng, L.; Mo, Z.; Liu, Z.; Shangguan, D.; Ma, Y.; Li, S.; Hu, Z.

2013-01-01

Analysis and modeling of nuclear reactors can lead to memory overload for a single core processor when it comes to refined modeling. A method to solve this problem is called 'domain decomposition'. In the current work, domain decomposition algorithms for a combinatorial geometry Monte Carlo transport code are developed on the JCOGIN (J Combinatorial Geometry Monte Carlo transport INfrastructure). Tree-based decomposition and asynchronous communication of particle information between domains are described in the paper. Combination of domain decomposition and domain replication (particle parallelism) is demonstrated and compared with that of MERCURY code. A full-core reactor model is simulated to verify the domain decomposition algorithms using the Monte Carlo particle transport code JMCT (J Monte Carlo Transport Code), which has being developed on the JCOGIN infrastructure. Besides, influences of the domain decomposition algorithms to tally variances are discussed. (authors)

Scaffold architecture and pharmacophoric properties of natural products and trade drugs: application in the design of natural product-based combinatorial libraries.

Science.gov (United States)

Lee, M L; Schneider, G

2001-01-01

Natural products were analyzed to determine whether they contain appealing novel scaffold architectures for potential use in combinatorial chemistry. Ring systems were extracted and clustered on the basis of structural similarity. Several such potential scaffolds for combinatorial chemistry were identified that are not present in current trade drugs. For one of these scaffolds a virtual combinatorial library was generated. Pharmacophoric properties of natural products, trade drugs, and the virtual combinatorial library were assessed using a self-organizing map. Obviously, current trade drugs and natural products have several topological pharmacophore patterns in common. These features can be systematically explored with selected combinatorial libraries based on a combination of natural product-derived and synthetic molecular building blocks.

Combinatorial pretreatment and fermentation optimization enabled a record yield on lignin bioconversion.

Science.gov (United States)

Liu, Zhi-Hua; Xie, Shangxian; Lin, Furong; Jin, Mingjie; Yuan, Joshua S

2018-01-01

Lignin valorization has recently been considered to be an essential process for sustainable and cost-effective biorefineries. Lignin represents a potential new feedstock for value-added products. Oleaginous bacteria such as Rhodococcus opacus can produce intracellular lipids from biodegradation of aromatic substrates. These lipids can be used for biofuel production, which can potentially replace petroleum-derived chemicals. However, the low reactivity of lignin produced from pretreatment and the underdeveloped fermentation technology hindered lignin bioconversion to lipids. In this study, combinatorial pretreatment with an optimized fermentation strategy was evaluated to improve lignin valorization into lipids using R. opacus PD630. As opposed to single pretreatment, combinatorial pretreatment produced a 12.8-75.6% higher lipid concentration in fermentation using lignin as the carbon source. Gas chromatography-mass spectrometry analysis showed that combinatorial pretreatment released more aromatic monomers, which could be more readily utilized by lignin-degrading strains. Three detoxification strategies were used to remove potential inhibitors produced from pretreatment. After heating detoxification of the lignin stream, the lipid concentration further increased by 2.9-9.7%. Different fermentation strategies were evaluated in scale-up lipid fermentation using a 2.0-l fermenter. With laccase treatment of the lignin stream produced from combinatorial pretreatment, the highest cell dry weight and lipid concentration were 10.1 and 1.83 g/l, respectively, in fed-batch fermentation, with a total soluble substrate concentration of 40 g/l. The improvement of the lipid fermentation performance may have resulted from lignin depolymerization by the combinatorial pretreatment and laccase treatment, reduced inhibition effects by fed-batch fermentation, adequate oxygen supply, and an accurate pH control in the fermenter. Overall, these results demonstrate that combinatorial

Synthetic Strategies for High Dielectric Constant Silicone Elastomers

DEFF Research Database (Denmark)

Madsen, Frederikke Bahrt

synthetic strategies were developed in this Ph.D. thesis, in order to create silicone elastomers with high dielectric constants and thereby higher energy densities. The work focused on maintaining important properties such as dielectric loss, electrical breakdown strength and elastic modulus....... The methodology therefore involved chemically grafting high dielectric constant chemical groups onto the elastomer network, as this would potentially provide a stable elastomer system upon continued activation of the material. The first synthetic strategy involved the synthesis of a new type of cross...... extender’ that allowed for chemical modifications such as Cu- AAC. This route was promising for one-pot elastomer preparation and as a high dielectric constant additive to commercial silicone systems. The second approach used the borane-catalysed Piers-Rubinsztajn reaction to form spatially well...

Recent advances in combinatorial biosynthesis for drug discovery

Directory of Open Access Journals (Sweden)

Sun H

2015-02-01

Full Text Available Huihua Sun,1,* Zihe Liu,1,* Huimin Zhao,1,2 Ee Lui Ang1 1Metabolic Engineering Research Laboratory, Institute of Chemical and Engineering Sciences, Agency for Science, Technology and Research, Singapore; 2Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA *These authors contributed equally to this work Abstract: Because of extraordinary structural diversity and broad biological activities, natural products have played a significant role in drug discovery. These therapeutically important secondary metabolites are assembled and modified by dedicated biosynthetic pathways in their host living organisms. Traditionally, chemists have attempted to synthesize natural product analogs that are important sources of new drugs. However, the extraordinary structural complexity of natural products sometimes makes it challenging for traditional chemical synthesis, which usually involves multiple steps, harsh conditions, toxic organic solvents, and byproduct wastes. In contrast, combinatorial biosynthesis exploits substrate promiscuity and employs engineered enzymes and pathways to produce novel “unnatural” natural products, substantially expanding the structural diversity of natural products with potential pharmaceutical value. Thus, combinatorial biosynthesis provides an environmentally friendly way to produce natural product analogs. Efficient expression of the combinatorial biosynthetic pathway in genetically tractable heterologous hosts can increase the titer of the compound, eventually resulting in less expensive drugs. In this review, we will discuss three major strategies for combinatorial biosynthesis: 1 precursor-directed biosynthesis; 2 enzyme-level modification, which includes swapping of the entire domains, modules and subunits, site-specific mutagenesis, and directed evolution; 3 pathway-level recombination. Recent examples of combinatorial biosynthesis employing these

Applications of combinatorial optimization

CERN Document Server

Paschos, Vangelis Th

2013-01-01

Combinatorial optimization is a multidisciplinary scientific area, lying in the interface of three major scientific domains: mathematics, theoretical computer science and management. The three volumes of the Combinatorial Optimization series aims to cover a wide range of topics in this area. These topics also deal with fundamental notions and approaches as with several classical applications of combinatorial optimization. "Applications of Combinatorial Optimization" is presenting a certain number among the most common and well-known applications of Combinatorial Optimization.

Concepts of combinatorial optimization

CERN Document Server

Paschos, Vangelis Th

2014-01-01

Combinatorial optimization is a multidisciplinary scientific area, lying in the interface of three major scientific domains: mathematics, theoretical computer science and management.  The three volumes of the Combinatorial Optimization series aim to cover a wide range  of topics in this area. These topics also deal with fundamental notions and approaches as with several classical applications of combinatorial optimization.Concepts of Combinatorial Optimization, is divided into three parts:- On the complexity of combinatorial optimization problems, presenting basics about worst-case and randomi

Effect of the Implicit Combinatorial Model on Combinatorial Reasoning in Secondary School Pupils.

Science.gov (United States)

Batanero, Carmen; And Others

1997-01-01

Elementary combinatorial problems may be classified into three different combinatorial models: (1) selection; (2) partition; and (3) distribution. The main goal of this research was to determine the effect of the implicit combinatorial model on pupils' combinatorial reasoning before and after instruction. Gives an analysis of variance of the…

Enabling techniques in the search for new antibiotics: Combinatorial biosynthesis of sugar-containing antibiotics.

Science.gov (United States)

Park, Je Won; Nam, Sang-Jip; Yoon, Yeo Joon

2017-06-15

Nature has a talent for inventing a vast number of natural products, including hybrids generated by blending different scaffolds, resulting in a myriad of bioactive chemical entities. Herein, we review the highlights and recent trends (2010-2016) in the combinatorial biosynthesis of sugar-containing antibiotics where nature's structural diversification capabilities are exploited to enable the creation of new anti-infective and anti-proliferative drugs. In this review, we describe the modern combinatorial biosynthetic approaches for polyketide synthase-derived complex and aromatic polyketides, non-ribosomal peptide synthetase-directed lipo-/glycopeptides, aminoglycosides, nucleoside antibiotics, and alkaloids, along with their therapeutic potential. Finally, we present the feasible nexus between combinatorial biosynthesis, systems biology, and synthetic biology as a toolbox to provide new antibiotics that will be indispensable in the post-antibiotic era. Copyright © 2016 Elsevier Inc. All rights reserved.

Combinatorial application of two aldehyde oxidoreductases on isobutanol production in the presence of furfural.

Science.gov (United States)

Seo, Hyung-Min; Jeon, Jong-Min; Lee, Ju Hee; Song, Hun-Suk; Joo, Han-Byul; Park, Sung-Hee; Choi, Kwon-Young; Kim, Yong Hyun; Park, Kyungmoon; Ahn, Jungoh; Lee, Hongweon; Yang, Yung-Hun

2016-01-01

Furfural is a toxic by-product formulated from pretreatment processes of lignocellulosic biomass. In order to utilize the lignocellulosic biomass on isobutanol production, inhibitory effect of the furfural on isobutanol production was investigated and combinatorial application of two oxidoreductases, FucO and YqhD, was suggested as an alternative strategy. Furfural decreased cell growth and isobutanol production when only YqhD or FucO was employed as an isobutyraldehyde oxidoreductase. However, combinatorial overexpression of FucO and YqhD could overcome the inhibitory effect of furfural giving higher isobutanol production by 110% compared with overexpression of YqhD. The combinatorial oxidoreductases increased furfural detoxification rate 2.1-fold and also accelerated glucose consumption 1.4-fold. When it compares to another known system increasing furfural tolerance, membrane-bound transhydrogenase (pntAB), the combinatorial aldehyde oxidoreductases were better on cell growth and production. Thus, to control oxidoreductases is important to produce isobutanol using furfural-containing biomass and the combinatorial overexpression of FucO and YqhD can be an alternative strategy.

Combinatorial biosynthesis of sapogenins and saponins in Saccharomyces cerevisiae using a C-16α hydroxylase from Bupleurum falcatum

Science.gov (United States)

Moses, Tessa; Pollier, Jacob; Almagro, Lorena; Buyst, Dieter; Van Montagu, Marc; Pedreño, María A.; Martins, José C.; Thevelein, Johan M.; Goossens, Alain

2014-01-01

The saikosaponins comprise oleanane- and ursane-type triterpene saponins that are abundantly present in the roots of the genus Bupleurum widely used in Asian traditional medicine. Here we identified a gene, designated CYP716Y1, encoding a cytochrome P450 monooxygenase from Bupleurum falcatum that catalyzes the C-16α hydroxylation of oleanane- and ursane-type triterpenes. Exploiting this hitherto unavailable enzymatic activity, we launched a combinatorial synthetic biology program in which we combined CYP716Y1 with oxidosqualene cyclase, P450, and glycosyltransferase genes available from other plant species and reconstituted the synthesis of monoglycosylated saponins in yeast. Additionally, we established a culturing strategy in which applying methylated β-cyclodextrin to the culture medium allows the sequestration of heterologous nonvolatile hydrophobic terpenes, such as triterpene sapogenins, from engineered yeast cells into the growth medium, thereby greatly enhancing productivity. Together, our findings provide a sound base for the development of a synthetic biology platform for the production of bioactive triterpene sapo(ge)nins. PMID:24434554

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

KAUST Repository

Braguy, Justine

2016-05-26

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

Peptide mimic for influenza vaccination using nonnatural combinatorial chemistry

Science.gov (United States)

Miles, John J.; Tan, Mai Ping; Dolton, Garry; Galloway, Sarah A.E.; Laugel, Bruno; Makinde, Julia; Matthews, Katherine K.; Watkins, Thomas S.; Wong, Yide; Clark, Richard J.; Pentier, Johanne M.; Attaf, Meriem; Lissina, Anya; Ager, Ann; Gallimore, Awen; Gras, Stephanie; Rossjohn, Jamie; Burrows, Scott R.; Cole, David K.; Price, David A.

2018-01-01

Polypeptide vaccines effectively activate human T cells but suffer from poor biological stability, which confines both transport logistics and in vivo therapeutic activity. Synthetic biology has the potential to address these limitations through the generation of highly stable antigenic “mimics” using subunits that do not exist in the natural world. We developed a platform based on D–amino acid combinatorial chemistry and used this platform to reverse engineer a fully artificial CD8+ T cell agonist that mirrored the immunogenicity profile of a native epitope blueprint from influenza virus. This nonnatural peptide was highly stable in human serum and gastric acid, reflecting an intrinsic resistance to physical and enzymatic degradation. In vitro, the synthetic agonist stimulated and expanded an archetypal repertoire of polyfunctional human influenza virus–specific CD8+ T cells. In vivo, specific responses were elicited in naive humanized mice by subcutaneous vaccination, conferring protection from subsequent lethal influenza challenge. Moreover, the synthetic agonist was immunogenic after oral administration. This proof-of-concept study highlights the power of synthetic biology to expand the horizons of vaccine design and therapeutic delivery. PMID:29528337

ACRE: Absolute concentration robustness exploration in module-based combinatorial networks

KAUST Repository

Kuwahara, Hiroyuki; Umarov, Ramzan; Almasri, Islam; Gao, Xin

2017-01-01

To engineer cells for industrial-scale application, a deep understanding of how to design molecular control mechanisms to tightly maintain functional stability under various fluctuations is crucial. Absolute concentration robustness (ACR) is a category of robustness in reaction network models in which the steady-state concentration of a molecular species is guaranteed to be invariant even with perturbations in the other molecular species in the network. Here, we introduce a software tool, absolute concentration robustness explorer (ACRE), which efficiently explores combinatorial biochemical networks for the ACR property. ACRE has a user-friendly interface, and it can facilitate efficient analysis of key structural features that guarantee the presence and the absence of the ACR property from combinatorial networks. Such analysis is expected to be useful in synthetic biology as it can increase our understanding of how to design molecular mechanisms to tightly control the concentration of molecular species. ACRE is freely available at https://github.com/ramzan1990/ACRE.

ACRE: Absolute concentration robustness exploration in module-based combinatorial networks

KAUST Repository

Kuwahara, Hiroyuki

2017-03-01

To engineer cells for industrial-scale application, a deep understanding of how to design molecular control mechanisms to tightly maintain functional stability under various fluctuations is crucial. Absolute concentration robustness (ACR) is a category of robustness in reaction network models in which the steady-state concentration of a molecular species is guaranteed to be invariant even with perturbations in the other molecular species in the network. Here, we introduce a software tool, absolute concentration robustness explorer (ACRE), which efficiently explores combinatorial biochemical networks for the ACR property. ACRE has a user-friendly interface, and it can facilitate efficient analysis of key structural features that guarantee the presence and the absence of the ACR property from combinatorial networks. Such analysis is expected to be useful in synthetic biology as it can increase our understanding of how to design molecular mechanisms to tightly control the concentration of molecular species. ACRE is freely available at https://github.com/ramzan1990/ACRE.

Combinatorial commutative algebra

CERN Document Server

Miller, Ezra

2005-01-01

Offers an introduction to combinatorial commutative algebra, focusing on combinatorial techniques for multigraded polynomial rings, semigroup algebras, and determined rings. The chapters in this work cover topics ranging from homological invariants of monomial ideals and their polyhedral resolutions, to tools for studying algebraic varieties.

Dynamic combinatorial chemistry

NARCIS (Netherlands)

Otto, Sijbren; Furlan, Ricardo L.E.; Sanders, Jeremy K.M.

2002-01-01

A combinatorial library that responds to its target by increasing the concentration of strong binders at the expense of weak binders sounds ideal. Dynamic combinatorial chemistry has the potential to achieve exactly this. In this review, we will highlight the unique features that distinguish dynamic

Synthesis of new water-soluble metal-binding polymers: Combinatorial chemistry approach. 1998 annual progress report

International Nuclear Information System (INIS)

Kurth, M.J.; Miller, R.B.; Sawan, S.; Smith, B.F.

1998-01-01

'(1) Develop rapid discovery and optimization approaches to new water-soluble chelating polymers for use in Polymer Filtration (PF) systems, and (2) evaluate the concept of using water and organic soluble polymers as new solid supports for combinatorial synthesis. Polymer Filtration (PF), which uses water-soluble metal-binding polymers to sequester metal ions in dilute solution with ultrafiltration (UF) to separate the polymers, is a new technology to selectively remove or recover hazardous and valuable metal ions. Future directions in PF must include rapid development, testing, and characterization of new metal-binding polymers. Thus, the authors are building upon and adapting the combinatorial chemistry approach developed for rapid molecule generation for the drug industry to the rapid development of new chelating polymers. The authors have focused on four areas including the development of: (1) synthetic procedures, (2) small ultrafiltration equipment compatible with organic- and aqueous-based combinatorial synthesis, (3) rapid assay techniques, and (4) polymer characterization techniques.'

Tailored Polymer-Supported Templates in Dynamic Combinatorial Libraries : Simultaneous Selection, Amplification and Isolation of Synthetic Receptors

NARCIS (Netherlands)

Besenius, Pol; Cormack, Peter A.G.; Liu, Jingyuan; Otto, Sijbren; Sanders, Jeremy K.M.; Sherrington, David C.

2008-01-01

The thermodynamically controlled synthesis and isolation of macrocyclic receptors from dynamic combinatorial libraries has been achieved in a single step using a polymer-supported template. The templates were cinchona alkaloids which show interesting enantio- and diastereoselective molecular

Chromatin regulation at the frontier of synthetic biology

Science.gov (United States)

Keung, Albert J.; Joung, J. Keith; Khalil, Ahmad S.; Collins, James J.

2016-01-01

As synthetic biology approaches are extended to diverse applications throughout medicine, biotechnology and basic biological research, there is an increasing need to engineer yeast, plant and mammalian cells. Eukaryotic genomes are regulated by the diverse biochemical and biophysical states of chromatin, which brings distinct challenges, as well as opportunities, over applications in bacteria. Recent synthetic approaches, including `epigenome editing', have allowed the direct and functional dissection of many aspects of physiological chromatin regulation. These studies lay the foundation for biomedical and biotechnological engineering applications that could take advantage of the unique combinatorial and spatiotemporal layers of chromatin regulation to create synthetic systems of unprecedented sophistication. PMID:25668787

Relativity in Combinatorial Gravitational Fields

Directory of Open Access Journals (Sweden)

Mao Linfan

2010-04-01

Full Text Available A combinatorial spacetime $(mathscr{C}_G| uboverline{t}$ is a smoothly combinatorial manifold $mathscr{C}$ underlying a graph $G$ evolving on a time vector $overline{t}$. As we known, Einstein's general relativity is suitable for use only in one spacetime. What is its disguise in a combinatorial spacetime? Applying combinatorial Riemannian geometry enables us to present a combinatorial spacetime model for the Universe and suggest a generalized Einstein gravitational equation in such model. Forfinding its solutions, a generalized relativity principle, called projective principle is proposed, i.e., a physics law ina combinatorial spacetime is invariant under a projection on its a subspace and then a spherically symmetric multi-solutions ofgeneralized Einstein gravitational equations in vacuum or charged body are found. We also consider the geometrical structure in such solutions with physical formations, and conclude that an ultimate theory for the Universe maybe established if all such spacetimes in ${f R}^3$. Otherwise, our theory is only an approximate theory and endless forever.

Combinatorial Nano-Bio Interfaces.

Science.gov (United States)

Cai, Pingqiang; Zhang, Xiaoqian; Wang, Ming; Wu, Yun-Long; Chen, Xiaodong

2018-06-08

Nano-bio interfaces are emerging from the convergence of engineered nanomaterials and biological entities. Despite rapid growth, clinical translation of biomedical nanomaterials is heavily compromised by the lack of comprehensive understanding of biophysicochemical interactions at nano-bio interfaces. In the past decade, a few investigations have adopted a combinatorial approach toward decoding nano-bio interfaces. Combinatorial nano-bio interfaces comprise the design of nanocombinatorial libraries and high-throughput bioevaluation. In this Perspective, we address challenges in combinatorial nano-bio interfaces and call for multiparametric nanocombinatorics (composition, morphology, mechanics, surface chemistry), multiscale bioevaluation (biomolecules, organelles, cells, tissues/organs), and the recruitment of computational modeling and artificial intelligence. Leveraging combinatorial nano-bio interfaces will shed light on precision nanomedicine and its potential applications.

Synthetic Strategies and Applications of GaN Nanowires

Directory of Open Access Journals (Sweden)

Guoquan Suo

2014-01-01

Full Text Available GaN is an important III-V semiconductor material with a direct band gap of 3.4 eV at 300 K. The wide direct band gap makes GaN an attractive material for various applications. GaN nanowires have demonstrated significant potential as fundamental building blocks for nanoelectronic and nanophotonic devices and also offer substantial promise for integrated nanosystems. In this paper, we provide a comprehensive review on the general synthetic strategies, characterizations, and applications of GaN nanowires. We first summarize several growth techniques of GaN nanowires. Subsequently, we discuss mechanisms involved to generate GaN nanowires from different synthetic schemes and conditions. Then we review some characterization methods of GaN nanowires. Finally, several kinds of main applications of GaN nanowires are discussed.

Integer and combinatorial optimization

CERN Document Server

Nemhauser, George L

1999-01-01

Rave reviews for INTEGER AND COMBINATORIAL OPTIMIZATION ""This book provides an excellent introduction and survey of traditional fields of combinatorial optimization . . . It is indeed one of the best and most complete texts on combinatorial optimization . . . available. [And] with more than 700 entries, [it] has quite an exhaustive reference list.""-Optima ""A unifying approach to optimization problems is to formulate them like linear programming problems, while restricting some or all of the variables to the integers. This book is an encyclopedic resource for such f

On an extension of a combinatorial identity

Indian Academy of Sciences (India)

to an infinite family of 4-way combinatorial identities. In some particular cases we get even 5-way combinatorial identities which give us four new combinatorial versions of. Göllnitz–Gordon identities. Keywords. n-Color partitions; lattice paths; Frobenius partitions; Göllnitz–Gordon identities; combinatorial interpretations. 1.

Strategy revealing phenotypic differences among synthetic oscillator designs.

Science.gov (United States)

Lomnitz, Jason G; Savageau, Michael A

2014-09-19

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

Nonparametric combinatorial sequence models.

Science.gov (United States)

Wauthier, Fabian L; Jordan, Michael I; Jojic, Nebojsa

2011-11-01

This work considers biological sequences that exhibit combinatorial structures in their composition: groups of positions of the aligned sequences are "linked" and covary as one unit across sequences. If multiple such groups exist, complex interactions can emerge between them. Sequences of this kind arise frequently in biology but methodologies for analyzing them are still being developed. This article presents a nonparametric prior on sequences which allows combinatorial structures to emerge and which induces a posterior distribution over factorized sequence representations. We carry out experiments on three biological sequence families which indicate that combinatorial structures are indeed present and that combinatorial sequence models can more succinctly describe them than simpler mixture models. We conclude with an application to MHC binding prediction which highlights the utility of the posterior distribution over sequence representations induced by the prior. By integrating out the posterior, our method compares favorably to leading binding predictors.

Lanthanide-Based Metal Organic Frameworks: Synthetic Strategies and Catalytic Applications

NARCIS (Netherlands)

Pagis, C.; Ferbinteanu, M.; Rothenberg, G.; Grecea, S.

2016-01-01

This short critical review outlines the main synthetic strategies used in the designed synthesis of lanthanide-based metal organic frameworks (Ln-MOFs). It explains the impact of the choice of organic linker on the final network topology, and it highlights the applications of Ln-MOFs in the

MiYA, an efficient machine-learning workflow in conjunction with the YeastFab assembly strategy for combinatorial optimization of heterologous metabolic pathways in Saccharomyces cerevisiae.

Science.gov (United States)

Zhou, Yikang; Li, Gang; Dong, Junkai; Xing, Xin-Hui; Dai, Junbiao; Zhang, Chong

2018-05-01

Facing boosting ability to construct combinatorial metabolic pathways, how to search the metabolic sweet spot has become the rate-limiting step. We here reported an efficient Machine-learning workflow in conjunction with YeastFab Assembly strategy (MiYA) for combinatorial optimizing the large biosynthetic genotypic space of heterologous metabolic pathways in Saccharomyces cerevisiae. Using β-carotene biosynthetic pathway as example, we first demonstrated that MiYA has the power to search only a small fraction (2-5%) of combinatorial space to precisely tune the expression level of each gene with a machine-learning algorithm of an artificial neural network (ANN) ensemble to avoid over-fitting problem when dealing with a small number of training samples. We then applied MiYA to improve the biosynthesis of violacein. Feed with initial data from a colorimetric plate-based, pre-screened pool of 24 strains producing violacein, MiYA successfully predicted, and verified experimentally, the existence of a strain that showed a 2.42-fold titer improvement in violacein production among 3125 possible designs. Furthermore, MiYA was able to largely avoid the branch pathway of violacein biosynthesis that makes deoxyviolacein, and produces very pure violacein. Together, MiYA combines the advantages of standardized building blocks and machine learning to accelerate the Design-Build-Test-Learn (DBTL) cycle for combinatorial optimization of metabolic pathways, which could significantly accelerate the development of microbial cell factories. Copyright © 2018 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

A combinatorial approach to synthetic transcription factor-promoter combinations for yeast strain engineering

DEFF Research Database (Denmark)

Dossani, Zain Y.; Apel, Amanda Reider; Szmidt-Middleton, Heather

2018-01-01

regions, we have built a library of hybrid promoters that are regulated by a synthetic transcription factor. The hybrid promoters consist of native S. cerevisiae promoters, in which the operator regions have been replaced with sequences that are recognized by the bacterial LexA DNA binding protein....... Correspondingly, the synthetic transcription factor (TF) consists of the DNA binding domain of the LexA protein, fused with the human estrogen binding domain and the viral activator domain, VP16. The resulting system with a bacterial DNA binding domain avoids the transcription of native S. cerevisiae genes...... levels, using the same synthetic TF and a given estradiol. This set of promoters, in combination with our synthetic TF, has the potential to regulate numerous genes or pathways simultaneously, to multiple desired levels, in a single strain....

EcoFlex: A Multifunctional MoClo Kit for E. coli Synthetic Biology.

Science.gov (United States)

Moore, Simon J; Lai, Hung-En; Kelwick, Richard J R; Chee, Soo Mei; Bell, David J; Polizzi, Karen Marie; Freemont, Paul S

2016-10-21

Golden Gate cloning is a prominent DNA assembly tool in synthetic biology for the assembly of plasmid constructs often used in combinatorial pathway optimization, with a number of assembly kits developed specifically for yeast and plant-based expression. However, its use for synthetic biology in commonly used bacterial systems such as Escherichia coli has surprisingly been overlooked. Here, we introduce EcoFlex a simplified modular package of DNA parts for a variety of applications in E. coli, cell-free protein synthesis, protein purification and hierarchical assembly of transcription units based on the MoClo assembly standard. The kit features a library of constitutive promoters, T7 expression, RBS strength variants, synthetic terminators, protein purification tags and fluorescence proteins. We validate EcoFlex by assembling a 68-part containing (20 genes) plasmid (31 kb), characterize in vivo and in vitro library parts, and perform combinatorial pathway assembly, using pooled libraries of either fluorescent proteins or the biosynthetic genes for the antimicrobial pigment violacein as a proof-of-concept. To minimize pathway screening, we also introduce a secondary module design site to simplify MoClo pathway optimization. In summary, EcoFlex provides a standardized and multifunctional kit for a variety of applications in E. coli synthetic biology.

Combinatorial metabolic engineering of Pseudomonas putida KT2440 for efficient mineralization of 1,2,3-trichloropropane.

Science.gov (United States)

Gong, Ting; Xu, Xiaoqing; Che, You; Liu, Ruihua; Gao, Weixia; Zhao, Fengjie; Yu, Huilei; Liang, Jingnan; Xu, Ping; Song, Cunjiang; Yang, Chao

2017-08-01

An industrial waste, 1,2,3-trichloropropane (TCP), is toxic and extremely recalcitrant to biodegradation. To date, no natural TCP degraders able to mineralize TCP aerobically have been isolated. In this work, we engineered a biosafety Pseudomonas putida strain KT2440 for aerobic mineralization of TCP by implantation of a synthetic biodegradation pathway into the chromosome and further improved TCP mineralization using combinatorial engineering strategies. Initially, a synthetic pathway composed of haloalkane dehalogenase, haloalcohol dehalogenase and epoxide hydrolase was functionally assembled for the conversion of TCP into glycerol in P. putida KT2440. Then, the growth lag-phase of using glycerol as a growth precursor was eliminated by deleting the glpR gene, significantly enhancing the flux of carbon through the pathway. Subsequently, we improved the oxygen sequestering capacity of this strain through the heterologous expression of Vitreoscilla hemoglobin, which makes this strain able to mineralize TCP under oxygen-limited conditions. Lastly, we further improved intracellular energy charge (ATP/ADP ratio) and reducing power (NADPH/NADP + ratio) by deleting flagella-related genes in the genome of P. putida KT2440. The resulting strain (named KTU-TGVF) could efficiently utilize TCP as the sole source of carbon for growth. Degradation studies in a bioreactor highlight the value of this engineered strain for TCP bioremediation.

Quantum resonance for simulating combinatorial problems

International Nuclear Information System (INIS)

Zak, Michail; Fijany, Amir

2005-01-01

Quantum computing by simulations is based upon similarity between mathematical formalism of a quantum phenomenon and phenomena to be analyzed. In this Letter, the mathematical formalism of quantum resonance combined with tensor product decomposability of unitary evolutions is mapped onto a class of NP-complete combinatorial problems. It has been demonstrated that nature has polynomial resources for solving NP-complete problems and that will help to develop a new strategy for artificial intelligence, as well as to re-evaluate the role of natural selection in biological evolution

Combinatorial Hybrid Systems

DEFF Research Database (Denmark)

Larsen, Jesper Abildgaard; Wisniewski, Rafal; Grunnet, Jacob Deleuran

2008-01-01

indicates for a given face the future simplex. In the suggested definition we allow nondeterminacy in form of splitting and merging of solution trajectories. The combinatorial vector field gives rise to combinatorial counterparts of most concepts from dynamical systems, such as duals to vector fields, flow......, flow lines, fixed points and Lyapunov functions. Finally it will be shown how this theory extends to switched dynamical systems and an algorithmic overview of how to do supervisory control will be shown towards the end....

Synthetic Strategies in the Preparation of Polymer/Inorganic Hybrid Nanoparticles

Science.gov (United States)

Hood, Matthew A.; Mari, Margherita; Muñoz-Espí, Rafael

2014-01-01

This article reviews the recent advances and challenges in the preparation of polymer/inorganic hybrid nanoparticles. We mainly focus on synthetic strategies, basing our classification on whether the inorganic and the polymer components have been formed in situ or ex situ, of the hybrid material. Accordingly, four types of strategies are identified and described, referring to recent examples: (i) ex situ formation of the components and subsequent attachment or integration, either by covalent or noncovalent bonding; (ii) in situ polymerization in the presence of ex situ formed inorganic nanoparticles; (iii) in situ precipitation of the inorganic components on or in polymer structures; and (iv) strategies in which both polymer and inorganic component are simultaneously formed in situ. PMID:28788665

Application of combinatorial biocatalysis for a unique ring expansion of dihydroxymethylzearalenone.

Science.gov (United States)

Rich, Joseph O; Budde, Cheryl L; McConeghey, Luke D; Cotterill, Ian C; Mozhaev, Vadim V; Singh, Sheo B; Goetz, Michael A; Zhao, Annie; Michels, Peter C; Khmelnitsky, Yuri L

2009-06-01

Combinatorial biocatalysis was applied to generate a diverse set of dihydroxymethylzearalenone analogs with modified ring structure. In one representative chemoenzymatic reaction sequence, dihydroxymethylzearalenone was first subjected to a unique enzyme-catalyzed oxidative ring opening reaction that creates two new carboxylic groups on the molecule. These groups served as reaction sites for further derivatization involving biocatalytic ring closure reactions with structurally diverse bifunctional reagents, including different diols and diamines. As a result, a library of cyclic bislactones and bislactams was created, with modified ring structures covering chemical space and structure activity relationships unattainable by conventional synthetic means.

Peptide/protein-polymer conjugates: synthetic strategies and design concepts.

Science.gov (United States)

Gauthier, Marc A; Klok, Harm-Anton

2008-06-21

This feature article provides a compilation of tools available for preparing well-defined peptide/protein-polymer conjugates, which are defined as hybrid constructs combining (i) a defined number of peptide/protein segments with uniform chain lengths and defined monomer sequences (primary structure) with (ii) a defined number of synthetic polymer chains. The first section describes methods for post-translational, or direct, introduction of chemoselective handles onto natural or synthetic peptides/proteins. Addressed topics include the residue- and/or site-specific modification of peptides/proteins at Arg, Asp, Cys, Gln, Glu, Gly, His, Lys, Met, Phe, Ser, Thr, Trp, Tyr and Val residues and methods for producing peptides/proteins containing non-canonical amino acids by peptide synthesis and protein engineering. In the second section, methods for introducing chemoselective groups onto the side-chain or chain-end of synthetic polymers produced by radical, anionic, cationic, metathesis and ring-opening polymerization are described. The final section discusses convergent and divergent strategies for covalently assembling polymers and peptides/proteins. An overview of the use of chemoselective reactions such as Heck, Sonogashira and Suzuki coupling, Diels-Alder cycloaddition, Click chemistry, Staudinger ligation, Michael's addition, reductive alkylation and oxime/hydrazone chemistry for the convergent synthesis of peptide/protein-polymer conjugates is given. Divergent approaches for preparing peptide/protein-polymer conjugates which are discussed include peptide synthesis from synthetic polymer supports, polymerization from peptide/protein macroinitiators or chain transfer agents and the polymerization of peptide side-chain monomers.

cDREM: inferring dynamic combinatorial gene regulation.

Science.gov (United States)

Wise, Aaron; Bar-Joseph, Ziv

2015-04-01

Genes are often combinatorially regulated by multiple transcription factors (TFs). Such combinatorial regulation plays an important role in development and facilitates the ability of cells to respond to different stresses. While a number of approaches have utilized sequence and ChIP-based datasets to study combinational regulation, these have often ignored the combinational logic and the dynamics associated with such regulation. Here we present cDREM, a new method for reconstructing dynamic models of combinatorial regulation. cDREM integrates time series gene expression data with (static) protein interaction data. The method is based on a hidden Markov model and utilizes the sparse group Lasso to identify small subsets of combinatorially active TFs, their time of activation, and the logical function they implement. We tested cDREM on yeast and human data sets. Using yeast we show that the predicted combinatorial sets agree with other high throughput genomic datasets and improve upon prior methods developed to infer combinatorial regulation. Applying cDREM to study human response to flu, we were able to identify several combinatorial TF sets, some of which were known to regulate immune response while others represent novel combinations of important TFs.

Combinatorial designs constructions and analysis

CERN Document Server

Stinson, Douglas R

2004-01-01

Created to teach students many of the most important techniques used for constructing combinatorial designs, this is an ideal textbook for advanced undergraduate and graduate courses in combinatorial design theory. The text features clear explanations of basic designs, such as Steiner and Kirkman triple systems, mutual orthogonal Latin squares, finite projective and affine planes, and Steiner quadruple systems. In these settings, the student will master various construction techniques, both classic and modern, and will be well-prepared to construct a vast array of combinatorial designs. Design theory offers a progressive approach to the subject, with carefully ordered results. It begins with simple constructions that gradually increase in complexity. Each design has a construction that contains new ideas or that reinforces and builds upon similar ideas previously introduced. A new text/reference covering all apsects of modern combinatorial design theory. Graduates and professionals in computer science, applie...

Recursive deconvolution of combinatorial chemical libraries.

OpenAIRE

Erb, E; Janda, K D; Brenner, S

1994-01-01

A recursive strategy that solves for the active members of a chemical library is presented. A pentapeptide library with an alphabet of Gly, Leu, Phe, and Tyr (1024 members) was constructed on a solid support by the method of split synthesis. One member of this library (NH2-Tyr-Gly-Gly-Phe-Leu) is a native binder to a beta-endorphin antibody. A variation of the split synthesis approach is used to build the combinatorial library. In four vials, a member of the library's alphabet is coupled to a...

Combinatorial delivery of small interfering RNAs reduces RNAi efficacy by selective incorporation into RISC

Science.gov (United States)

Castanotto, Daniela; Sakurai, Kumi; Lingeman, Robert; Li, Haitang; Shively, Louise; Aagaard, Lars; Soifer, Harris; Gatignol, Anne; Riggs, Arthur; Rossi, John J.

2007-01-01

Despite the great potential of RNAi, ectopic expression of shRNA or siRNAs holds the inherent risk of competition for critical RNAi components, thus altering the regulatory functions of some cellular microRNAs. In addition, specific siRNA sequences can potentially hinder incorporation of other siRNAs when used in a combinatorial approach. We show that both synthetic siRNAs and expressed shRNAs compete against each other and with the endogenous microRNAs for transport and for incorporation into the RNA induced silencing complex (RISC). The same siRNA sequences do not display competition when expressed from a microRNA backbone. We also show that TAR RNA binding protein (TRBP) is one of the sensors for selection and incorporation of the guide sequence of interfering RNAs. These findings reveal that combinatorial siRNA approaches can be problematic and have important implications for the methodology of expression and use of therapeutic interfering RNAs. PMID:17660190

Combinatorial structures to modeling simple games and applications

Science.gov (United States)

Molinero, Xavier

2017-09-01

We connect three different topics: combinatorial structures, game theory and chemistry. In particular, we establish the bases to represent some simple games, defined as influence games, and molecules, defined from atoms, by using combinatorial structures. First, we characterize simple games as influence games using influence graphs. It let us to modeling simple games as combinatorial structures (from the viewpoint of structures or graphs). Second, we formally define molecules as combinations of atoms. It let us to modeling molecules as combinatorial structures (from the viewpoint of combinations). It is open to generate such combinatorial structures using some specific techniques as genetic algorithms, (meta-)heuristics algorithms and parallel programming, among others.

Dynamic combinatorial libraries : new opportunities in systems chemistry

NARCIS (Netherlands)

Hunt, Rosemary A. R.; Otto, Sijbren; Hunt, Rosemary A.R.

2011-01-01

Combinatorial chemistry is a tool for selecting molecules with special properties. Dynamic combinatorial chemistry started off aiming to be just that. However, unlike ordinary combinatorial chemistry, the interconnectedness of dynamic libraries gives them an extra dimension. An understanding of

Synthetic strategies for efficient conjugation of organometallic complexes with pendant protein reactive markers

KAUST Repository

Jantke, Dominik; Marziale, Alexander N.; Reiner, Thomas; Kraus, Florian; Herdtweck, Eberhardt; Raba, Andreas; Eppinger, Jö rg

2013-01-01

Site-directed conjugation of metal centers to proteins is fundamental for biological and bioinorganic applications of transition metals. However, methods for the site-selective introduction of metal centers remain scarce. Herein, we present broadly applicable synthetic strategies for the conjugation of bioactive molecules with a range of organometallic complexes. Following three different synthetic strategies, we were able to synthesize a small library of metal conjugated protein markers featuring different types of protein reactive sites (epoxides, phenylphosphonates, fluorosulfonates and fluorophosphonate groups) as well as different late transition metals (iron, ruthenium, rhodium, palladium and platinum). The products were isolated in moderate to excellent yields and high purity. Furthermore, X-ray diffraction of the metalated protein markers corroborates structural integrity of the metal complex and the protein reactive site. © 2013 Elsevier B.V. All rights reserved.

Synthetic strategies for efficient conjugation of organometallic complexes with pendant protein reactive markers

KAUST Repository

Jantke, Dominik

2013-11-01

Site-directed conjugation of metal centers to proteins is fundamental for biological and bioinorganic applications of transition metals. However, methods for the site-selective introduction of metal centers remain scarce. Herein, we present broadly applicable synthetic strategies for the conjugation of bioactive molecules with a range of organometallic complexes. Following three different synthetic strategies, we were able to synthesize a small library of metal conjugated protein markers featuring different types of protein reactive sites (epoxides, phenylphosphonates, fluorosulfonates and fluorophosphonate groups) as well as different late transition metals (iron, ruthenium, rhodium, palladium and platinum). The products were isolated in moderate to excellent yields and high purity. Furthermore, X-ray diffraction of the metalated protein markers corroborates structural integrity of the metal complex and the protein reactive site. © 2013 Elsevier B.V. All rights reserved.

Effects of Suboptimal Bidding in Combinatorial Auctions

Science.gov (United States)

Schneider, Stefan; Shabalin, Pasha; Bichler, Martin

Though the VCG auction assumes a central place in the mechanism design literature, there are a number of reasons for favoring iterative combinatorial auction designs. Several promising ascending auction formats have been developed throughout the past few years based on primal-dual and subgradient algorithms and linear programming theory. Prices are interpreted as a feasible dual solution and the provisional allocation is interpreted as a feasible primal solution. iBundle( 3) (Parkes and Ungar 2000), dVSV (de Vries et al. 2007) and the Ascending Proxy auction (Ausubel and Milgrom 2002) result in VCG payoffs when the coalitional value function satisfies the buyer submodularity condition and bidders bid straightforward, which is an expost Nash equilibrium in that case. iBEA and CreditDebit auctions (Mishra and Parkes 2007) do not even require the buyer submodularity condition and achieve the same properties for general valuations. In many situations, however, one cannot assume bidders to bid straightforward and it is not clear from the theory how these non-linear personalized price auctions (NLPPAs) perform in this case. Robustness of auctions with respect to different bidding behavior is therefore a critical issue for any application. We have conducted a large number of computational experiments to analyze the performance of NLPPA designs with respect to different bidding strategies and different valuation models. We compare the results of NLPPAs to those of the VCG auction and those of iterative combinatorial auctions with approximate linear prices, such as ALPS (Bichler et al. 2009) and the Combinatorial Clock auction (Porter et al. 2003).

Boltzmann Oracle for Combinatorial Systems

OpenAIRE

Pivoteau , Carine; Salvy , Bruno; Soria , Michèle

2008-01-01

International audience; Boltzmann random generation applies to well-defined systems of recursive combinatorial equations. It relies on oracles giving values of the enumeration generating series inside their disk of convergence. We show that the combinatorial systems translate into numerical iteration schemes that provide such oracles. In particular, we give a fast oracle based on Newton iteration.

Characterizing the combinatorial beam angle selection problem

Science.gov (United States)

Bangert, Mark; Ziegenhein, Peter; Oelfke, Uwe

2012-10-01

The beam angle selection (BAS) problem in intensity-modulated radiation therapy is often interpreted as a combinatorial optimization problem, i.e. finding the best combination of η beams in a discrete set of candidate beams. It is well established that the combinatorial BAS problem may be solved efficiently with metaheuristics such as simulated annealing or genetic algorithms. However, the underlying parameters of the optimization process, such as the inclusion of non-coplanar candidate beams, the angular resolution in the space of candidate beams, and the number of evaluated beam ensembles as well as the relative performance of different metaheuristics have not yet been systematically investigated. We study these open questions in a meta-analysis of four strategies for combinatorial optimization in order to provide a reference for future research related to the BAS problem in intensity-modulated radiation therapy treatment planning. We introduce a high-performance inverse planning engine for BAS. It performs a full fluence optimization for ≈3600 treatment plans per hour while handling up to 50 GB of dose influence data (≈1400 candidate beams). For three head and neck patients, we compare the relative performance of a genetic, a cross-entropy, a simulated annealing and a naive iterative algorithm. The selection of ensembles with 5, 7, 9 and 11 beams considering either only coplanar or all feasible candidate beams is studied for an angular resolution of 5°, 10°, 15° and 20° in the space of candidate beams. The impact of different convergence criteria is investigated in comparison to a fixed termination after the evaluation of 10 000 beam ensembles. In total, our simulations comprise a full fluence optimization for about 3000 000 treatment plans. All four combinatorial BAS strategies yield significant improvements of the objective function value and of the corresponding dose distributions compared to standard beam configurations with equi

Characterizing the combinatorial beam angle selection problem

International Nuclear Information System (INIS)

Bangert, Mark; Ziegenhein, Peter; Oelfke, Uwe

2012-01-01

The beam angle selection (BAS) problem in intensity-modulated radiation therapy is often interpreted as a combinatorial optimization problem, i.e. finding the best combination of η beams in a discrete set of candidate beams. It is well established that the combinatorial BAS problem may be solved efficiently with metaheuristics such as simulated annealing or genetic algorithms. However, the underlying parameters of the optimization process, such as the inclusion of non-coplanar candidate beams, the angular resolution in the space of candidate beams, and the number of evaluated beam ensembles as well as the relative performance of different metaheuristics have not yet been systematically investigated. We study these open questions in a meta-analysis of four strategies for combinatorial optimization in order to provide a reference for future research related to the BAS problem in intensity-modulated radiation therapy treatment planning. We introduce a high-performance inverse planning engine for BAS. It performs a full fluence optimization for ≈3600 treatment plans per hour while handling up to 50 GB of dose influence data (≈1400 candidate beams). For three head and neck patients, we compare the relative performance of a genetic, a cross-entropy, a simulated annealing and a naive iterative algorithm. The selection of ensembles with 5, 7, 9 and 11 beams considering either only coplanar or all feasible candidate beams is studied for an angular resolution of 5°, 10°, 15° and 20° in the space of candidate beams. The impact of different convergence criteria is investigated in comparison to a fixed termination after the evaluation of 10 000 beam ensembles. In total, our simulations comprise a full fluence optimization for about 3000 000 treatment plans. All four combinatorial BAS strategies yield significant improvements of the objective function value and of the corresponding dose distributions compared to standard beam configurations with equi

A Synthetic Biology Framework for Programming Eukaryotic Transcription Functions

Science.gov (United States)

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

2013-01-01

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

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

Science.gov (United States)

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

2014-01-01

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

Combinatorial Interpretation of General Eulerian Numbers

OpenAIRE

Tingyao Xiong; Jonathan I. Hall; Hung-Ping Tsao

2014-01-01

Since 1950s, mathematicians have successfully interpreted the traditional Eulerian numbers and $q-$Eulerian numbers combinatorially. In this paper, the authors give a combinatorial interpretation to the general Eulerian numbers defined on general arithmetic progressions { a, a+d, a+2d,...}.

High-flexibility combinatorial peptide synthesis with laser-based transfer of monomers in solid matrix material.

Science.gov (United States)

Loeffler, Felix F; Foertsch, Tobias C; Popov, Roman; Mattes, Daniela S; Schlageter, Martin; Sedlmayr, Martyna; Ridder, Barbara; Dang, Florian-Xuan; von Bojničić-Kninski, Clemens; Weber, Laura K; Fischer, Andrea; Greifenstein, Juliane; Bykovskaya, Valentina; Buliev, Ivan; Bischoff, F Ralf; Hahn, Lothar; Meier, Michael A R; Bräse, Stefan; Powell, Annie K; Balaban, Teodor Silviu; Breitling, Frank; Nesterov-Mueller, Alexander

2016-06-14

Laser writing is used to structure surfaces in many different ways in materials and life sciences. However, combinatorial patterning applications are still limited. Here we present a method for cost-efficient combinatorial synthesis of very-high-density peptide arrays with natural and synthetic monomers. A laser automatically transfers nanometre-thin solid material spots from different donor slides to an acceptor. Each donor bears a thin polymer film, embedding one type of monomer. Coupling occurs in a separate heating step, where the matrix becomes viscous and building blocks diffuse and couple to the acceptor surface. Furthermore, we can consecutively deposit two material layers of activation reagents and amino acids. Subsequent heat-induced mixing facilitates an in situ activation and coupling of the monomers. This allows us to incorporate building blocks with click chemistry compatibility or a large variety of commercially available non-activated, for example, posttranslationally modified building blocks into the array's peptides with >17,000 spots per cm(2).

Combinatorial optimization on a Boltzmann machine

NARCIS (Netherlands)

Korst, J.H.M.; Aarts, E.H.L.

1989-01-01

We discuss the problem of solving (approximately) combinatorial optimization problems on a Boltzmann machine. It is shown for a number of combinatorial optimization problems how they can be mapped directly onto a Boltzmann machine by choosing appropriate connection patterns and connection strengths.

Combinatorial synthesis of natural products

DEFF Research Database (Denmark)

Nielsen, John

2002-01-01

Combinatorial syntheses allow production of compound libraries in an expeditious and organized manner immediately applicable for high-throughput screening. Natural products possess a pedigree to justify quality and appreciation in drug discovery and development. Currently, we are seeing a rapid...... increase in application of natural products in combinatorial chemistry and vice versa. The therapeutic areas of infectious disease and oncology still dominate but many new areas are emerging. Several complex natural products have now been synthesised by solid-phase methods and have created the foundation...... for preparation of combinatorial libraries. In other examples, natural products or intermediates have served as building blocks or scaffolds in the synthesis of complex natural products, bioactive analogues or designed hybrid molecules. Finally, structural motifs from the biologically active parent molecule have...

Tumor-targeting peptides from combinatorial libraries*

Science.gov (United States)

Liu, Ruiwu; Li, Xiaocen; Xiao, Wenwu; Lam, Kit S.

2018-01-01

Cancer is one of the major and leading causes of death worldwide. Two of the greatest challenges infighting cancer are early detection and effective treatments with no or minimum side effects. Widespread use of targeted therapies and molecular imaging in clinics requires high affinity, tumor-specific agents as effective targeting vehicles to deliver therapeutics and imaging probes to the primary or metastatic tumor sites. Combinatorial libraries such as phage-display and one-bead one-compound (OBOC) peptide libraries are powerful approaches in discovering tumor-targeting peptides. This review gives an overview of different combinatorial library technologies that have been used for the discovery of tumor-targeting peptides. Examples of tumor-targeting peptides identified from each combinatorial library method will be discussed. Published tumor-targeting peptide ligands and their applications will also be summarized by the combinatorial library methods and their corresponding binding receptors. PMID:27210583

Neural Meta-Memes Framework for Combinatorial Optimization

Science.gov (United States)

Song, Li Qin; Lim, Meng Hiot; Ong, Yew Soon

In this paper, we present a Neural Meta-Memes Framework (NMMF) for combinatorial optimization. NMMF is a framework which models basic optimization algorithms as memes and manages them dynamically when solving combinatorial problems. NMMF encompasses neural networks which serve as the overall planner/coordinator to balance the workload between memes. We show the efficacy of the proposed NMMF through empirical study on a class of combinatorial problem, the quadratic assignment problem (QAP).

Number systems and combinatorial problems

OpenAIRE

Yordzhev, Krasimir

2014-01-01

The present work has been designed for students in secondary school and their teachers in mathematics. We will show how with the help of our knowledge of number systems we can solve problems from other fields of mathematics for example in combinatorial analysis and most of all when proving some combinatorial identities. To demonstrate discussed in this article method we have chosen several suitable mathematical tasks.

Introduction to combinatorial geometry

International Nuclear Information System (INIS)

Gabriel, T.A.; Emmett, M.B.

1985-01-01

The combinatorial geometry package as used in many three-dimensional multimedia Monte Carlo radiation transport codes, such as HETC, MORSE, and EGS, is becoming the preferred way to describe simple and complicated systems. Just about any system can be modeled using the package with relatively few input statements. This can be contrasted against the older style geometry packages in which the required input statements could be large even for relatively simple systems. However, with advancements come some difficulties. The users of combinatorial geometry must be able to visualize more, and, in some instances, all of the system at a time. Errors can be introduced into the modeling which, though slight, and at times hard to detect, can have devastating effects on the calculated results. As with all modeling packages, the best way to learn the combinatorial geometry is to use it, first on a simple system then on more complicated systems. The basic technique for the description of the geometry consists of defining the location and shape of the various zones in terms of the intersections and unions of geometric bodies. The geometric bodies which are generally included in most combinatorial geometry packages are: (1) box, (2) right parallelepiped, (3) sphere, (4) right circular cylinder, (5) right elliptic cylinder, (6) ellipsoid, (7) truncated right cone, (8) right angle wedge, and (9) arbitrary polyhedron. The data necessary to describe each of these bodies are given. As can be easily noted, there are some subsets included for simplicity

Development of combinatorial chemistry methods for coatings: high-throughput adhesion evaluation and scale-up of combinatorial leads.

Science.gov (United States)

Potyrailo, Radislav A; Chisholm, Bret J; Morris, William G; Cawse, James N; Flanagan, William P; Hassib, Lamyaa; Molaison, Chris A; Ezbiansky, Karin; Medford, George; Reitz, Hariklia

2003-01-01

Coupling of combinatorial chemistry methods with high-throughput (HT) performance testing and measurements of resulting properties has provided a powerful set of tools for the 10-fold accelerated discovery of new high-performance coating materials for automotive applications. Our approach replaces labor-intensive steps with automated systems for evaluation of adhesion of 8 x 6 arrays of coating elements that are discretely deposited on a single 9 x 12 cm plastic substrate. Performance of coatings is evaluated with respect to their resistance to adhesion loss, because this parameter is one of the primary considerations in end-use automotive applications. Our HT adhesion evaluation provides previously unavailable capabilities of high speed and reproducibility of testing by using a robotic automation, an expanded range of types of tested coatings by using the coating tagging strategy, and an improved quantitation by using high signal-to-noise automatic imaging. Upon testing, the coatings undergo changes that are impossible to quantitatively predict using existing knowledge. Using our HT methodology, we have developed several coatings leads. These HT screening results for the best coating compositions have been validated on the traditional scales of coating formulation and adhesion loss testing. These validation results have confirmed the superb performance of combinatorially developed coatings over conventional coatings on the traditional scale.

Engineered biomaterial and biophysical stimulation as combinatorial strategies to address prosthetic infection by pathogenic bacteria.

Science.gov (United States)

Boda, Sunil Kumar; Basu, Bikramjit

2017-10-01

A plethora of antimicrobial strategies are being developed to address prosthetic infection. The currently available methods for implant infection treatment include the use of antibiotics and revision surgery. Among the bacterial strains, Staphylococcus species pose significant challenges particularly, with regard to hospital acquired infections. In order to combat such life threatening infectious diseases, researchers have developed implantable biomaterials incorporating nanoparticles, antimicrobial reinforcements, surface coatings, slippery/non-adhesive and contact killing surfaces. This review discusses a few of the biomaterial and biophysical antimicrobial strategies, which are in the developmental stage and actively being pursued by several research groups. The clinical efficacy of biophysical stimulation methods such as ultrasound, electric and magnetic field treatments against prosthetic infection depends critically on the stimulation protocol and parameters of the treatment modality. A common thread among the three biophysical stimulation methods is the mechanism of bactericidal action, which is centered on biophysical rupture of bacterial membranes, the generation of reactive oxygen species (ROS) and bacterial membrane depolarization evoked by the interference of essential ion-transport. Although the extent of antimicrobial effect, normally achieved through biophysical stimulation protocol is insufficient to warrant therapeutic application, a combination of antibiotic/ROS inducing agents and biophysical stimulation methods can elicit a clinically relevant reduction in viable bacterial numbers. In this review, we present a detailed account of both the biomaterial and biophysical approaches for achieving maximum bacterial inactivation. Summarizing, the biophysical stimulation methods in a combinatorial manner with material based strategies can be a more potent solution to control bacterial infections. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B

Introduction to combinatorial designs

CERN Document Server

Wallis, WD

2007-01-01

Combinatorial theory is one of the fastest growing areas of modern mathematics. Focusing on a major part of this subject, Introduction to Combinatorial Designs, Second Edition provides a solid foundation in the classical areas of design theory as well as in more contemporary designs based on applications in a variety of fields. After an overview of basic concepts, the text introduces balanced designs and finite geometries. The author then delves into balanced incomplete block designs, covering difference methods, residual and derived designs, and resolvability. Following a chapter on the e

Use of combinatorial chemistry to speed drug discovery.

Science.gov (United States)

Rádl, S

1998-10-01

IBC's International Conference on Integrating Combinatorial Chemistry into the Discovery Pipeline was held September 14-15, 1998. The program started with a pre-conference workshop on High-Throughput Compound Characterization and Purification. The agenda of the main conference was divided into sessions of Synthesis, Automation and Unique Chemistries; Integrating Combinatorial Chemistry, Medicinal Chemistry and Screening; Combinatorial Chemistry Applications for Drug Discovery; and Information and Data Management. This meeting was an excellent opportunity to see how big pharma, biotech and service companies are addressing the current bottlenecks in combinatorial chemistry to speed drug discovery. (c) 1998 Prous Science. All rights reserved.

Crossover versus Mutation: A Comparative Analysis of the Evolutionary Strategy of Genetic Algorithms Applied to Combinatorial Optimization Problems

Directory of Open Access Journals (Sweden)

E. Osaba

2014-01-01

Full Text Available Since their first formulation, genetic algorithms (GAs have been one of the most widely used techniques to solve combinatorial optimization problems. The basic structure of the GAs is known by the scientific community, and thanks to their easy application and good performance, GAs are the focus of a lot of research works annually. Although throughout history there have been many studies analyzing various concepts of GAs, in the literature there are few studies that analyze objectively the influence of using blind crossover operators for combinatorial optimization problems. For this reason, in this paper a deep study on the influence of using them is conducted. The study is based on a comparison of nine techniques applied to four well-known combinatorial optimization problems. Six of the techniques are GAs with different configurations, and the remaining three are evolutionary algorithms that focus exclusively on the mutation process. Finally, to perform a reliable comparison of these results, a statistical study of them is made, performing the normal distribution z-test.

Crossover versus Mutation: A Comparative Analysis of the Evolutionary Strategy of Genetic Algorithms Applied to Combinatorial Optimization Problems

Science.gov (United States)

Osaba, E.; Carballedo, R.; Diaz, F.; Onieva, E.; de la Iglesia, I.; Perallos, A.

2014-01-01

Since their first formulation, genetic algorithms (GAs) have been one of the most widely used techniques to solve combinatorial optimization problems. The basic structure of the GAs is known by the scientific community, and thanks to their easy application and good performance, GAs are the focus of a lot of research works annually. Although throughout history there have been many studies analyzing various concepts of GAs, in the literature there are few studies that analyze objectively the influence of using blind crossover operators for combinatorial optimization problems. For this reason, in this paper a deep study on the influence of using them is conducted. The study is based on a comparison of nine techniques applied to four well-known combinatorial optimization problems. Six of the techniques are GAs with different configurations, and the remaining three are evolutionary algorithms that focus exclusively on the mutation process. Finally, to perform a reliable comparison of these results, a statistical study of them is made, performing the normal distribution z-test. PMID:25165731

Asessing for Structural Understanding in Childrens' Combinatorial Problem Solving.

Science.gov (United States)

English, Lyn

1999-01-01

Assesses children's structural understanding of combinatorial problems when presented in a variety of task situations. Provides an explanatory model of students' combinatorial understandings that informs teaching and assessment. Addresses several components of children's structural understanding of elementary combinatorial problems. (Contains 50…

Dynamic combinatorial chemistry with diselenides and disulfides in water

DEFF Research Database (Denmark)

Rasmussen, Brian; Sørensen, Anne; Gotfredsen, Henrik

2014-01-01

Diselenide exchange is introduced as a reversible reaction in dynamic combinatorial chemistry in water. At neutral pH, diselenides are found to mix with disulfides and form dynamic combinatorial libraries of diselenides, disulfides, and selenenylsulfides. This journal is......Diselenide exchange is introduced as a reversible reaction in dynamic combinatorial chemistry in water. At neutral pH, diselenides are found to mix with disulfides and form dynamic combinatorial libraries of diselenides, disulfides, and selenenylsulfides. This journal is...

Fourier analysis in combinatorial number theory

International Nuclear Information System (INIS)

Shkredov, Il'ya D

2010-01-01

In this survey applications of harmonic analysis to combinatorial number theory are considered. Discussion topics include classical problems of additive combinatorics, colouring problems, higher-order Fourier analysis, theorems about sets of large trigonometric sums, results on estimates for trigonometric sums over subgroups, and the connection between combinatorial and analytic number theory. Bibliography: 162 titles.

Fourier analysis in combinatorial number theory

Energy Technology Data Exchange (ETDEWEB)

Shkredov, Il' ya D [M. V. Lomonosov Moscow State University, Moscow (Russian Federation)

2010-09-16

In this survey applications of harmonic analysis to combinatorial number theory are considered. Discussion topics include classical problems of additive combinatorics, colouring problems, higher-order Fourier analysis, theorems about sets of large trigonometric sums, results on estimates for trigonometric sums over subgroups, and the connection between combinatorial and analytic number theory. Bibliography: 162 titles.

Solid-Phase Synthesis of Small Molecule Libraries using Double Combinatorial Chemistry

DEFF Research Database (Denmark)

Nielsen, John; Jensen, Flemming R.

1997-01-01

The first synthesis of a combinatorial library using double combinatorial chemistry is presented. Coupling of unprotected Fmoc-tyrosine to the solid support was followed by Mitsunobu O-alkylation. Introduction of a diacid linker yields a system in which the double combinatorial step can be demons......The first synthesis of a combinatorial library using double combinatorial chemistry is presented. Coupling of unprotected Fmoc-tyrosine to the solid support was followed by Mitsunobu O-alkylation. Introduction of a diacid linker yields a system in which the double combinatorial step can...

Local formulae for combinatorial Pontryagin classes

International Nuclear Information System (INIS)

Gaifullin, Alexander A

2004-01-01

Let p(|K|) be the characteristic class of a combinatorial manifold K given by a polynomial p in the rational Pontryagin classes of K. We prove that for any polynomial p there is a function taking each combinatorial manifold K to a cycle z p (K) in its rational simplicial chains such that: 1) the Poincare dual of z p (K) represents the cohomology class p(|K|); 2) the coefficient of each simplex Δ in the cycle z p (K) is determined solely by the combinatorial type of linkΔ. We explicitly describe all such functions for the first Pontryagin class. We obtain estimates for the denominators of the coefficients of the simplices in the cycles z p (K)

Heterogenous phase as a mean in combinatorial chemistry

International Nuclear Information System (INIS)

Abdel-Hamid, S.G.

2007-01-01

Combinatorial chemistry is a rapid and inexpensive technique for the synthesis of hundreds of thousands of organic compounds of potential medicinal activity. In the past few decades a large number of combinatorial libraries have been constructed, and significantly supplement the chemical diversity of the traditional collections of the potentially active medicinal compounds. Solid phase synthesis was used to enrich the combinatorial chemistry libraries, through the use of solid supports (resins) and their modified forms. Most of the new libraries of compounds appeared recently, were synthesized by the use of solid-phase. Solid-phase combinatorial chemistry (SPCC) is now considered as an outstanding branch in pharmaceutical chemistry research and used extensively as a tool for drug discovery within the context of high-throughput chemical synthesis. The best pure libraries synthesized by the use of solid phase combinatorial chemistry (SPCC) may well be those of intermediate complexity that are free of artifact-causing nuisance compounds. (author)

MIFT: GIFT Combinatorial Geometry Input to VCS Code

Science.gov (United States)

1977-03-01

r-w w-^ H ^ß0318is CQ BRL °RCUMr REPORT NO. 1967 —-S: ... MIFT: GIFT COMBINATORIAL GEOMETRY INPUT TO VCS CODE Albert E...TITLE (and Subtitle) MIFT: GIFT Combinatorial Geometry Input to VCS Code S. TYPE OF REPORT & PERIOD COVERED FINAL 6. PERFORMING ORG. REPORT NUMBER...Vehicle Code System (VCS) called MORSE was modified to accept the GIFT combinatorial geometry package. GIFT , as opposed to the geometry package

Combinatorial optimization theory and algorithms

CERN Document Server

Korte, Bernhard

2018-01-01

This comprehensive textbook on combinatorial optimization places special emphasis on theoretical results and algorithms with provably good performance, in contrast to heuristics. It is based on numerous courses on combinatorial optimization and specialized topics, mostly at graduate level. This book reviews the fundamentals, covers the classical topics (paths, flows, matching, matroids, NP-completeness, approximation algorithms) in detail, and proceeds to advanced and recent topics, some of which have not appeared in a textbook before. Throughout, it contains complete but concise proofs, and also provides numerous exercises and references. This sixth edition has again been updated, revised, and significantly extended. Among other additions, there are new sections on shallow-light trees, submodular function maximization, smoothed analysis of the knapsack problem, the (ln 4+ɛ)-approximation for Steiner trees, and the VPN theorem. Thus, this book continues to represent the state of the art of combinatorial opti...

Combinatorial stresses kill pathogenic Candida species

Science.gov (United States)

Kaloriti, Despoina; Tillmann, Anna; Cook, Emily; Jacobsen, Mette; You, Tao; Lenardon, Megan; Ames, Lauren; Barahona, Mauricio; Chandrasekaran, Komelapriya; Coghill, George; Goodman, Daniel; Gow, Neil A. R.; Grebogi, Celso; Ho, Hsueh-Lui; Ingram, Piers; McDonagh, Andrew; De Moura, Alessandro P. S.; Pang, Wei; Puttnam, Melanie; Radmaneshfar, Elahe; Romano, Maria Carmen; Silk, Daniel; Stark, Jaroslav; Stumpf, Michael; Thiel, Marco; Thorne, Thomas; Usher, Jane; Yin, Zhikang; Haynes, Ken; Brown, Alistair J. P.

2012-01-01

Pathogenic microbes exist in dynamic niches and have evolved robust adaptive responses to promote survival in their hosts. The major fungal pathogens of humans, Candida albicans and Candida glabrata, are exposed to a range of environmental stresses in their hosts including osmotic, oxidative and nitrosative stresses. Significant efforts have been devoted to the characterization of the adaptive responses to each of these stresses. In the wild, cells are frequently exposed simultaneously to combinations of these stresses and yet the effects of such combinatorial stresses have not been explored. We have developed a common experimental platform to facilitate the comparison of combinatorial stress responses in C. glabrata and C. albicans. This platform is based on the growth of cells in buffered rich medium at 30°C, and was used to define relatively low, medium and high doses of osmotic (NaCl), oxidative (H 2O2) and nitrosative stresses (e.g., dipropylenetriamine (DPTA)-NONOate). The effects of combinatorial stresses were compared with the corresponding individual stresses under these growth conditions. We show for the first time that certain combinations of combinatorial stress are especially potent in terms of their ability to kill C. albicans and C. glabrata and/or inhibit their growth. This was the case for combinations of osmotic plus oxidative stress and for oxidative plus nitrosative stress. We predict that combinatorial stresses may be highly signif cant in host defences against these pathogenic yeasts. PMID:22463109

Two is better than one; toward a rational design of combinatorial therapy.

Science.gov (United States)

Chen, Sheng-Hong; Lahav, Galit

2016-12-01

Drug combination is an appealing strategy for combating the heterogeneity of tumors and evolution of drug resistance. However, the rationale underlying combinatorial therapy is often not well established due to lack of understandings of the specific pathways responding to the drugs, and their temporal dynamics following each treatment. Here we present several emerging trends in harnessing properties of biological systems for the optimal design of drug combinations, including the type of drugs, specific concentration, sequence of addition and the temporal schedule of treatments. We highlight recent studies showing different approaches for efficient design of drug combinations including single-cell signaling dynamics, adaption and pathway crosstalk. Finally, we discuss novel and feasible approaches that can facilitate the optimal design of combinatorial therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Toward Chemical Implementation of Encoded Combinatorial Libraries

DEFF Research Database (Denmark)

Nielsen, John; Janda, Kim D.

1994-01-01

The recent application of "combinatorial libraries" to supplement existing drug screening processes might simplify and accelerate the search for new lead compounds or drugs. Recently, a scheme for encoded combinatorial chemistry was put forward to surmount a number of the limitations possessed...

A New Approach for Proving or Generating Combinatorial Identities

Science.gov (United States)

Gonzalez, Luis

2010-01-01

A new method for proving, in an immediate way, many combinatorial identities is presented. The method is based on a simple recursive combinatorial formula involving n + 1 arbitrary real parameters. Moreover, this formula enables one not only to prove, but also generate many different combinatorial identities (not being required to know them "a…

A dynamical systems model for combinatorial cancer therapy enhances oncolytic adenovirus efficacy by MEK-inhibition.

Science.gov (United States)

Bagheri, Neda; Shiina, Marisa; Lauffenburger, Douglas A; Korn, W Michael

2011-02-01

Oncolytic adenoviruses, such as ONYX-015, have been tested in clinical trials for currently untreatable tumors, but have yet to demonstrate adequate therapeutic efficacy. The extent to which viruses infect targeted cells determines the efficacy of this approach but many tumors down-regulate the Coxsackievirus and Adenovirus Receptor (CAR), rendering them less susceptible to infection. Disrupting MAPK pathway signaling by pharmacological inhibition of MEK up-regulates CAR expression, offering possible enhanced adenovirus infection. MEK inhibition, however, interferes with adenovirus replication due to resulting G1-phase cell cycle arrest. Therefore, enhanced efficacy will depend on treatment protocols that productively balance these competing effects. Predictive understanding of how to attain and enhance therapeutic efficacy of combinatorial treatment is difficult since the effects of MEK inhibitors, in conjunction with adenovirus/cell interactions, are complex nonlinear dynamic processes. We investigated combinatorial treatment strategies using a mathematical model that predicts the impact of MEK inhibition on tumor cell proliferation, ONYX-015 infection, and oncolysis. Specifically, we fit a nonlinear differential equation system to dedicated experimental data and analyzed the resulting simulations for favorable treatment strategies. Simulations predicted enhanced combinatorial therapy when both treatments were applied simultaneously; we successfully validated these predictions in an ensuing explicit test study. Further analysis revealed that a CAR-independent mechanism may be responsible for amplified virus production and cell death. We conclude that integrated computational and experimental analysis of combinatorial therapy provides a useful means to identify treatment/infection protocols that yield clinically significant oncolysis. Enhanced oncolytic therapy has the potential to dramatically improve non-surgical cancer treatment, especially in locally advanced

Combinatorial methods with computer applications

CERN Document Server

Gross, Jonathan L

2007-01-01

Combinatorial Methods with Computer Applications provides in-depth coverage of recurrences, generating functions, partitions, and permutations, along with some of the most interesting graph and network topics, design constructions, and finite geometries. Requiring only a foundation in discrete mathematics, it can serve as the textbook in a combinatorial methods course or in a combined graph theory and combinatorics course.After an introduction to combinatorics, the book explores six systematic approaches within a comprehensive framework: sequences, solving recurrences, evaluating summation exp

Electricity price forecast using Combinatorial Neural Network trained by a new stochastic search method

International Nuclear Information System (INIS)

Abedinia, O.; Amjady, N.; Shafie-khah, M.; Catalão, J.P.S.

2015-01-01

Highlights: • Presenting a Combinatorial Neural Network. • Suggesting a new stochastic search method. • Adapting the suggested method as a training mechanism. • Proposing a new forecast strategy. • Testing the proposed strategy on real-world electricity markets. - Abstract: Electricity price forecast is key information for successful operation of electricity market participants. However, the time series of electricity price has nonlinear, non-stationary and volatile behaviour and so its forecast method should have high learning capability to extract the complex input/output mapping function of electricity price. In this paper, a Combinatorial Neural Network (CNN) based forecasting engine is proposed to predict the future values of price data. The CNN-based forecasting engine is equipped with a new training mechanism for optimizing the weights of the CNN. This training mechanism is based on an efficient stochastic search method, which is a modified version of chemical reaction optimization algorithm, giving high learning ability to the CNN. The proposed price forecast strategy is tested on the real-world electricity markets of Pennsylvania–New Jersey–Maryland (PJM) and mainland Spain and its obtained results are extensively compared with the results obtained from several other forecast methods. These comparisons illustrate effectiveness of the proposed strategy.

The priming of basic combinatory responses in MEG.

Science.gov (United States)

Blanco-Elorrieta, Esti; Ferreira, Victor S; Del Prato, Paul; Pylkkänen, Liina

2018-01-01

Priming has been a powerful tool for the study of human memory and especially the memory representations relevant for language. However, although it is well established that lexical access can be primed, we do not know exactly what types of computations can be primed above the word level. This work took a neurobiological approach and assessed the ways in which the complex representation of a minimal combinatory phrase, such as red boat, can be primed, as evidenced by the spatiotemporal profiles of magnetoencephalography (MEG) signals. Specifically, we built upon recent progress on the neural signatures of phrasal composition and tested whether the brain activities implicated for the basic combination of two words could be primed. In two experiments, MEG was recorded during a picture naming task where the prime trials were designed to replicate previously reported combinatory effects and the target trials to test whether those combinatory effects could be primed. The manipulation of the primes was successful in eliciting larger activity for adjective-noun combinations than single nouns in left anterior temporal and ventromedial prefrontal cortices, replicating prior MEG studies on parallel contrasts. Priming of similarly timed activity was observed during target trials in anterior temporal cortex, but only when the prime and target shared an adjective. No priming in temporal cortex was observed for single word repetition and two control tasks showed that the priming effect was not elicited if the prime pictures were simply viewed but not named. In sum, this work provides evidence that very basic combinatory operations can be primed, with the necessity for some lexical overlap between prime and target suggesting combinatory conceptual, as opposed to syntactic processing. Both our combinatory and priming effects were early, onsetting between 100 and 150ms after picture onset and thus are likely to reflect the very earliest planning stages of a combinatory message

A diversity-oriented synthesis strategy enabling the combinatorial-type variation of macrocyclic peptidomimetic scaffolds† †Electronic supplementary information (ESI) available: Experimental procedures, characterization data and details of the computational analyses. See DOI: 10.1039/c5ob00371g Click here for additional data file.

Science.gov (United States)

Isidro-Llobet, Albert; Hadje Georgiou, Kathy; Galloway, Warren R. J. D.; Giacomini, Elisa; Hansen, Mette R.; Méndez-Abt, Gabriela; Tan, Yaw Sing; Carro, Laura; Sore, Hannah F.

2015-01-01

Macrocyclic peptidomimetics are associated with a broad range of biological activities. However, despite such potentially valuable properties, the macrocyclic peptidomimetic structural class is generally considered as being poorly explored within drug discovery. This has been attributed to the lack of general methods for producing collections of macrocyclic peptidomimetics with high levels of structural, and thus shape, diversity. In particular, there is a lack of scaffold diversity in current macrocyclic peptidomimetic libraries; indeed, the efficient construction of diverse molecular scaffolds presents a formidable general challenge to the synthetic chemist. Herein we describe a new, advanced strategy for the diversity-oriented synthesis (DOS) of macrocyclic peptidomimetics that enables the combinatorial variation of molecular scaffolds (core macrocyclic ring architectures). The generality and robustness of this DOS strategy is demonstrated by the step-efficient synthesis of a structurally diverse library of over 200 macrocyclic peptidomimetic compounds, each based around a distinct molecular scaffold and isolated in milligram quantities, from readily available building-blocks. To the best of our knowledge this represents an unprecedented level of scaffold diversity in a synthetically derived library of macrocyclic peptidomimetics. Cheminformatic analysis indicated that the library compounds access regions of chemical space that are distinct from those addressed by top-selling brand-name drugs and macrocyclic natural products, illustrating the value of our DOS approach to sample regions of chemical space underexploited in current drug discovery efforts. An analysis of three-dimensional molecular shapes illustrated that the DOS library has a relatively high level of shape diversity. PMID:25778821

An overview of strategies for synthetic modifications of aminoglycosides

International Nuclear Information System (INIS)

Aslam, M.W.

2013-01-01

Aminoglycosides, a family of structurally related broad-spectrum bactericidal compounds, have been used extensively for the treatment of aerobic gram-negative bacterial infections because of their rapid anti-bacterial activity, chemical stability and ability to work in combination with other drugs. However, toxic side-effects and growing bacterial resistance have narrowed the significance of aminoglycosides as antibiotics. Due to these limitations, extensive research on aminoglycosides has resulted in the development of a wide range of synthetic strategies to improve the overall characteristics of aminoglycosides. Herein, an overview of the various approaches reported in the literature to enhance binding affinity and to overcome resistance of aminoglycosides is provided. (author)

Rapid mapping of protein functional epitopes by combinatorial alanine scanning

OpenAIRE

Weiss, GA; Watanabe, CK; Zhong, A; Goddard, A; Sidhu, SS

2000-01-01

A combinatorial alanine-scanning strategy was used to determine simultaneously the functional contributions of 19 side chains buried at the interface between human growth hormone and the extracellular domain of its receptor. A phage-displayed protein library was constructed in which the 19 side chains were preferentially allowed to vary only as the wild type or alanine. The library pool was subjected to binding selections to isolate functional clones, and DNA sequencing was used to determine ...

Analysis and design of algorithms for combinatorial problems

CERN Document Server

Ausiello, G

1985-01-01

Combinatorial problems have been from the very beginning part of the history of mathematics. By the Sixties, the main classes of combinatorial problems had been defined. During that decade, a great number of research contributions in graph theory had been produced, which laid the foundations for most of the research in graph optimization in the following years. During the Seventies, a large number of special purpose models were developed. The impressive growth of this field since has been strongly determined by the demand of applications and influenced by the technological increases in computing power and the availability of data and software. The availability of such basic tools has led to the feasibility of the exact or well approximate solution of large scale realistic combinatorial optimization problems and has created a number of new combinatorial problems.

A binary plasmid system for shuffling combinatorial antibody libraries.

Science.gov (United States)

Collet, T A; Roben, P; O'Kennedy, R; Barbas, C F; Burton, D R; Lerner, R A

1992-11-01

We have used a binary system of replicon-compatible plasmids to test the potential for promiscuous recombination of heavy and light chains within sets of human Fab fragments isolated from combinatorial antibody libraries. Antibody molecules showed a surprising amount of promiscuity in that a particular heavy chain could recombine with multiple light chains with retention of binding to a protein antigen. The degree to which a given heavy chain productively paired with any light chain to bind antigen varied from 43% to 100% and depended strongly on the heavy-chain sequence. Such productive crosses resulted in a set of Fab fragments of similar apparent binding constants, which seemed to differ mainly in the amount of active Fab fragment produced in the bacterial cell. The dominance of the heavy chain in the antibody-antigen interaction was further explored in a set of directed crosses, in which heavy and light chains derived from antigen-specific clones were crossed with nonrelated heavy and light chains. In these crosses, an Fab fragment retained antigen binding only if it contained a heavy chain from an antigen-specific clone. In no case did the light chain confer detectable affinity when paired with indifferent heavy chains. The surprising promiscuity of heavy chains has ramifications for the evaluation of the diversity of combinatorial libraries made against protein antigens and should allow the combination of one such promiscuous heavy chain with an engineered light chain to form an Fab fragment carrying synthetic cofactors to assist in antibody catalysis.

Morphological Constraints on Cerebellar Granule Cell Combinatorial Diversity.

Science.gov (United States)

Gilmer, Jesse I; Person, Abigail L

2017-12-13

Combinatorial expansion by the cerebellar granule cell layer (GCL) is fundamental to theories of cerebellar contributions to motor control and learning. Granule cells (GrCs) sample approximately four mossy fiber inputs and are thought to form a combinatorial code useful for pattern separation and learning. We constructed a spatially realistic model of the cerebellar GCL and examined how GCL architecture contributes to GrC combinatorial diversity. We found that GrC combinatorial diversity saturates quickly as mossy fiber input diversity increases, and that this saturation is in part a consequence of short dendrites, which limit access to diverse inputs and favor dense sampling of local inputs. This local sampling also produced GrCs that were combinatorially redundant, even when input diversity was extremely high. In addition, we found that mossy fiber clustering, which is a common anatomical pattern, also led to increased redundancy of GrC input combinations. We related this redundancy to hypothesized roles of temporal expansion of GrC information encoding in service of learned timing, and we show that GCL architecture produces GrC populations that support both temporal and combinatorial expansion. Finally, we used novel anatomical measurements from mice of either sex to inform modeling of sparse and filopodia-bearing mossy fibers, finding that these circuit features uniquely contribute to enhancing GrC diversification and redundancy. Our results complement information theoretic studies of granule layer structure and provide insight into the contributions of granule layer anatomical features to afferent mixing. SIGNIFICANCE STATEMENT Cerebellar granule cells are among the simplest neurons, with tiny somata and, on average, just four dendrites. These characteristics, along with their dense organization, inspired influential theoretical work on the granule cell layer as a combinatorial expander, where each granule cell represents a unique combination of inputs

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.

Maximization of Tsallis entropy in the combinatorial formulation

International Nuclear Information System (INIS)

Suyari, Hiroki

2010-01-01

This paper presents the mathematical reformulation for maximization of Tsallis entropy S q in the combinatorial sense. More concretely, we generalize the original derivation of Maxwell-Boltzmann distribution law to Tsallis statistics by means of the corresponding generalized multinomial coefficient. Our results reveal that maximization of S 2-q under the usual expectation or S q under q-average using the escort expectation are naturally derived from the combinatorial formulations for Tsallis statistics with respective combinatorial dualities, that is, one for additive duality and the other for multiplicative duality.

Jack superpolynomials: physical and combinatorial definitions

International Nuclear Information System (INIS)

Desrosiers, P.; Mathieu, P.; Lapointe, L.

2004-01-01

Jack superpolynomials are eigenfunctions of the supersymmetric extension of the quantum trigonometric Calogero-Moser-Sutherland Hamiltonian. They are orthogonal with respect to the scalar product, dubbed physical, that is naturally induced by this quantum-mechanical problem. But Jack superpolynomials can also be defined more combinatorially, starting from the multiplicative bases of symmetric superpolynomials, enforcing orthogonality with respect to a one-parameter deformation of the combinatorial scalar product. Both constructions turn out to be equivalent. (author)

Torus actions, combinatorial topology, and homological algebra

International Nuclear Information System (INIS)

Bukhshtaber, V M; Panov, T E

2000-01-01

This paper is a survey of new results and open problems connected with fundamental combinatorial concepts, including polytopes, simplicial complexes, cubical complexes, and arrangements of subspaces. Attention is concentrated on simplicial and cubical subdivisions of manifolds, and especially on spheres. Important constructions are described that enable one to study these combinatorial objects by using commutative and homological algebra. The proposed approach to combinatorial problems is based on the theory of moment-angle complexes recently developed by the authors. The crucial construction assigns to each simplicial complex K with m vertices a T m -space Z K with special bigraded cellular decomposition. In the framework of this theory, well-known non-singular toric varieties arise as orbit spaces of maximally free actions of subtori on moment-angle complexes corresponding to simplicial spheres. It is shown that diverse invariants of simplicial complexes and related combinatorial-geometric objects can be expressed in terms of bigraded cohomology rings of the corresponding moment-angle complexes. Finally, it is shown that the new relationships between combinatorics, geometry, and topology lead to solutions of some well-known topological problems

Mixture-based combinatorial libraries from small individual peptide libraries: a case study on α1-antitrypsin deficiency.

Science.gov (United States)

Chang, Yi-Pin; Chu, Yen-Ho

2014-05-16

The design, synthesis and screening of diversity-oriented peptide libraries using a "libraries from libraries" strategy for the development of inhibitors of α1-antitrypsin deficiency are described. The major buttress of the biochemical approach presented here is the use of well-established solid-phase split-and-mix method for the generation of mixture-based libraries. The combinatorial technique iterative deconvolution was employed for library screening. While molecular diversity is the general consideration of combinatorial libraries, exquisite design through systematic screening of small individual libraries is a prerequisite for effective library screening and can avoid potential problems in some cases. This review will also illustrate how large peptide libraries were designed, as well as how a conformation-sensitive assay was developed based on the mechanism of the conformational disease. Finally, the combinatorially selected peptide inhibitor capable of blocking abnormal protein aggregation will be characterized by biophysical, cellular and computational methods.

Acquisition of a potent and selective TC-PTP inhibitor via a stepwise fluorophore-tagged combinatorial synthesis and screening strategy.

Science.gov (United States)

Zhang, Sheng; Chen, Lan; Luo, Yong; Gunawan, Andrea; Lawrence, David S; Zhang, Zhong-Yin

2009-09-16

Protein tyrosine phosphatases (PTPs) regulate a broad range of cellular processes including proliferation, differentiation, migration, apoptosis, and immune responses. Dysfunction of PTP activity is associated with cancers, metabolic syndromes, and autoimmune disorders. Consequently, small molecule PTP inhibitors should serve not only as powerful tools to delineate the physiological roles of these enzymes in vivo but also as lead compounds for therapeutic development. We describe a novel stepwise fluorophore-tagged combinatorial library synthesis and competitive fluorescence polarization screening approach that transforms a weak and general PTP inhibitor into an extremely potent and selective TC-PTP inhibitor with highly efficacious cellular activity. The result serves as a proof-of-concept in PTP inhibitor development, as it demonstrates the feasibility of acquiring potent, yet highly selective, cell permeable PTP inhibitory agents. Given the general nature of the approach, this strategy should be applicable to other PTP targets.

Combinatorial matrix theory

CERN Document Server

Mitjana, Margarida

2018-01-01

This book contains the notes of the lectures delivered at an Advanced Course on Combinatorial Matrix Theory held at Centre de Recerca Matemàtica (CRM) in Barcelona. These notes correspond to five series of lectures. The first series is dedicated to the study of several matrix classes defined combinatorially, and was delivered by Richard A. Brualdi. The second one, given by Pauline van den Driessche, is concerned with the study of spectral properties of matrices with a given sign pattern. Dragan Stevanović delivered the third one, devoted to describing the spectral radius of a graph as a tool to provide bounds of parameters related with properties of a graph. The fourth lecture was delivered by Stephen Kirkland and is dedicated to the applications of the Group Inverse of the Laplacian matrix. The last one, given by Ángeles Carmona, focuses on boundary value problems on finite networks with special in-depth on the M-matrix inverse problem.

Combinatorial identities for tenth order mock theta functions

Indian Academy of Sciences (India)

44

which lead us to one 4-way and one 3-way combinatorial identity. ... mock theta functions, partition identities and different combinatorial parameters, see for ... 3. Example 1.1. There are twelve (n + 1)–color partitions of 2: 21, 21 + 01, 11 + 11, ...

On the combinatorial foundations of Regge-calculus

International Nuclear Information System (INIS)

Budach, L.

1989-01-01

Lipschitz-Killing curvatures of piecewise flat spaces are combinatorial analogues of Lipschitz-Killing curvatures of Riemannian manifolds. In the following paper rigorous combinatorial representations and proofs of all basic results for Lipschitz-Killing curvatures not using analytic arguments are given. The principal tools for an elementary representation of Regge calculus can be developed by means of basic properties of dihedral angles. (author)

Combinatorial Speculations and the Combinatorial Conjecture for Mathematics

OpenAIRE

Mao, Linfan

2006-01-01

Combinatorics is a powerful tool for dealing with relations among objectives mushroomed in the past century. However, an more important work for mathematician is to apply combinatorics to other mathematics and other sciences not merely to find combinatorial behavior for objectives. Recently, such research works appeared on journals for mathematics and theoretical physics on cosmos. The main purpose of this paper is to survey these thinking and ideas for mathematics and cosmological physics, s...

Manipulating Combinatorial Structures.

Science.gov (United States)

Labelle, Gilbert

This set of transparencies shows how the manipulation of combinatorial structures in the context of modern combinatorics can easily lead to interesting teaching and learning activities at every level of education from elementary school to university. The transparencies describe: (1) the importance and relations of combinatorics to science and…

Some experience of shielding calculations by combinatorial method

International Nuclear Information System (INIS)

Korobejnikov, V.V.; Oussanov, V.I.

1996-01-01

Some aspects of the compound systems shielding calculations by a combinatorial approach are discussed. The effectiveness of such an approach is based on the fundamental characteristic of a compound system: if some element of the system have in itself mathematical or physical properties favorable for calculation, these properties may be used in a combinatorial approach and are lost when the system is being calculated in the whole by a direct approach. The combinatorial technique applied is well known. A compound system are being splitting for two or more auxiliary subsystems (so that calculation each of them is a more simple problem than calculation of the original problem (or at last is a soluble problem if original one is not). Calculation of every subsystem are carried out by suitable method and code, the coupling being made through boundary conditions or boundary source. The special consideration in the paper is given to a fast reactor shielding combinatorial analysis and to the testing of the results received. (author)

Synthetic Biology Open Language (SBOL) Version 2.2.0.

Science.gov (United States)

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

2018-04-02

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

Synthetic Biology Open Language (SBOL) Version 2.2.0

KAUST Repository

Cox, Robert Sidney

2018-04-04

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

Synthetic Biology Open Language (SBOL Version 2.2.0

Directory of Open Access Journals (Sweden)

Cox Robert Sidney

2018-04-01

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

Synthetic Biology Open Language (SBOL) Version 2.2.0

KAUST Repository

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

2018-01-01

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

Solid-Phase Synthesis of Small Molecule Libraries using Double Combinatorial Chemistry

DEFF Research Database (Denmark)

Nielsen, John; Jensen, Flemming R.

1997-01-01

The first synthesis of a combinatorial library using double combinatorial chemistry is presented. Coupling of unprotected Fmoc-tyrosine to the solid support was followed by Mitsunobu O-alkylation. Introduction of a diacid linker yields a system in which the double combinatorial step can be demons...

Accessing Specific Peptide Recognition by Combinatorial Chemistry

DEFF Research Database (Denmark)

Li, Ming

Molecular recognition is at the basis of all processes for life, and plays a central role in many biological processes, such as protein folding, the structural organization of cells and organelles, signal transduction, and the immune response. Hence, my PhD project is entitled “Accessing Specific...... Peptide Recognition by Combinatorial Chemistry”. Molecular recognition is a specific interaction between two or more molecules through noncovalent bonding, such as hydrogen bonding, metal coordination, van der Waals forces, π−π, hydrophobic, or electrostatic interactions. The association involves kinetic....... Combinatorial chemistry was invented in 1980s based on observation of functional aspects of the adaptive immune system. It was employed for drug development and optimization in conjunction with high-throughput synthesis and screening. (chapter 2) Combinatorial chemistry is able to rapidly produce many thousands...

Immune-Stimulating Combinatorial Therapy for Prostate Cancer

Science.gov (United States)

2016-10-01

Overlap: None 20 90061946 (Drake) Title: Epigenetic Drugs and Immuno Therapy for Prostate Cancer (EDIT-PC) Effort: 1.2 calendar months (10% effort...AWARD NUMBER: W81XWH-15-1-0667 TITLE: Immune-Stimulating Combinatorial Therapy for Prostate Cancer PRINCIPAL INVESTIGATOR: Robert Ivkov...Stimulating Combinatorial Therapy for Prostate Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-0667 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S

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)

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.

Frontiers in biomaterials the design, synthetic strategies and biocompatibility of polymer scaffolds for biomedical application

CERN Document Server

Cao, Shunsheng

2014-01-01

Frontiers in Biomaterials: The Design, Synthetic Strategies and Biocompatibility of Polymer Scaffolds for Biomedical Application, Volume 1" highlights the importance of biomaterials and their interaction with biological system. The need for the development of biomaterials as scaffold for tissue regeneration is driven by the increasing demands for materials that mimic functions of extracellular matrices of body tissues.This ebook covers the latest challenges on the biocompatibility of scaffold overtime after implantation and discusses the requirement of innovative technologies and strategies f

Infinitary Combinatory Reduction Systems

DEFF Research Database (Denmark)

Ketema, Jeroen; Simonsen, Jakob Grue

2011-01-01

We define infinitary Combinatory Reduction Systems (iCRSs), thus providing the first notion of infinitary higher-order rewriting. The systems defined are sufficiently general that ordinary infinitary term rewriting and infinitary ¿-calculus are special cases. Furthermore,we generalise a number...

Combinatorial Libraries of Bis-Heterocyclic Compounds with Skeletal Diversity

OpenAIRE

Soural, Miroslav; Bouillon, Isabelle; Krchňák, Viktor

2008-01-01

Combinatorial solid-phase synthesis of bis-heterocyclic compounds, characterized by the presence of two heterocyclic cores connected by a spacer of variable length/structure, provided structurally heterogeneous libraries with skeletal diversity. Both heterocyclic rings were assembled on resin in a combinatorial fashion.

Combinatorial Quantum Field Theory and Gluing Formula for Determinants

NARCIS (Netherlands)

Reshetikhin, N.; Vertman, B.

2015-01-01

We define the combinatorial Dirichlet-to-Neumann operator and establish a gluing formula for determinants of discrete Laplacians using a combinatorial Gaussian quantum field theory. In case of a diagonal inner product on cochains we provide an explicit local expression for the discrete

Automatic Design of Synthetic Gene Circuits through Mixed Integer Non-linear Programming

Science.gov (United States)

Huynh, Linh; Kececioglu, John; Köppe, Matthias; Tagkopoulos, Ilias

2012-01-01

Automatic design of synthetic gene circuits poses a significant challenge to synthetic biology, primarily due to the complexity of biological systems, and the lack of rigorous optimization methods that can cope with the combinatorial explosion as the number of biological parts increases. Current optimization methods for synthetic gene design rely on heuristic algorithms that are usually not deterministic, deliver sub-optimal solutions, and provide no guaranties on convergence or error bounds. Here, we introduce an optimization framework for the problem of part selection in synthetic gene circuits that is based on mixed integer non-linear programming (MINLP), which is a deterministic method that finds the globally optimal solution and guarantees convergence in finite time. Given a synthetic gene circuit, a library of characterized parts, and user-defined constraints, our method can find the optimal selection of parts that satisfy the constraints and best approximates the objective function given by the user. We evaluated the proposed method in the design of three synthetic circuits (a toggle switch, a transcriptional cascade, and a band detector), with both experimentally constructed and synthetic promoter libraries. Scalability and robustness analysis shows that the proposed framework scales well with the library size and the solution space. The work described here is a step towards a unifying, realistic framework for the automated design of biological circuits. PMID:22536398

Combinatorial Libraries of Bis-Heterocyclic Compounds with Skeletal Diversity

Science.gov (United States)

Soural, Miroslav; Bouillon, Isabelle; Krchňák, Viktor

2009-01-01

Combinatorial solid-phase synthesis of bis-heterocyclic compounds, characterized by the presence of two heterocyclic cores connected by a spacer of variable length/structure, provided structurally heterogeneous libraries with skeletal diversity. Both heterocyclic rings were assembled on resin in a combinatorial fashion. PMID:18811208

Combinatorial Cis-regulation in Saccharomyces Species

Directory of Open Access Journals (Sweden)

Aaron T. Spivak

2016-03-01

Full Text Available Transcriptional control of gene expression requires interactions between the cis-regulatory elements (CREs controlling gene promoters. We developed a sensitive computational method to identify CRE combinations with conserved spacing that does not require genome alignments. When applied to seven sensu stricto and sensu lato Saccharomyces species, 80% of the predicted interactions displayed some evidence of combinatorial transcriptional behavior in several existing datasets including: (1 chromatin immunoprecipitation data for colocalization of transcription factors, (2 gene expression data for coexpression of predicted regulatory targets, and (3 gene ontology databases for common pathway membership of predicted regulatory targets. We tested several predicted CRE interactions with chromatin immunoprecipitation experiments in a wild-type strain and strains in which a predicted cofactor was deleted. Our experiments confirmed that transcription factor (TF occupancy at the promoters of the CRE combination target genes depends on the predicted cofactor while occupancy of other promoters is independent of the predicted cofactor. Our method has the additional advantage of identifying regulatory differences between species. By analyzing the S. cerevisiae and S. bayanus genomes, we identified differences in combinatorial cis-regulation between the species and showed that the predicted changes in gene regulation explain several of the species-specific differences seen in gene expression datasets. In some instances, the same CRE combinations appear to regulate genes involved in distinct biological processes in the two different species. The results of this research demonstrate that (1 combinatorial cis-regulation can be inferred by multi-genome analysis and (2 combinatorial cis-regulation can explain differences in gene expression between species.

Conferences on Combinatorial and Additive Number Theory

CERN Document Server

2014-01-01

This proceedings volume is based on papers presented at the Workshops on Combinatorial and Additive Number Theory (CANT), which were held at the Graduate Center of the City University of New York in 2011 and 2012. The goal of the workshops is to survey recent progress in combinatorial number theory and related parts of mathematics. The workshop attracts researchers and students who discuss the state-of-the-art, open problems, and future challenges in number theory.

Fast Combinatorial Algorithm for the Solution of Linearly Constrained Least Squares Problems

Science.gov (United States)

Van Benthem, Mark H.; Keenan, Michael R.

2008-11-11

A fast combinatorial algorithm can significantly reduce the computational burden when solving general equality and inequality constrained least squares problems with large numbers of observation vectors. The combinatorial algorithm provides a mathematically rigorous solution and operates at great speed by reorganizing the calculations to take advantage of the combinatorial nature of the problems to be solved. The combinatorial algorithm exploits the structure that exists in large-scale problems in order to minimize the number of arithmetic operations required to obtain a solution.

Rationally reduced libraries for combinatorial pathway optimization minimizing experimental effort.

Science.gov (United States)

Jeschek, Markus; Gerngross, Daniel; Panke, Sven

2016-03-31

Rational flux design in metabolic engineering approaches remains difficult since important pathway information is frequently not available. Therefore empirical methods are applied that randomly change absolute and relative pathway enzyme levels and subsequently screen for variants with improved performance. However, screening is often limited on the analytical side, generating a strong incentive to construct small but smart libraries. Here we introduce RedLibs (Reduced Libraries), an algorithm that allows for the rational design of smart combinatorial libraries for pathway optimization thereby minimizing the use of experimental resources. We demonstrate the utility of RedLibs for the design of ribosome-binding site libraries by in silico and in vivo screening with fluorescent proteins and perform a simple two-step optimization of the product selectivity in the branched multistep pathway for violacein biosynthesis, indicating a general applicability for the algorithm and the proposed heuristics. We expect that RedLibs will substantially simplify the refactoring of synthetic metabolic pathways.

Simultaneous Disulfide and Boronic Acid Ester Exchange in Dynamic Combinatorial Libraries

Directory of Open Access Journals (Sweden)

Sanna L. Diemer

2015-09-01

Full Text Available Dynamic combinatorial chemistry has emerged as a promising tool for the discovery of complex receptors in supramolecular chemistry. At the heart of dynamic combinatorial chemistry are the reversible reactions that enable the exchange of building blocks between library members in dynamic combinatorial libraries (DCLs ensuring thermodynamic control over the system. If more than one reversible reaction operates in a single dynamic combinatorial library, the complexity of the system increases dramatically, and so does its possible applications. One can imagine two reversible reactions that operate simultaneously or two reversible reactions that operate independently. Both these scenarios have advantages and disadvantages. In this contribution, we show how disulfide exchange and boronic ester transesterification can function simultaneous in dynamic combinatorial libraries under appropriate conditions. We describe the detailed studies necessary to establish suitable reaction conditions and highlight the analytical techniques appropriate to study this type of system.

Combinatorial Micro-Macro Dynamical Systems

OpenAIRE

Diaz, Rafael; Villamarin, Sergio

2015-01-01

The second law of thermodynamics states that the entropy of an isolated system is almost always increasing. We propose combinatorial formalizations of the second law and explore their conditions of possibilities.

On Definitions and Existence of Combinatorial Entropy of 2d Fields

DEFF Research Database (Denmark)

Forchhammer, Søren Otto; Shtarkov, Yuri; Justesen, Jørn

1998-01-01

Different definitions of combinatorial entropy is presented and conditions for their existence examined.......Different definitions of combinatorial entropy is presented and conditions for their existence examined....

Fragment Linking and Optimization of Inhibitors of the Aspartic Protease Endothiapepsin : Fragment-Based Drug Design Facilitated by Dynamic Combinatorial Chemistry

NARCIS (Netherlands)

Mondal, Milon; Radeva, Nedyalka; Fanlo-Virgos, Hugo; Otto, Sijbren; Klebe, Gerhard; Hirsch, Anna K. H.

2016-01-01

Fragment-based drug design (FBDD) affords active compounds for biological targets. While there are numerous reports on FBDD by fragment growing/optimization, fragment linking has rarely been reported. Dynamic combinatorial chemistry (DCC) has become a powerful hit-identification strategy for

Enabling high performance computational science through combinatorial algorithms

International Nuclear Information System (INIS)

Boman, Erik G; Bozdag, Doruk; Catalyurek, Umit V; Devine, Karen D; Gebremedhin, Assefaw H; Hovland, Paul D; Pothen, Alex; Strout, Michelle Mills

2007-01-01

The Combinatorial Scientific Computing and Petascale Simulations (CSCAPES) Institute is developing algorithms and software for combinatorial problems that play an enabling role in scientific and engineering computations. Discrete algorithms will be increasingly critical for achieving high performance for irregular problems on petascale architectures. This paper describes recent contributions by researchers at the CSCAPES Institute in the areas of load balancing, parallel graph coloring, performance improvement, and parallel automatic differentiation

Enabling high performance computational science through combinatorial algorithms

Energy Technology Data Exchange (ETDEWEB)

Boman, Erik G [Discrete Algorithms and Math Department, Sandia National Laboratories (United States); Bozdag, Doruk [Biomedical Informatics, and Electrical and Computer Engineering, Ohio State University (United States); Catalyurek, Umit V [Biomedical Informatics, and Electrical and Computer Engineering, Ohio State University (United States); Devine, Karen D [Discrete Algorithms and Math Department, Sandia National Laboratories (United States); Gebremedhin, Assefaw H [Computer Science and Center for Computational Science, Old Dominion University (United States); Hovland, Paul D [Mathematics and Computer Science Division, Argonne National Laboratory (United States); Pothen, Alex [Computer Science and Center for Computational Science, Old Dominion University (United States); Strout, Michelle Mills [Computer Science, Colorado State University (United States)

2007-07-15

The Combinatorial Scientific Computing and Petascale Simulations (CSCAPES) Institute is developing algorithms and software for combinatorial problems that play an enabling role in scientific and engineering computations. Discrete algorithms will be increasingly critical for achieving high performance for irregular problems on petascale architectures. This paper describes recent contributions by researchers at the CSCAPES Institute in the areas of load balancing, parallel graph coloring, performance improvement, and parallel automatic differentiation.

Combinatorial Mathematics: Research into Practice

Science.gov (United States)

Sriraman, Bharath; English, Lyn D.

2004-01-01

Implications and suggestions for using combinatorial mathematics in the classroom through a survey and synthesis of numerous research studies are presented. The implications revolve around five major themes that emerge from analysis of these studies.

Neurite outgrowth induced by a synthetic peptide ligand of neural cell adhesion molecule requires fibroblast growth factor receptor activation

DEFF Research Database (Denmark)

Rønn, L C; Doherty, P; Holm, A

2000-01-01

identified a neuritogenic ligand, termed the C3 peptide, of the first immunoglobulin (lg) module of NCAM using a combinatorial library of synthetic peptides. Here we investigate whether stimulation of neurite outgrowth by this synthetic ligand of NCAM involves FGFRs. In primary cultures of cerebellar neurons...... from wild-type mice, the C3 peptide stimulated neurite outgrowth. This response was virtually absent in cultures of cerebellar neurons from transgenic mice expressing a dominant-negative form of the FGFR1. Likewise, in PC12E2 cells transiently expressing a dominant-negative form of the mouse FGFR1...

Combinatorial designs a tribute to Haim Hanani

CERN Document Server

Hartman, A

1989-01-01

Haim Hanani pioneered the techniques for constructing designs and the theory of pairwise balanced designs, leading directly to Wilson''s Existence Theorem. He also led the way in the study of resolvable designs, covering and packing problems, latin squares, 3-designs and other combinatorial configurations.The Hanani volume is a collection of research and survey papers at the forefront of research in combinatorial design theory, including Professor Hanani''s own latest work on Balanced Incomplete Block Designs. Other areas covered include Steiner systems, finite geometries, quasigroups, and t-designs.

A quark interpretation of the combinatorial hierarchy

International Nuclear Information System (INIS)

Enqvist, Kari.

1979-01-01

We propose a physical interpretation of the second level of the combinatorial hierarchy in terms of three quarks, three antiquarks and the vacuum. This interpretation allows us to introduce a new quantum number, which measures electromagnetic mass splitting of the quarks. We extend our argument by analogue to baryons, and find some SU(3) and some new mass formulas for baryons. The generalization of our approach to other hierarchy levels is discussed. We present also an empirical mass formula for baryons, which seems to be loosely connected with the combinatorial hierarchy. (author)

Combinatorial techniques to efficiently investigate and optimize organic thin film processing and properties.

Science.gov (United States)

Wieberger, Florian; Kolb, Tristan; Neuber, Christian; Ober, Christopher K; Schmidt, Hans-Werner

2013-04-08

In this article we present several developed and improved combinatorial techniques to optimize processing conditions and material properties of organic thin films. The combinatorial approach allows investigations of multi-variable dependencies and is the perfect tool to investigate organic thin films regarding their high performance purposes. In this context we develop and establish the reliable preparation of gradients of material composition, temperature, exposure, and immersion time. Furthermore we demonstrate the smart application of combinations of composition and processing gradients to create combinatorial libraries. First a binary combinatorial library is created by applying two gradients perpendicular to each other. A third gradient is carried out in very small areas and arranged matrix-like over the entire binary combinatorial library resulting in a ternary combinatorial library. Ternary combinatorial libraries allow identifying precise trends for the optimization of multi-variable dependent processes which is demonstrated on the lithographic patterning process. Here we verify conclusively the strong interaction and thus the interdependency of variables in the preparation and properties of complex organic thin film systems. The established gradient preparation techniques are not limited to lithographic patterning. It is possible to utilize and transfer the reported combinatorial techniques to other multi-variable dependent processes and to investigate and optimize thin film layers and devices for optical, electro-optical, and electronic applications.

Combinatorial Techniques to Efficiently Investigate and Optimize Organic Thin Film Processing and Properties

Directory of Open Access Journals (Sweden)

Hans-Werner Schmidt

2013-04-01

Full Text Available In this article we present several developed and improved combinatorial techniques to optimize processing conditions and material properties of organic thin films. The combinatorial approach allows investigations of multi-variable dependencies and is the perfect tool to investigate organic thin films regarding their high performance purposes. In this context we develop and establish the reliable preparation of gradients of material composition, temperature, exposure, and immersion time. Furthermore we demonstrate the smart application of combinations of composition and processing gradients to create combinatorial libraries. First a binary combinatorial library is created by applying two gradients perpendicular to each other. A third gradient is carried out in very small areas and arranged matrix-like over the entire binary combinatorial library resulting in a ternary combinatorial library. Ternary combinatorial libraries allow identifying precise trends for the optimization of multi-variable dependent processes which is demonstrated on the lithographic patterning process. Here we verify conclusively the strong interaction and thus the interdependency of variables in the preparation and properties of complex organic thin film systems. The established gradient preparation techniques are not limited to lithographic patterning. It is possible to utilize and transfer the reported combinatorial techniques to other multi-variable dependent processes and to investigate and optimize thin film layers and devices for optical, electro-optical, and electronic applications.

Asymmetric proteome equalization of the skeletal muscle proteome using a combinatorial hexapeptide library.

Directory of Open Access Journals (Sweden)

Jenny Rivers

Full Text Available Immobilized combinatorial peptide libraries have been advocated as a strategy for equalization of the dynamic range of a typical proteome. The technology has been applied predominantly to blood plasma and other biological fluids such as urine, but has not been used extensively to address the issue of dynamic range in tissue samples. Here, we have applied the combinatorial library approach to the equalization of a tissue where there is also a dramatic asymmetry in the range of abundances of proteins; namely, the soluble fraction of skeletal muscle. We have applied QconCAT and label-free methodology to the quantification of the proteins that bind to the beads as the loading is progressively increased. Although some equalization is achieved, and the most abundant proteins no longer dominate the proteome analysis, at high protein loadings a new asymmetry of protein expression is reached, consistent with the formation of complex assembles of heat shock proteins, cytoskeletal elements and other proteins on the beads. Loading at different ionic strength values leads to capture of different subpopulations of proteins, but does not completely eliminate the bias in protein accumulation. These assemblies may impair the broader utility of combinatorial library approaches to the equalization of tissue proteomes. However, the asymmetry in equalization is manifest at either low and high ionic strength values but manipulation of the solvent conditions may extend the capacity of the method.

Combinatorial Dyson-Schwinger equations and inductive data types

Science.gov (United States)

Kock, Joachim

2016-06-01

The goal of this contribution is to explain the analogy between combinatorial Dyson-Schwinger equations and inductive data types to a readership of mathematical physicists. The connection relies on an interpretation of combinatorial Dyson-Schwinger equations as fixpoint equations for polynomial functors (established elsewhere by the author, and summarised here), combined with the now-classical fact that polynomial functors provide semantics for inductive types. The paper is expository, and comprises also a brief introduction to type theory.

Solving the neutron diffusion equation on combinatorial geometry computational cells for reactor physics calculations

International Nuclear Information System (INIS)

Azmy, Y. Y.

2004-01-01

An approach is developed for solving the neutron diffusion equation on combinatorial geometry computational cells, that is computational cells composed by combinatorial operations involving simple-shaped component cells. The only constraint on the component cells from which the combinatorial cells are assembled is that they possess a legitimate discretization of the underlying diffusion equation. We use the Finite Difference (FD) approximation of the x, y-geometry diffusion equation in this work. Performing the same combinatorial operations involved in composing the combinatorial cell on these discrete-variable equations yields equations that employ new discrete variables defined only on the combinatorial cell's volume and faces. The only approximation involved in this process, beyond the truncation error committed in discretizing the diffusion equation over each component cell, is a consistent-order Legendre series expansion. Preliminary results for simple configurations establish the accuracy of the solution to the combinatorial geometry solution compared to straight FD as the system dimensions decrease. Furthermore numerical results validate the consistent Legendre-series expansion order by illustrating the second order accuracy of the combinatorial geometry solution, the same as standard FD. Nevertheless the magnitude of the error for the new approach is larger than FD's since it incorporates the additional truncated series approximation. (authors)

The Combinatorial Rigidity Conjecture is False for Cubic Polynomials

DEFF Research Database (Denmark)

Henriksen, Christian

2003-01-01

We show that there exist two cubic polynomials with connected Julia sets which are combinatorially equivalent but not topologically conjugate on their Julia sets. This disproves a conjecture by McMullen from 1995.......We show that there exist two cubic polynomials with connected Julia sets which are combinatorially equivalent but not topologically conjugate on their Julia sets. This disproves a conjecture by McMullen from 1995....

Combinatorial therapy of exercise-preconditioning and nanocurcumin formulation supplementation improves cardiac adaptation under hypobaric hypoxia.

Science.gov (United States)

Nehra, Sarita; Bhardwaj, Varun; Bansal, Anju; Saraswat, Deepika

2017-09-26

Chronic hypobaric hypoxia (cHH) mediated cardiac insufficiencies are associated with pathological damage. Sustained redox stress and work load are major causative agents of cardiac insufficiencies under cHH. Despite the advancements made in pharmacological (anti-oxidants, vasodilators) and non-pharmacological therapeutics (acclimatization strategies and schedules), only partial success has been achieved in improving cardiac acclimatization to cHH. This necessitates the need for potent combinatorial therapies to improve cardiac acclimatization at high altitudes. We hypothesize that a combinatorial therapy comprising preconditioning to mild aerobic treadmill exercise and supplementation with nanocurcumin formulation (NCF) consisting of nanocurcumin (NC) and pyrroloquinoline quinone (PQQ) might improve cardiac adaptation at high altitudes. Adult Sprague-Dawley rats pre-conditioned to treadmill exercise and supplemented with NCF were exposed to cHH (7620 m altitude corresponding to pO2~8% at 28±2°C, relative humidity 55%±1%) for 3 weeks. The rat hearts were analyzed for changes in markers of oxidative stress (free radical leakage, lipid peroxidation, manganese-superoxide dismutase [MnSOD] activity), cardiac injury (circulating cardiac troponin I [TnI] and T [cTnT], myocardial creatine kinase [CK-MB]), metabolic damage (lactate dehydrogenase [LDH] and acetyl-coenzyme A levels, lactate and pyruvate levels) and bio-energetic insufficiency (ATP, p-AMPKα). Significant modulations (p≤0.05) in cardiac redox status, metabolic damage, cardiac injury and bio-energetics were observed in rats receiving both NCF supplementation and treadmill exercise-preconditioning compared with rats receiving only one of the treatments. The combinatorial therapeutic strategy showed a tremendous improvement in cardiac acclimatization to cHH compared to either exercise-preconditioning or NCF supplementation alone which was evident from the effective modulation in redox, metabolic, contractile

Generating an Automated Test Suite by Variable Strength Combinatorial Testing for Web Services

Directory of Open Access Journals (Sweden)

Yin Li

2016-09-01

Full Text Available Testing Web Services has become the spotlight of software engineering as an important means to assure the quality of Web application. Due to lacking of graphic interface and source code, Web services need an automated testing method, which is an important part in efficiently designing and generating test suite. However, the existing testing methods may lead to the redundancy of test suite and the decrease of fault-detecting ability since it cannot handle scenarios where the strengths of the different interactions are not uniform. With the purpose of solving this problem, firstly the formal tree model based on WSDL is constructed and the actual interaction relationship of each node is made sufficient consideration into, then the combinatorial testing is proposed to generate variable strength combinatorial test suite based on One-test-at-a-time strategy. At last test cases are minimized according to constraint rules. The results show that compared with conventional random testing, the proposed approach can detect more errors with the same amount of test cases which turning out to be more ideal than existing ones in size.

The construction of combinatorial manifolds with prescribed sets of links of vertices

International Nuclear Information System (INIS)

Gaifullin, A A

2008-01-01

To every oriented closed combinatorial manifold we assign the set (with repetitions) of isomorphism classes of links of its vertices. The resulting transformation L is the main object of study in this paper. We pose an inversion problem for L and show that this problem is closely related to Steenrod's problem on the realization of cycles and to the Rokhlin-Schwartz-Thom construction of combinatorial Pontryagin classes. We obtain a necessary condition for a set of isomorphism classes of combinatorial spheres to belong to the image of L. (Sets satisfying this condition are said to be balanced.) We give an explicit construction showing that every balanced set of isomorphism classes of combinatorial spheres falls into the image of L after passing to a multiple set and adding several pairs of the form (Z,-Z), where -Z is the sphere Z with the orientation reversed. Given any singular simplicial cycle ξ of a space X, this construction enables us to find explicitly a combinatorial manifold M and a map φ:M→X such that φ * [M]=r[ξ] for some positive integer r. The construction is based on resolving singularities of ξ. We give applications of the main construction to cobordisms of manifolds with singularities and cobordisms of simple cells. In particular, we prove that every rational additive invariant of cobordisms of manifolds with singularities admits a local formula. Another application is the construction of explicit (though inefficient) local combinatorial formulae for polynomials in the rational Pontryagin classes of combinatorial manifolds

Dendrimer-based dynamic combinatorial libraries

NARCIS (Netherlands)

Chang, T.; Meijer, E.W.

2005-01-01

The aim of this project is to create water-sol. dynamic combinatorial libraries based upon dendrimer-guest complexes. The guest mols. are designed to bind to dendrimers using multiple secondary interactions, such as electrostatics and hydrogen bonding. We have been able to incorporate various guest

Computational Complexity of Combinatorial Surfaces

NARCIS (Netherlands)

Vegter, Gert; Yap, Chee K.

1990-01-01

We investigate the computational problems associated with combinatorial surfaces. Specifically, we present an algorithm (based on the Brahana-Dehn-Heegaard approach) for transforming the polygonal schema of a closed triangulated surface into its canonical form in O(n log n) time, where n is the

Combinatorial auctions for electronic business

Indian Academy of Sciences (India)

R. Narasimhan (Krishtel eMaging) 1461 1996 Oct 15 13:05:22

(6) Information feedback: An auction protocol may be a direct mechanism or an .... transparency of allocation decisions arise in resolving these ties. .... bidding, however more recently, combinatorial bids are allowed [50] making ...... Also, truth revelation and other game theoretic considerations are not taken into account.

Combinatorial Proofs and Algebraic Proofs

Indian Academy of Sciences (India)

Permanent link: https://www.ias.ac.in/article/fulltext/reso/018/07/0630-0645. Keywords. Combinatorial proof; algebraic proof; binomial identity; recurrence relation; composition; Fibonacci number; Fibonacci identity; Pascal triangle. Author Affiliations. Shailesh A Shirali1. Sahyadri School Tiwai Hill, Rajgurunagar Pune 410 ...

Polyhedral and semidefinite programming methods in combinatorial optimization

CERN Document Server

Tunçel, Levent

2010-01-01

Since the early 1960s, polyhedral methods have played a central role in both the theory and practice of combinatorial optimization. Since the early 1990s, a new technique, semidefinite programming, has been increasingly applied to some combinatorial optimization problems. The semidefinite programming problem is the problem of optimizing a linear function of matrix variables, subject to finitely many linear inequalities and the positive semidefiniteness condition on some of the matrix variables. On certain problems, such as maximum cut, maximum satisfiability, maximum stable set and geometric r

Paths and partitions: Combinatorial descriptions of the parafermionic states

Science.gov (United States)

Mathieu, Pierre

2009-09-01

The Zk parafermionic conformal field theories, despite the relative complexity of their modes algebra, offer the simplest context for the study of the bases of states and their different combinatorial representations. Three bases are known. The classic one is given by strings of the fundamental parafermionic operators whose sequences of modes are in correspondence with restricted partitions with parts at distance k -1 differing at least by 2. Another basis is expressed in terms of the ordered modes of the k -1 different parafermionic fields, which are in correspondence with the so-called multiple partitions. Both types of partitions have a natural (Bressoud) path representation. Finally, a third basis, formulated in terms of different paths, is inherited from the solution of the restricted solid-on-solid model of Andrews-Baxter-Forrester. The aim of this work is to review, in a unified and pedagogical exposition, these four different combinatorial representations of the states of the Zk parafermionic models. The first part of this article presents the different paths and partitions and their bijective relations; it is purely combinatorial, self-contained, and elementary; it can be read independently of the conformal-field-theory applications. The second part links this combinatorial analysis with the bases of states of the Zk parafermionic theories. With the prototypical example of the parafermionic models worked out in detail, this analysis contributes to fix some foundations for the combinatorial study of more complicated theories. Indeed, as we briefly indicate in ending, generalized versions of both the Bressoud and the Andrews-Baxter-Forrester paths emerge naturally in the description of the minimal models.

Combinatorial algebra syntax and semantics

CERN Document Server

Sapir, Mark V

2014-01-01

Combinatorial Algebra: Syntax and Semantics provides a comprehensive account of many areas of combinatorial algebra. It contains self-contained proofs of  more than 20 fundamental results, both classical and modern. This includes Golod–Shafarevich and Olshanskii's solutions of Burnside problems, Shirshov's solution of Kurosh's problem for PI rings, Belov's solution of Specht's problem for varieties of rings, Grigorchuk's solution of Milnor's problem, Bass–Guivarc'h theorem about the growth of nilpotent groups, Kleiman's solution of Hanna Neumann's problem for varieties of groups, Adian's solution of von Neumann-Day's problem, Trahtman's solution of the road coloring problem of Adler, Goodwyn and Weiss. The book emphasize several ``universal" tools, such as trees, subshifts, uniformly recurrent words, diagrams and automata.   With over 350 exercises at various levels of difficulty and with hints for the more difficult problems, this book can be used as a textbook, and aims to reach a wide and diversified...

Combinatorial methods for advanced materials research and development

Energy Technology Data Exchange (ETDEWEB)

Cremer, R.; Dondorf, S.; Hauck, M.; Horbach, D.; Kaiser, M.; Krysta, S.; Kyrylov, O.; Muenstermann, E.; Philipps, M.; Reichert, K.; Strauch, G. [Rheinisch-Westfaelische Technische Hochschule Aachen (Germany). Lehrstuhl fuer Theoretische Huettenkunde

2001-10-01

The applicability of combinatorial methods in developing advanced materials is illustrated presenting four examples for the deposition and characterization of one- and two-dimensionally laterally graded coatings, which were deposited by means of (reactive) magnetron sputtering and plasma-enhanced chemical vapor deposition. To emphasize the advantages of combinatorial approaches, metastable hard coatings like (Ti,Al)N and (Ti,Al,Hf)N respectively, as well as Ge-Sb-Te based films for rewritable optical data storage were investigated with respect to the relations between structure, composition, and the desired materials properties. (orig.)

Markov's theorem and algorithmically non-recognizable combinatorial manifolds

International Nuclear Information System (INIS)

Shtan'ko, M A

2004-01-01

We prove the theorem of Markov on the existence of an algorithmically non-recognizable combinatorial n-dimensional manifold for every n≥4. We construct for the first time a concrete manifold which is algorithmically non-recognizable. A strengthened form of Markov's theorem is proved using the combinatorial methods of regular neighbourhoods and handle theory. The proofs coincide for all n≥4. We use Borisov's group with insoluble word problem. It has two generators and twelve relations. The use of this group forms the base for proving the strengthened form of Markov's theorem

An Investigation into Post-Secondary Students' Understanding of Combinatorial Questions

Science.gov (United States)

Bulone, Vincent William

2017-01-01

The purpose of this dissertation was to study aspects of how post-secondary students understand combinatorial problems. Within this dissertation, I considered understanding through two different lenses: i) student connections to previous problems; and ii) common combinatorial distinctions such as ordered versus unordered and repetitive versus…

Design and spectroscopic reflectometry characterization of pulsed laser deposition combinatorial libraries

International Nuclear Information System (INIS)

Schenck, Peter K.; Bassim, Nabil D.; Otani, Makoto; Oguchi, Hiroyuki; Green, Martin L.

2007-01-01

The goal of the design of pulsed laser deposition (PLD) combinatorial library films is to optimize the compositional coverage of the films while maintaining a uniform thickness. The deposition pattern of excimer laser PLD films can be modeled with a bimodal cos n distribution. Deposited films were characterized using a spectroscopic reflectometer (250-1000 nm) to map the thickness of both single composition calibration films and combinatorial library films. These distribution functions were used to simulate the composition and thickness of multiple target combinatorial library films. The simulations were correlated with electron-probe microanalysis wavelength-dispersive spectroscopy (EPMA-WDS) composition maps. The composition and thickness of the library films can be fine-tuned by adjusting the laser spot size, fluence, background gas pressure, target geometry and other processing parameters which affect the deposition pattern. Results from compositionally graded combinatorial library films of the ternary system Al 2 O 3 -HfO 2 -Y 2 O 3 are discussed

A new evolutionary algorithm with LQV learning for combinatorial problems optimization

International Nuclear Information System (INIS)

Machado, Marcelo Dornellas; Schirru, Roberto

2000-01-01

Genetic algorithms are biologically motivated adaptive systems which have been used, with good results, for combinatorial problems optimization. In this work, a new learning mode, to be used by the population-based incremental learning algorithm, has the aim to build a new evolutionary algorithm to be used in optimization of numerical problems and combinatorial problems. This new learning mode uses a variable learning rate during the optimization process, constituting a process known as proportional reward. The development of this new algorithm aims its application in the optimization of reload problem of PWR nuclear reactors, in order to increase the useful life of the nuclear fuel. For the test, two classes of problems are used: numerical problems and combinatorial problems. Due to the fact that the reload problem is a combinatorial problem, the major interest relies on the last class. The results achieved with the tests indicate the applicability of the new learning mode, showing its potential as a developing tool in the solution of reload problem. (author)

Enumeration of Combinatorial Classes of Single Variable Complex Polynomial Vector Fields

DEFF Research Database (Denmark)

Dias, Kealey

A vector field in the space of degree d monic, centered single variable complex polynomial vector fields has a combinatorial structure which can be fully described by a combinatorial data set consisting of an equivalence relation and a marked subset on the integers mod 2d-2, satisfying certain...

An integrated evidence-based targeting strategy for determining combinatorial bioactive ingredients of a compound herbal medicine Qishen Yiqi dripping pills.

Science.gov (United States)

Zhang, Yiqian; Yu, Jiahui; Zhang, Wen; Wang, Yuewei; He, Yi; Zhou, Shuiping; Fan, Guanwei; Yang, Hua; Zhu, Yan; Li, Ping

2018-06-12

Qishen Yiqi is a widely used Chinese herbal medicine formula with "qi invigorating and blood activating" property. Its dripping pill preparation (QSYQ) is a commercial herbal medicine approved by the China Food and Drug Administration (CFDA) in 2003 and is extensively used clinically to treat cardiovascular diseases, such as ischemic heart failure and angina pectoris, as well as for the secondary prevention of myocardial infarction. However, the bioactive ingredients of QSYQ remain unclear. As QSYQ is a compound herbal formula, it is of great importance to elucidate its pharmacologically active ingredients and underlying synergetic effects. This experimental study was conducted to comprehensively determine the combinatorial bioactive ingredients (CBIs) in QSYQ and to elucidate their potential synergetic effects. The established strategy may shed new light on how to rapidly determine CBIs in complex herbal formulas with holistic properties. An integrated evidence-based targeting strategy was introduced and validated to determine CBIs in QSYQ. The strategy included the following steps: (1) Chemical ingredients in QSYQ were analyzed via UPLC-Q-TOF/MS in the negative and positive modes and were identified by comparison with standard compounds and previously reported data. Their potential therapeutic activities were predicted based on the ChEMBL database to preliminarily search for candidate bioactive ingredients, and their combination was defined as the CBIs. (2) The CBIs were directly trapped and prepared from QSYQ with a two-dimensional chromatographic separation system, and the remaining part was defined as the rest ingredients (RIs). (3) As animal and cell models, left anterior descending coronary artery ligation (LAD)-induced heart failure in rats and hypoxia-induced cardiac myocyte injury in H9c2 cells were applied to compare the potency of QSYQ, CBIs and RIs. (4) The synergetic effects on cardiac myocyte protection of multiple ingredients in CBIs were examined

Studies on Aculeines: Synthetic Strategy to the Fully Protected Protoaculeine B, the N-Terminal Amino Acid of Aculeine B.

Science.gov (United States)

Shiozaki, Hiroki; Miyahara, Masayoshi; Otsuka, Kazunori; Miyako, Kei; Honda, Akito; Takasaki, Yuichi; Takamizawa, Satoshi; Tukada, Hideyuki; Ishikawa, Yuichi; Sakai, Ryuichi; Oikawa, Masato

2018-05-23

A synthetic strategy for accessing protoaculeine B (1), the N-terminal amino acid of the highly modified peptide toxin aculeine, was developed via the synthesis of the fully protected natural homologue of 1 with a 12-mer poly(propanediamine). The synthesis of mono(propanediamine) analog 2, as well as core amino acid 3, was demonstrated by this strategy. New amino acid 3 induced convulsions in mice; however, compound 2 showed no such activity.

Emerging synthetic strategies for core cross-linked star (CCS) polymers and applications as interfacial stabilizers: bridging linear polymers and nanoparticles.

Science.gov (United States)

Chen, Qijing; Cao, Xueteng; Xu, Yuanyuan; An, Zesheng

2013-10-01

Core cross-linked star (CCS) polymers become increasingly important in polymer science and are evaluated in many value-added applications. However, limitations exist to varied degrees for different synthetic methods. It is clear that improvement in synthetic efficiency is fundamental in driving this field moving even further. Here, the most recent advances are highlighted in synthetic strategies, including cross-linking with cross-linkers of low solubility, polymerization-induced self-assembly in aqueous-based heterogeneous media, and cross-linking via dynamic covalent bonds. The understanding of CCS polymers is also further refined to advocate their role as an intermediate between linear polymers and polymeric nanoparticles, and their use as interfacial stabilizers is rationalized within this context. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Combinatorial vector fields and the valley structure of fitness landscapes.

Science.gov (United States)

Stadler, Bärbel M R; Stadler, Peter F

2010-12-01

Adaptive (downhill) walks are a computationally convenient way of analyzing the geometric structure of fitness landscapes. Their inherently stochastic nature has limited their mathematical analysis, however. Here we develop a framework that interprets adaptive walks as deterministic trajectories in combinatorial vector fields and in return associate these combinatorial vector fields with weights that measure their steepness across the landscape. We show that the combinatorial vector fields and their weights have a product structure that is governed by the neutrality of the landscape. This product structure makes practical computations feasible. The framework presented here also provides an alternative, and mathematically more convenient, way of defining notions of valleys, saddle points, and barriers in landscape. As an application, we propose a refined approximation for transition rates between macrostates that are associated with the valleys of the landscape.

Logging to Facilitate Combinatorial System Testing

NARCIS (Netherlands)

Kruse, P.M.; Prasetya, I.S.W.B.; Hage, J; Elyasov, Alexander

2014-01-01

Testing a web application is typically very complicated. Imposing simple coverage criteria such as function or line coverage is often not sufficient to uncover bugs due to incorrect components integration. Combinatorial testing can enforce a stronger criterion, while still allowing the

Combinatorial computational chemistry approach to the design of metal catalysts for deNOx

International Nuclear Information System (INIS)

Endou, Akira; Jung, Changho; Kusagaya, Tomonori; Kubo, Momoji; Selvam, Parasuraman; Miyamoto, Akira

2004-01-01

Combinatorial chemistry is an efficient technique for the synthesis and screening of a large number of compounds. Recently, we introduced the combinatorial approach to computational chemistry for catalyst design and proposed a new method called ''combinatorial computational chemistry''. In the present study, we have applied this combinatorial computational chemistry approach to the design of precious metal catalysts for deNO x . As the first step of the screening of the metal catalysts, we studied Rh, Pd, Ag, Ir, Pt, and Au clusters regarding the adsorption properties towards NO molecule. It was demonstrated that the energetically most stable adsorption state of NO on Ir model cluster, which was irrespective of both the shape and number of atoms including the model clusters

Balancing focused combinatorial libraries based on multiple GPCR ligands

Science.gov (United States)

Soltanshahi, Farhad; Mansley, Tamsin E.; Choi, Sun; Clark, Robert D.

2006-08-01

G-Protein coupled receptors (GPCRs) are important targets for drug discovery, and combinatorial chemistry is an important tool for pharmaceutical development. The absence of detailed structural information, however, limits the kinds of combinatorial design techniques that can be applied to GPCR targets. This is particularly problematic given the current emphasis on focused combinatorial libraries. By linking an incremental construction method (OptDesign) to the very fast shape-matching capability of ChemSpace, we have created an efficient method for designing targeted sublibraries that are topomerically similar to known actives. Multi-objective scoring allows consideration of multiple queries (actives) simultaneously. This can lead to a distribution of products skewed towards one particular query structure, however, particularly when the ligands of interest are quite dissimilar to one another. A novel pivoting technique is described which makes it possible to generate promising designs even under those circumstances. The approach is illustrated by application to some serotonergic agonists and chemokine antagonists.

The combinatorial derivation

Directory of Open Access Journals (Sweden)

Igor V. Protasov

2013-09-01

$\\Delta(A=\\{g\\in G:|gA\\cap A|=\\infty\\}$. The mapping $\\Delta:\\mathcal{P}_G\\rightarrow\\mathcal{P}_G$, $A\\mapsto\\Delta(A$, is called a combinatorial derivation and can be considered as an analogue of the topological derivation $d:\\mathcal{P}_X\\rightarrow\\mathcal{P}_X$, $A\\mapsto A^d$, where $X$ is a topological space and $A^d$ is the set of all limit points of $A$. Content: elementary properties, thin and almost thin subsets, partitions, inverse construction and $\\Delta$-trajectories,  $\\Delta$ and $d$.

Dynamic Combinatorial Chemistry

DEFF Research Database (Denmark)

Lisbjerg, Micke

This thesis is divided into seven chapters, which can all be read individually. The first chapter, however, contains a general introduction to the chemistry used in the remaining six chapters, and it is therefore recommended to read chapter one before reading the other chapters. Chapter 1...... is a general introductory chapter for the whole thesis. The history and concepts of dynamic combinatorial chemistry are described, as are some of the new and intriguing results recently obtained. Finally, the properties of a broad range of hexameric macrocycles are described in detail. Chapter 2 gives...

Multi-line split DNA synthesis: a novel combinatorial method to make high quality peptide libraries

Directory of Open Access Journals (Sweden)

Ueno Shingo

2004-09-01

Full Text Available Abstract Background We developed a method to make a various high quality random peptide libraries for evolutionary protein engineering based on a combinatorial DNA synthesis. Results A split synthesis in codon units was performed with mixtures of bases optimally designed by using a Genetic Algorithm program. It required only standard DNA synthetic reagents and standard DNA synthesizers in three lines. This multi-line split DNA synthesis (MLSDS is simply realized by adding a mix-and-split process to normal DNA synthesis protocol. Superiority of MLSDS method over other methods was shown. We demonstrated the synthesis of oligonucleotide libraries with 1016 diversity, and the construction of a library with random sequence coding 120 amino acids containing few stop codons. Conclusions Owing to the flexibility of the MLSDS method, it will be able to design various "rational" libraries by using bioinformatics databases.

A new strategy to deliver synthetic protein drugs: self-reproducible biologics using minicircles.

Science.gov (United States)

Yi, Hyoju; Kim, Youngkyun; Kim, Juryun; Jung, Hyerin; Rim, Yeri Alice; Jung, Seung Min; Park, Sung-Hwan; Ju, Ji Hyeon

2014-08-05

Biologics are the most successful drugs used in anticytokine therapy. However, they remain partially unsuccessful because of the elevated cost of their synthesis and purification. Development of novel biologics has also been hampered by the high cost. Biologics are made of protein components; thus, theoretically, they can be produced in vivo. Here we tried to invent a novel strategy to allow the production of synthetic drugs in vivo by the host itself. The recombinant minicircles encoding etanercept or tocilizumab, which are synthesized currently by pharmaceutical companies, were injected intravenously into animal models. Self-reproduced etanercept and tocilizumab were detected in the serum of mice. Moreover, arthritis subsided in mice that were injected with minicircle vectors carrying biologics. Self-reproducible biologics need neither factory facilities for drug production nor clinical processes, such as frequent drug injection. Although this novel strategy is in its very early conceptual stage, it seems to represent a potential alternative method for the delivery of biologics.

Some results from the combinatorial approach to quantum logic

International Nuclear Information System (INIS)

Greechie, R.J.

1976-01-01

The combinatorial approach to quantum logic focuses on certain interconnections between graphs, combinatorial designs, and convex sets as applied to a quantum logic. This article is concerned only with orthomodular lattices and associated structures. A class of complete atomic irreducible semimodular orthomodular lattices is derived which may not be represented as linear subspaces of a vector space over a division ring. Each of these lattices is a proposition system of dimension three. These proposition systems form orthocomplemented non-Desarguesian projective geometries. (B.R.H.)

Combinatorial enzyme technology for the conversion of agricultural fibers to functional properties

Science.gov (United States)

The concept of combinatorial chemistry has received little attention in agriculture and food research, although its applications in this area were described more than fifteen years ago (1, 2). More recently, interest in the use of combinatorial chemistry in agrochemical discovery has been revitalize...

DNA-Encoded Dynamic Combinatorial Chemical Libraries.

Science.gov (United States)

Reddavide, Francesco V; Lin, Weilin; Lehnert, Sarah; Zhang, Yixin

2015-06-26

Dynamic combinatorial chemistry (DCC) explores the thermodynamic equilibrium of reversible reactions. Its application in the discovery of protein binders is largely limited by difficulties in the analysis of complex reaction mixtures. DNA-encoded chemical library (DECL) technology allows the selection of binders from a mixture of up to billions of different compounds; however, experimental results often show low a signal-to-noise ratio and poor correlation between enrichment factor and binding affinity. Herein we describe the design and application of DNA-encoded dynamic combinatorial chemical libraries (EDCCLs). Our experiments have shown that the EDCCL approach can be used not only to convert monovalent binders into high-affinity bivalent binders, but also to cause remarkably enhanced enrichment of potent bivalent binders by driving their in situ synthesis. We also demonstrate the application of EDCCLs in DNA-templated chemical reactions. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Combinatorial synthesis of ceramic materials

Science.gov (United States)

Lauf, Robert J.; Walls, Claudia A.; Boatner, Lynn A.

2006-11-14

A combinatorial library includes a gelcast substrate defining a plurality of cavities in at least one surface thereof; and a plurality of gelcast test materials in the cavities, at least two of the test materials differing from the substrate in at least one compositional characteristic, the two test materials differing from each other in at least one compositional characteristic.

Combinatorial thin film materials science: From alloy discovery and optimization to alloy design

Energy Technology Data Exchange (ETDEWEB)

Gebhardt, Thomas, E-mail: gebhardt@mch.rwth-aachen.de; Music, Denis; Takahashi, Tetsuya; Schneider, Jochen M.

2012-06-30

This paper provides an overview of modern alloy development, from discovery and optimization towards alloy design, based on combinatorial thin film materials science. The combinatorial approach, combining combinatorial materials synthesis of thin film composition-spreads with high-throughput property characterization has proven to be a powerful tool to delineate composition-structure-property relationships, and hence to efficiently identify composition windows with enhanced properties. Furthermore, and most importantly for alloy design, theoretical models and hypotheses can be critically appraised. Examples for alloy discovery, optimization, and alloy design of functional as well as structural materials are presented. Using Fe-Mn based alloys as an example, we show that the combination of modern electronic-structure calculations with the highly efficient combinatorial thin film composition-spread method constitutes an effective tool for knowledge-based alloy design.

Combinatorial thin film materials science: From alloy discovery and optimization to alloy design

International Nuclear Information System (INIS)

Gebhardt, Thomas; Music, Denis; Takahashi, Tetsuya; Schneider, Jochen M.

2012-01-01

This paper provides an overview of modern alloy development, from discovery and optimization towards alloy design, based on combinatorial thin film materials science. The combinatorial approach, combining combinatorial materials synthesis of thin film composition-spreads with high-throughput property characterization has proven to be a powerful tool to delineate composition–structure–property relationships, and hence to efficiently identify composition windows with enhanced properties. Furthermore, and most importantly for alloy design, theoretical models and hypotheses can be critically appraised. Examples for alloy discovery, optimization, and alloy design of functional as well as structural materials are presented. Using Fe-Mn based alloys as an example, we show that the combination of modern electronic-structure calculations with the highly efficient combinatorial thin film composition-spread method constitutes an effective tool for knowledge-based alloy design.

Laguerre-type derivatives: Dobinski relations and combinatorial identities

International Nuclear Information System (INIS)

Penson, K. A.; Blasiak, P.; Horzela, A.; Duchamp, G. H. E.; Solomon, A. I.

2009-01-01

We consider properties of the operators D(r,M)=a r (a † a) M (which we call generalized Laguerre-type derivatives), with r=1,2,..., M=0,1,..., where a and a † are boson annihilation and creation operators, respectively, satisfying [a,a † ]=1. We obtain explicit formulas for the normally ordered form of arbitrary Taylor-expandable functions of D(r,M) with the help of an operator relation that generalizes the Dobinski formula. Coherent state expectation values of certain operator functions of D(r,M) turn out to be generating functions of combinatorial numbers. In many cases the corresponding combinatorial structures can be explicitly identified.

Distributing the computation in combinatorial optimization experiments over the cloud

OpenAIRE

Mario Brcic; Nikica Hlupic; Nenad Katanic

2017-01-01

Combinatorial optimization is an area of great importance since many of the real-world problems have discrete parameters which are part of the objective function to be optimized. Development of combinatorial optimization algorithms is guided by the empirical study of the candidate ideas and their performance over a wide range of settings or scenarios to infer general conclusions. Number of scenarios can be overwhelming, especially when modeling uncertainty in some of the problem’s parameters....

Quantum Resonance Approach to Combinatorial Optimization

Science.gov (United States)

Zak, Michail

1997-01-01

It is shown that quantum resonance can be used for combinatorial optimization. The advantage of the approach is in independence of the computing time upon the dimensionality of the problem. As an example, the solution to a constraint satisfaction problem of exponential complexity is demonstrated.

A Combinatorial Benders’ Cuts Algorithm for the Local Container Drayage Problem

Directory of Open Access Journals (Sweden)

Zhaojie Xue

2015-01-01

Full Text Available This paper examines the local container drayage problem under a special operation mode in which tractors and trailers can be separated; that is, tractors can be assigned to a new task at another location while trailers with containers are waiting for packing or unpacking. Meanwhile, the strategy of sharing empty containers between different customers is also considered to improve the efficiency and lower the operation cost. The problem is formulated as a vehicle routing and scheduling problem with temporal constraints. We adopt combinatorial benders’ cuts algorithm to solve this problem. Numerical experiments are performed on a group of randomly generated instances to test the performance of the proposed algorithm.

Combinatorial reasoning an introduction to the art of counting

CERN Document Server

DeTemple, Duane

2014-01-01

Written by well-known scholars in the field, this book introduces combinatorics alongside modern techniques, showcases the interdisciplinary aspects of the topic, and illustrates how to problem solve with a multitude of exercises throughout. The authors' approach is very reader-friendly and avoids the ""scholarly tone"" found in many books on this topic. Combinatorial Reasoning: An Introduction to the Art of Counting: Focuses on enumeration and combinatorial thinking as a way to develop a variety of effective approaches to solving counting problemsIncludes brief summaries of basic concepts f

Combinatorial interpretations of particular evaluations of complete and elementary symmetric functions

OpenAIRE

Mongelli, Pietro

2011-01-01

The Jacobi-Stirling numbers and the Legendre-Stirling numbers of the first and second kind were first introduced in [6], [7]. In this paper we note that Jacobi-Stirling numbers and Legendre-Stirling numbers are specializations of elementary and complete symmetric functions. We then study combinatorial interpretations of this specialization and obtain new combinatorial interpretations of the Jacobi-Stirling and Legendre-Stirling numbers.

Gian-Carlos Rota and Combinatorial Math.

Science.gov (United States)

Kolata, Gina Bari

1979-01-01

Presents the first of a series of occasional articles about mathematics as seen through the eyes of its prominent scholars. In an interview with Gian-Carlos Rota of the Massachusetts Institute of Technology he discusses how combinatorial mathematics began as a field and its future. (HM)

A Model of Students' Combinatorial Thinking

Science.gov (United States)

Lockwood, Elise

2013-01-01

Combinatorial topics have become increasingly prevalent in K-12 and undergraduate curricula, yet research on combinatorics education indicates that students face difficulties when solving counting problems. The research community has not yet addressed students' ways of thinking at a level that facilitates deeper understanding of how students…

Capability of focused Ar ion beam sputtering for combinatorial synthesis of metal films

International Nuclear Information System (INIS)

Nagata, T.; Haemori, M.; Chikyow, T.

2009-01-01

The authors examined the use of focused Ar ion beam sputtering (FAIS) for combinatorial synthesis. A Langmuir probe revealed that the electron temperature and density for FAIS of metal film deposition was lower than that of other major combinatorial thin film growth techniques such as pulsed laser deposition. Combining FAIS with the combinatorial method allowed the compositional fraction of the Pt-Ru binary alloy to be systematically controlled. Pt-Ru alloy metal film grew epitaxially on ZnO substrates, and crystal structures changed from the Pt phase (cubic structure) to the Ru phase (hexagonal structure) in the Pt-Ru alloy phase diagram. The alloy film has a smooth surface, with the Ru phase, in particular, showing a clear step-and-terrace structure. The combination of FAIS and the combinatorial method has major potential for the fabrication of high quality composition-spread metal film.

Capability of focused Ar ion beam sputtering for combinatorial synthesis of metal films

Energy Technology Data Exchange (ETDEWEB)

Nagata, T.; Haemori, M.; Chikyow, T. [Advanced Electric Materials Center, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044 (Japan)

2009-05-15

The authors examined the use of focused Ar ion beam sputtering (FAIS) for combinatorial synthesis. A Langmuir probe revealed that the electron temperature and density for FAIS of metal film deposition was lower than that of other major combinatorial thin film growth techniques such as pulsed laser deposition. Combining FAIS with the combinatorial method allowed the compositional fraction of the Pt-Ru binary alloy to be systematically controlled. Pt-Ru alloy metal film grew epitaxially on ZnO substrates, and crystal structures changed from the Pt phase (cubic structure) to the Ru phase (hexagonal structure) in the Pt-Ru alloy phase diagram. The alloy film has a smooth surface, with the Ru phase, in particular, showing a clear step-and-terrace structure. The combination of FAIS and the combinatorial method has major potential for the fabrication of high quality composition-spread metal film.

Algorithms in combinatorial design theory

CERN Document Server

Colbourn, CJ

1985-01-01

The scope of the volume includes all algorithmic and computational aspects of research on combinatorial designs. Algorithmic aspects include generation, isomorphism and analysis techniques - both heuristic methods used in practice, and the computational complexity of these operations. The scope within design theory includes all aspects of block designs, Latin squares and their variants, pairwise balanced designs and projective planes and related geometries.

Combinatorial optimization networks and matroids

CERN Document Server

Lawler, Eugene

2011-01-01

Perceptively written text examines optimization problems that can be formulated in terms of networks and algebraic structures called matroids. Chapters cover shortest paths, network flows, bipartite matching, nonbipartite matching, matroids and the greedy algorithm, matroid intersections, and the matroid parity problems. A suitable text or reference for courses in combinatorial computing and concrete computational complexity in departments of computer science and mathematics.

The triazine-based porous organic polymer: Novel synthetic strategy for high specific surface area

International Nuclear Information System (INIS)

Park, Jin Kuen

2017-01-01

A new type of microporous polymer has been successively synthesized via a simple polycondensation reaction with the 2,4-diaminotriazine moiety and dianhydride monomer. Diaminotriazine moieties in M1 especially can provide effective branching sites, resulting in high surface areas up to 1150 m"2 /g. In addition, the specific pore structure of the polyimide POP in its solid state can be modified by the surface activation method. Therefore, it can be expected that the resulting material will be a promising candidate for gas storage, and with this synthetic strategy, various type of derivatives will also be optimized

The triazine-based porous organic polymer: Novel synthetic strategy for high specific surface area

Energy Technology Data Exchange (ETDEWEB)

Park, Jin Kuen [Dept. of Chemistry, Hankuk University of Foreign Studies, Yongin (Korea, Republic of)

2017-02-15

A new type of microporous polymer has been successively synthesized via a simple polycondensation reaction with the 2,4-diaminotriazine moiety and dianhydride monomer. Diaminotriazine moieties in M1 especially can provide effective branching sites, resulting in high surface areas up to 1150 m{sup 2} /g. In addition, the specific pore structure of the polyimide POP in its solid state can be modified by the surface activation method. Therefore, it can be expected that the resulting material will be a promising candidate for gas storage, and with this synthetic strategy, various type of derivatives will also be optimized.

Summation on the basis of combinatorial representation of equal powers

Directory of Open Access Journals (Sweden)

Alexander I. Nikonov

2016-03-01

Full Text Available In the paper the conclusion of combinatorial expressions for the sums of members of several sequences is considered. Conclusion is made on the basis of combinatorial representation of the sum of the weighted equal powers. The weighted members of a geometrical progression, the simple arithmetic-geometrical and combined progressions are subject to summation. One of principal places in the given conclusion occupies representation of members of each of the specified progressions in the form of matrix elements. The row of this matrix is formed with use of a gang of equal powers with the set weight factor. Besides, in work formulas of combinatorial identities with participation of free components of the sums of equal powers, and also separate power-member of sequence of equal powers or a geometrical progression are presented. All presented formulas have the general basis-components of the sums of equal powers.

View Discovery in OLAP Databases through Statistical Combinatorial Optimization

Energy Technology Data Exchange (ETDEWEB)

Joslyn, Cliff A.; Burke, Edward J.; Critchlow, Terence J.

2009-05-01

The capability of OLAP database software systems to handle data complexity comes at a high price for analysts, presenting them a combinatorially vast space of views of a relational database. We respond to the need to deploy technologies sufficient to allow users to guide themselves to areas of local structure by casting the space of ``views'' of an OLAP database as a combinatorial object of all projections and subsets, and ``view discovery'' as an search process over that lattice. We equip the view lattice with statistical information theoretical measures sufficient to support a combinatorial optimization process. We outline ``hop-chaining'' as a particular view discovery algorithm over this object, wherein users are guided across a permutation of the dimensions by searching for successive two-dimensional views, pushing seen dimensions into an increasingly large background filter in a ``spiraling'' search process. We illustrate this work in the context of data cubes recording summary statistics for radiation portal monitors at US ports.

Validation of an Instrument and Testing Protocol for Measuring the Combinatorial Analysis Schema.

Science.gov (United States)

Staver, John R.; Harty, Harold

1979-01-01

Designs a testing situation to examine the presence of combinatorial analysis, to establish construct validity in the use of an instrument, Combinatorial Analysis Behavior Observation Scheme (CABOS), and to investigate the presence of the schema in young adolescents. (Author/GA)

MARCC (Matrix-Assisted Reader Chromatin Capture): an antibody-free method to enrich and analyze combinatorial nucleosome modifications

Science.gov (United States)

Su, Zhangli

2016-01-01

Combinatorial patterns of histone modifications are key indicators of different chromatin states. Most of the current approaches rely on the usage of antibodies to analyze combinatorial histone modifications. Here we detail an antibody-free method named MARCC (Matrix-Assisted Reader Chromatin Capture) to enrich combinatorial histone modifications. The combinatorial patterns are enriched on native nucleosomes extracted from cultured mammalian cells and prepared by micrococcal nuclease digestion. Such enrichment is achieved by recombinant chromatin-interacting protein modules, or so-called reader domains, which can bind in a combinatorial modification-dependent manner. The enriched chromatin can be quantified by western blotting or mass spectrometry for the co-existence of histone modifications, while the associated DNA content can be analyzed by qPCR or next-generation sequencing. Altogether, MARCC provides a reproducible, efficient and customizable solution to enrich and analyze combinatorial histone modifications. PMID:26131849

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

INdAM conference "CoMeTA 2013 - Combinatorial Methods in Topology and Algebra"

CERN Document Server

Delucchi, Emanuele; Moci, Luca

2015-01-01

Combinatorics plays a prominent role in contemporary mathematics, due to the vibrant development it has experienced in the last two decades and its many interactions with other subjects. This book arises from the INdAM conference "CoMeTA 2013 - Combinatorial Methods in Topology and Algebra,'' which was held in Cortona in September 2013. The event brought together emerging and leading researchers at the crossroads of Combinatorics, Topology and Algebra, with a particular focus on new trends in subjects such as: hyperplane arrangements; discrete geometry and combinatorial topology; polytope theory and triangulations of manifolds; combinatorial algebraic geometry and commutative algebra; algebraic combinatorics; and combinatorial representation theory. The book is divided into two parts. The first expands on the topics discussed at the conference by providing additional background and explanations, while the second presents original contributions on new trends in the topics addressed by the conference.

Combinatorial algebraic geometry selected papers from the 2016 apprenticeship program

CERN Document Server

Sturmfels, Bernd

2017-01-01

This volume consolidates selected articles from the 2016 Apprenticeship Program at the Fields Institute, part of the larger program on Combinatorial Algebraic Geometry that ran from July through December of 2016. Written primarily by junior mathematicians, the articles cover a range of topics in combinatorial algebraic geometry including curves, surfaces, Grassmannians, convexity, abelian varieties, and moduli spaces. This book bridges the gap between graduate courses and cutting-edge research by connecting historical sources, computation, explicit examples, and new results.

IκBα mediates prostate cancer cell death induced by combinatorial targeting of the androgen receptor

International Nuclear Information System (INIS)

Carter, Sarah Louise; Centenera, Margaret Mary; Tilley, Wayne Desmond; Selth, Luke Ashton; Butler, Lisa Maree

2016-01-01

Combining different clinical agents to target multiple pathways in prostate cancer cells, including androgen receptor (AR) signaling, is potentially an effective strategy to improve outcomes for men with metastatic disease. We have previously demonstrated that sub-effective concentrations of an AR antagonist, bicalutamide, and the histone deacetylase inhibitor, vorinostat, act synergistically when combined to cause death of AR-dependent prostate cancer cells. In this study, expression profiling of human prostate cancer cells treated with bicalutamide or vorinostat, alone or in combination, was employed to determine the molecular mechanisms underlying this synergistic action. Cell viability assays and quantitative real time PCR were used to validate identified candidate genes. A substantial proportion of the genes modulated by the combination of bicalutamide and vorinostat were androgen regulated. Independent pathway analysis identified further pathways and genes, most notably NFKBIA (encoding IκBα, an inhibitor of NF-κB and p53 signaling), as targets of this combinatorial treatment. Depletion of IκBα by siRNA knockdown enhanced apoptosis of prostate cancer cells, while ectopic overexpression of IκBα markedly suppressed cell death induced by the combination of bicalutamide and vorinostat. These findings implicate IκBα as a key mediator of the apoptotic action of this combinatorial AR targeting strategy and a promising new therapeutic target for prostate cancer. The online version of this article (doi:10.1186/s12885-016-2188-2) contains supplementary material, which is available to authorized users

Intracellular directed evolution of proteins from combinatorial libraries based on conditional phage replication.

Science.gov (United States)

Brödel, Andreas K; Jaramillo, Alfonso; Isalan, Mark

2017-09-01

Directed evolution is a powerful tool to improve the characteristics of biomolecules. Here we present a protocol for the intracellular evolution of proteins with distinct differences and advantages in comparison with established techniques. These include the ability to select for a particular function from a library of protein variants inside cells, minimizing undesired coevolution and propagation of nonfunctional library members, as well as allowing positive and negative selection logics using basally active promoters. A typical evolution experiment comprises the following stages: (i) preparation of a combinatorial M13 phagemid (PM) library expressing variants of the gene of interest (GOI) and preparation of the Escherichia coli host cells; (ii) multiple rounds of an intracellular selection process toward a desired activity; and (iii) the characterization of the evolved target proteins. The system has been developed for the selection of new orthogonal transcription factors (TFs) but is capable of evolving any gene-or gene circuit function-that can be linked to conditional M13 phage replication. Here we demonstrate our approach using as an example the directed evolution of the bacteriophage λ cI TF against two synthetic bidirectional promoters. The evolved TF variants enable simultaneous activation and repression against their engineered promoters and do not cross-react with the wild-type promoter, thus ensuring orthogonality. This protocol requires no special equipment, allowing synthetic biologists and general users to evolve improved biomolecules within ∼7 weeks.

PIPERIDINE OLIGOMERS AND COMBINATORIAL LIBRARIES THEREOF

DEFF Research Database (Denmark)

1999-01-01

The present invention relates to piperidine oligomers, methods for the preparation of piperidine oligomers and compound libraries thereof, and the use of piperidine oligomers as drug substances. The present invention also relates to the use of combinatorial libraries of piperidine oligomers...... in libraries (arrays) of compounds especially suitable for screening purposes....

The mathematics of a successful deconvolution: a quantitative assessment of mixture-based combinatorial libraries screened against two formylpeptide receptors.

Science.gov (United States)

Santos, Radleigh G; Appel, Jon R; Giulianotti, Marc A; Edwards, Bruce S; Sklar, Larry A; Houghten, Richard A; Pinilla, Clemencia

2013-05-30

In the past 20 years, synthetic combinatorial methods have fundamentally advanced the ability to synthesize and screen large numbers of compounds for drug discovery and basic research. Mixture-based libraries and positional scanning deconvolution combine two approaches for the rapid identification of specific scaffolds and active ligands. Here we present a quantitative assessment of the screening of 32 positional scanning libraries in the identification of highly specific and selective ligands for two formylpeptide receptors. We also compare and contrast two mixture-based library approaches using a mathematical model to facilitate the selection of active scaffolds and libraries to be pursued for further evaluation. The flexibility demonstrated in the differently formatted mixture-based libraries allows for their screening in a wide range of assays.

Three Syntactic Theories for Combinatory Graph Reduction

DEFF Research Database (Denmark)

Danvy, Olivier; Zerny, Ian

2011-01-01

in a third syntactic theory. The structure of the store-based abstract machine corresponding to this third syntactic theory oincides with that of Turner's original reduction machine. The three syntactic theories presented here The three syntactic heories presented here therefore have the following......We present a purely syntactic theory of graph reduction for the canonical combinators S, K, and I, where graph vertices are represented with evaluation contexts and let expressions. We express this syntactic theory as a reduction semantics, which we refocus into the first storeless abstract machine...... for combinatory graph reduction, which we refunctionalize into the first storeless natural semantics for combinatory graph reduction.We then factor out the introduction of let expressions to denote as many graph vertices as possible upfront instead of on demand, resulting in a second syntactic theory, this one...

Three Syntactic Theories for Combinatory Graph Reduction

DEFF Research Database (Denmark)

Danvy, Olivier; Zerny, Ian

2013-01-01

, as a store-based reduction semantics of combinatory term graphs. We then refocus this store-based reduction semantics into a store-based abstract machine. The architecture of this store-based abstract machine coincides with that of Turner's original reduction machine. The three syntactic theories presented......We present a purely syntactic theory of graph reduction for the canonical combinators S, K, and I, where graph vertices are represented with evaluation contexts and let expressions. We express this rst syntactic theory as a storeless reduction semantics of combinatory terms. We then factor out...... the introduction of let expressions to denote as many graph vertices as possible upfront instead of on demand . The factored terms can be interpreted as term graphs in the sense of Barendregt et al. We express this second syntactic theory, which we prove equivalent to the rst, as a storeless reduction semantics...

Quantum fields and processes a combinatorial approach

CERN Document Server

Gough, John

2018-01-01

Wick ordering of creation and annihilation operators is of fundamental importance for computing averages and correlations in quantum field theory and, by extension, in the Hudson-Parthasarathy theory of quantum stochastic processes, quantum mechanics, stochastic processes, and probability. This book develops the unified combinatorial framework behind these examples, starting with the simplest mathematically, and working up to the Fock space setting for quantum fields. Emphasizing ideas from combinatorics such as the role of lattice of partitions for multiple stochastic integrals by Wallstrom-Rota and combinatorial species by Joyal, it presents insights coming from quantum probability. It also introduces a 'field calculus' which acts as a succinct alternative to standard Feynman diagrams and formulates quantum field theory (cumulant moments, Dyson-Schwinger equation, tree expansions, 1-particle irreducibility) in this language. Featuring many worked examples, the book is aimed at mathematical physicists, quant...

Quantum fields and processes a combinatorial approach

CERN Document Server

Gough, John

2018-01-01

Wick ordering of creation and annihilation operators is of fundamental importance for computing averages and correlations in quantum field theory and, by extension, in the Hudson–Parthasarathy theory of quantum stochastic processes, quantum mechanics, stochastic processes, and probability. This book develops the unified combinatorial framework behind these examples, starting with the simplest mathematically, and working up to the Fock space setting for quantum fields. Emphasizing ideas from combinatorics such as the role of lattice of partitions for multiple stochastic integrals by Wallstrom–Rota and combinatorial species by Joyal, it presents insights coming from quantum probability. It also introduces a 'field calculus' which acts as a succinct alternative to standard Feynman diagrams and formulates quantum field theory (cumulant moments, Dyson–Schwinger equation, tree expansions, 1-particle irreducibility) in this language. Featuring many worked examples, the book is aimed at mathematical physicists,...

Tracking the emergence of synthetic biology.

Science.gov (United States)

Shapira, Philip; Kwon, Seokbeom; Youtie, Jan

2017-01-01

Synthetic biology is an emerging domain that combines biological and engineering concepts and which has seen rapid growth in research, innovation, and policy interest in recent years. This paper contributes to efforts to delineate this emerging domain by presenting a newly constructed bibliometric definition of synthetic biology. Our approach is dimensioned from a core set of papers in synthetic biology, using procedures to obtain benchmark synthetic biology publication records, extract keywords from these benchmark records, and refine the keywords, supplemented with articles published in dedicated synthetic biology journals. We compare our search strategy with other recent bibliometric approaches to define synthetic biology, using a common source of publication data for the period from 2000 to 2015. The paper details the rapid growth and international spread of research in synthetic biology in recent years, demonstrates that diverse research disciplines are contributing to the multidisciplinary development of synthetic biology research, and visualizes this by profiling synthetic biology research on the map of science. We further show the roles of a relatively concentrated set of research sponsors in funding the growth and trajectories of synthetic biology. In addition to discussing these analyses, the paper notes limitations and suggests lines for further work.

Combinatorial Algorithms for Computing Column Space Bases ThatHave Sparse Inverses

Energy Technology Data Exchange (ETDEWEB)

Pinar, Ali; Chow, Edmond; Pothen, Alex

2005-03-18

This paper presents a combinatorial study on the problem ofconstructing a sparse basis forthe null-space of a sparse, underdetermined, full rank matrix, A. Such a null-space is suitable forsolving solving many saddle point problems. Our approach is to form acolumn space basis of A that has a sparse inverse, by selecting suitablecolumns of A. This basis is then used to form a sparse null-space basisin fundamental form. We investigate three different algorithms forcomputing the column space basis: Two greedy approaches that rely onmatching, and a third employing a divide and conquer strategy implementedwith hypergraph partitioning followed by the greedy approach. We alsodiscuss the complexity of selecting a column basis when it is known thata block diagonal basis exists with a small given block size.

Log-balanced combinatorial sequences

Directory of Open Access Journals (Sweden)

Tomislav Došlic

2005-01-01

Full Text Available We consider log-convex sequences that satisfy an additional constraint imposed on their rate of growth. We call such sequences log-balanced. It is shown that all such sequences satisfy a pair of double inequalities. Sufficient conditions for log-balancedness are given for the case when the sequence satisfies a two- (or more- term linear recurrence. It is shown that many combinatorially interesting sequences belong to this class, and, as a consequence, that the above-mentioned double inequalities are valid for all of them.

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

Science.gov (United States)

Gilad, Assaf A; Shapiro, Mikhail G

2017-06-01

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

Specificity and combinatorial effects of Bacillus thuringiensis Cry toxins in the context of GMO environmental risk assessment

Directory of Open Access Journals (Sweden)

Angelika eHilbeck

2015-11-01

Full Text Available Stacked GM crops expressing up to six Cry toxins from Bacillus thuringiensis are today replacing the formerly grown single- transgene GM crop varieties. Stacking of multiple Cry toxins not only increase the environmental load of toxins but also raise the question on how possible interactions of the toxins can be assessed for risk assessment, which is mandatory for GM crops. However, no operational guidelines for a testing strategy or testing procedures exist. From the developers point of view, little data testing for combinatorial effects of Cry toxins is necessary as the range of affected organisms is focused on pest species and no evidence is claimed to exists pointing to combinatorial effects on nontarget organisms. We have examined this rationale critically using information reported in the scientific literature. To do so we address the hypothesis of narrow specificity of Cry toxins subdivided into three underlying different conceptual conditions i 'efficacy' in target pests as indicator for 'narrow specificity', ii lack of reported adverse effects of Cry toxins on nontarget organisms, and iii proposed modes of action of Cry toxins (or the lack thereof as mechanisms underlying the reported activity/efficacy/specificity of Cry toxins. Complementary to this information we evaluate reports about outcomes of combinatorial effect testing of Cry toxins in the scientific literature and relate those findings to the practice of the environmental risk assessment of Bt-corps in general and of stacked Bt-events in particular.

Novel Combinatorial Chemistry-Derived Inhibitors of Oncogenic Phosphatases

National Research Council Canada - National Science Library

Lazo, John

1999-01-01

Our overall goal of this US Army Breast Cancer Grant entitled "Novel Combinatorial Chemistry-Derived Inhibitors of Oncogenic Phosphatases" is to identity and develop novel therapeutic agents for human breast cancer...

Combinatorial Solid-Phase Synthesis of Balanol Analogues

DEFF Research Database (Denmark)

Nielsen, John; Lyngsø, Lars Ole

1996-01-01

The natural product balanol has served as a template for the design and synthesis of a combinatorial library using solid-phase chemistry. Using a retrosynthetic analysis, the structural analogues have been assembled from three relatively accessible building blocks. The solid-phase chemistry inclu...

Mitigation of Control Channel Jamming via Combinatorial Key Distribution

Science.gov (United States)

Falahati, Abolfazl; Azarafrooz, Mahdi

The problem of countering control channel jamming against internal adversaries in wireless ad hoc networks is addressed. Using combinatorial key distribution, a new method to secure the control channel access is introduced. This method, utilizes the established keys in the key establishment phase to hide the location of control channels without the need for a secure BS. This is in obtained by combination of a collision free one-way function and a combinatorial key establishment method. The proposed scheme can be considered as a special case of the ALOHA random access schemes which uses the common established keys as its seeds to generate the pattern of transmission.

On some interconnections between combinatorial optimization and extremal graph theory

Directory of Open Access Journals (Sweden)

Cvetković Dragoš M.

2004-01-01

Full Text Available The uniting feature of combinatorial optimization and extremal graph theory is that in both areas one should find extrema of a function defined in most cases on a finite set. While in combinatorial optimization the point is in developing efficient algorithms and heuristics for solving specified types of problems, the extremal graph theory deals with finding bounds for various graph invariants under some constraints and with constructing extremal graphs. We analyze by examples some interconnections and interactions of the two theories and propose some conclusions.

Functional completeness of the mixed λ-calculus and combinatory logic

DEFF Research Database (Denmark)

Nielson, Hanne Riis; Nielson, Flemming

1990-01-01

Functional completeness of the combinatory logic means that every lambda-expression may be translated into an equivalent combinator expression and this is the theoretical basis for the implementation of functional languages on combinator-based abstract machines. To obtain efficient implementations...... it is important to distinguish between early and late binding times, i.e. to distinguish between compile-time and run-time computations. The authors therefore introduce a two-level version of the lambda-calculus where this distinction is made in an explicit way. Turning to the combinatory logic they generate...

Gems of combinatorial optimization and graph algorithms

CERN Document Server

Skutella, Martin; Stiller, Sebastian; Wagner, Dorothea

2015-01-01

Are you looking for new lectures for your course on algorithms, combinatorial optimization, or algorithmic game theory?  Maybe you need a convenient source of relevant, current topics for a graduate student or advanced undergraduate student seminar?  Or perhaps you just want an enjoyable look at some beautiful mathematical and algorithmic results, ideas, proofs, concepts, and techniques in discrete mathematics and theoretical computer science?   Gems of Combinatorial Optimization and Graph Algorithms is a handpicked collection of up-to-date articles, carefully prepared by a select group of international experts, who have contributed some of their most mathematically or algorithmically elegant ideas.  Topics include longest tours and Steiner trees in geometric spaces, cartograms, resource buying games, congestion games, selfish routing, revenue equivalence and shortest paths, scheduling, linear structures in graphs, contraction hierarchies, budgeted matching problems, and motifs in networks.   This ...

Cryptographic Combinatorial Securities Exchanges

Science.gov (United States)

Thorpe, Christopher; Parkes, David C.

We present a useful new mechanism that facilitates the atomic exchange of many large baskets of securities in a combinatorial exchange. Cryptography prevents information about the securities in the baskets from being exploited, enhancing trust. Our exchange offers institutions who wish to trade large positions a new alternative to existing methods of block trading: they can reduce transaction costs by taking advantage of other institutions’ available liquidity, while third party liquidity providers guarantee execution—preserving their desired portfolio composition at all times. In our exchange, institutions submit encrypted orders which are crossed, leaving a “remainder”. The exchange proves facts about the portfolio risk of this remainder to third party liquidity providers without revealing the securities in the remainder, the knowledge of which could also be exploited. The third parties learn either (depending on the setting) the portfolio risk parameters of the remainder itself, or how their own portfolio risk would change if they were to incorporate the remainder into a portfolio they submit. In one setting, these third parties submit bids on the commission, and the winner supplies necessary liquidity for the entire exchange to clear. This guaranteed clearing, coupled with external price discovery from the primary markets for the securities, sidesteps difficult combinatorial optimization problems. This latter method of proving how taking on the remainder would change risk parameters of one’s own portfolio, without revealing the remainder’s contents or its own risk parameters, is a useful protocol of independent interest.

A combinatorial perspective of the protein inference problem.

Science.gov (United States)

Yang, Chao; He, Zengyou; Yu, Weichuan

2013-01-01

In a shotgun proteomics experiment, proteins are the most biologically meaningful output. The success of proteomics studies depends on the ability to accurately and efficiently identify proteins. Many methods have been proposed to facilitate the identification of proteins from peptide identification results. However, the relationship between protein identification and peptide identification has not been thoroughly explained before. In this paper, we devote ourselves to a combinatorial perspective of the protein inference problem. We employ combinatorial mathematics to calculate the conditional protein probabilities (protein probability means the probability that a protein is correctly identified) under three assumptions, which lead to a lower bound, an upper bound, and an empirical estimation of protein probabilities, respectively. The combinatorial perspective enables us to obtain an analytical expression for protein inference. Our method achieves comparable results with ProteinProphet in a more efficient manner in experiments on two data sets of standard protein mixtures and two data sets of real samples. Based on our model, we study the impact of unique peptides and degenerate peptides (degenerate peptides are peptides shared by at least two proteins) on protein probabilities. Meanwhile, we also study the relationship between our model and ProteinProphet. We name our program ProteinInfer. Its Java source code, our supplementary document and experimental results are available at: >http://bioinformatics.ust.hk/proteininfer.

Combinatorial biosynthesis of medicinal plant secondary metabolites

NARCIS (Netherlands)

Julsing, Mattijs K.; Koulman, Albert; Woerdenbag, Herman J.; Quax, Wim J.; Kayser, Oliver

2006-01-01

Combinatorial biosynthesis is a new tool in the generation of novel natural products and for the production of rare and expensive natural products. The basic concept is combining metabolic pathways in different organisms on a genetic level. As a consequence heterologous organisms provide precursors

Combinatorial aspects of covering arrays

Directory of Open Access Journals (Sweden)

Charles J. Colbourn

2004-11-01

Full Text Available Covering arrays generalize orthogonal arrays by requiring that t -tuples be covered, but not requiring that the appearance of t -tuples be balanced.Their uses in screening experiments has found application in software testing, hardware testing, and a variety of fields in which interactions among factors are to be identified. Here a combinatorial view of covering arrays is adopted, encompassing basic bounds, direct constructions, recursive constructions, algorithmic methods, and applications.

KENO-IV/CG, the combinatorial geometry version of the KENO Monte Carlo criticality safety program

International Nuclear Information System (INIS)

West, J.T.; Petrie, L.M.; Fraley, S.K.

1979-09-01

KENO-IV/CG was developed to merge the simple geometry input description utilized by combinatorial geometry with the repeating lattice feature of the original KENO geometry package. The result is a criticality code with the ability to model a complex system of repeating rectangular lattices inside a complicated three-dimensional geometry system. Furthermore, combinatorial geometry was modified to differentiate between combinatorial zones describing a particular KENO BOX to be repeated in a KENO array and those combinatorial zones describing geometry external to an array. This allows the user to maintain a simple coordinate system without any geometric conflict due to spatial overlap. Several difficult criticality design problems have been solved with the new geometry package in KENO-IV/CG, thus illustrating the power of the code to model difficult geometries with a minimum of effort

Phase Transitions in Combinatorial Optimization Problems Basics, Algorithms and Statistical Mechanics

CERN Document Server

Hartmann, Alexander K

2005-01-01

A concise, comprehensive introduction to the topic of statistical physics of combinatorial optimization, bringing together theoretical concepts and algorithms from computer science with analytical methods from physics. The result bridges the gap between statistical physics and combinatorial optimization, investigating problems taken from theoretical computing, such as the vertex-cover problem, with the concepts and methods of theoretical physics. The authors cover rapid developments and analytical methods that are both extremely complex and spread by word-of-mouth, providing all the necessary

Exploiting Quantum Resonance to Solve Combinatorial Problems

Science.gov (United States)

Zak, Michail; Fijany, Amir

2006-01-01

Quantum resonance would be exploited in a proposed quantum-computing approach to the solution of combinatorial optimization problems. In quantum computing in general, one takes advantage of the fact that an algorithm cannot be decoupled from the physical effects available to implement it. Prior approaches to quantum computing have involved exploitation of only a subset of known quantum physical effects, notably including parallelism and entanglement, but not including resonance. In the proposed approach, one would utilize the combinatorial properties of tensor-product decomposability of unitary evolution of many-particle quantum systems for physically simulating solutions to NP-complete problems (a class of problems that are intractable with respect to classical methods of computation). In this approach, reinforcement and selection of a desired solution would be executed by means of quantum resonance. Classes of NP-complete problems that are important in practice and could be solved by the proposed approach include planning, scheduling, search, and optimal design.

Combinatorial chemistry on solid support in the search for central nervous system agents.

Science.gov (United States)

Zajdel, Paweł; Pawłowski, Maciej; Martinez, Jean; Subra, Gilles

2009-08-01

The advent of combinatorial chemistry was one of the most important developments, that has significantly contributed to the drug discovery process. Within just a few years, its initial concept aimed at production of libraries containing huge number of compounds (thousands to millions), so called screening libraries, has shifted towards preparation of small and medium-sized rationally designed libraries. When applicable, the use of solid supports for the generation of libraries has been a real breakthrough in enhancing productivity. With a limited amount of resin and simple manual workups, the split/mix procedure may generate thousands of bead-tethered compounds. Beads can be chemically or physically encoded to facilitate the identification of a hit after the biological assay. Compartmentalization of solid supports using small reactors like teabags, kans or pellicular discrete supports like Lanterns resulted in powerful sort and combine technologies, relying on codes 'written' on the reactor, and thus reducing the need for automation and improving the number of compounds synthesized. These methods of solid-phase combinatorial chemistry have been recently supported by introduction of solid-supported reagents and scavenger resins. The first part of this review discusses the general premises of combinatorial chemistry and some methods used in the design of primary and focused combinatorial libraries. The aim of the second part is to present combinatorial chemistry methodologies aimed at discovering bioactive compounds acting on diverse GPCR involved in central nervous system disorders.

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

Science.gov (United States)

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

2017-08-09

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

Criticism of EFSA's scientific opinion on combinatorial effects of 'stacked' GM plants.

Science.gov (United States)

Bøhn, Thomas

2018-01-01

Recent genetically modified plants tend to include both insect resistance and herbicide tolerance traits. Some of these 'stacked' GM plants have multiple Cry-toxins expressed as well as tolerance to several herbicides. This means that non-target organisms in the environment (biodiversity) will be co-exposed to multiple stressors simultaneously. A similar co-exposure may happen to consumers through chemical residues in the food chain. EFSA, the responsible unit for minimizing risk of harm in European food chains, has expressed its scientific interest in combinatorial effects. However, when new data showed how two Cry-toxins acted in combination (added toxicity), and that the same Cry-toxins showed combinatorial effects when co-exposed with Roundup (Bøhn et al., 2016), EFSA dismissed these new peer-reviewed results. In effect, EFSA claimed that combinatorial effects are not relevant for itself. EFSA was justifying this by referring to a policy question, and by making invalid assumptions, which could have been checked directly with the lead-author. With such approach, EFSA may miss the opportunity to improve its environmental and health risk assessment of toxins and pesticides in the food chain. Failure to follow its own published requests for combinatorial effects research, may also risk jeopardizing EFSA's scientific and public reputation. Copyright © 2017. Published by Elsevier Ltd.

Beating Bias in the Directed Evolution of Proteins: Combining High-Fidelity on-Chip Solid-Phase Gene Synthesis with Efficient Gene Assembly for Combinatorial Library Construction.

Science.gov (United States)

Li, Aitao; Acevedo-Rocha, Carlos G; Sun, Zhoutong; Cox, Tony; Xu, Jia Lucy; Reetz, Manfred T

2018-02-02

Saturation mutagenesis (SM) constitutes a widely used technique in the directed evolution of selective enzymes as catalysts in organic chemistry and in the manipulation of metabolic paths and genomes, but the quality of the libraries is far from optimal due to the inherent amino acid bias. Herein, it is shown how this fundamental problem can be solved by applying high-fidelity solid-phase chemical gene synthesis on silicon chips followed by efficient gene assembly. Limonene epoxide hydrolase was chosen as the catalyst in the model desymmetrization of cyclohexene oxide with the stereoselective formation of (R,R)- and (S,S)-cyclohexane-1,2-diol. A traditional combinatorial PCR-based SM library, produced by simultaneous randomization at several residues by using a reduced amino acid alphabet, and the respective synthetic library were constructed and compared. Statistical analysis at the DNA level with massive sequencing demonstrates that, in the synthetic approach, 97 % of the theoretically possible DNA mutants are formed, whereas the traditional SM library contained only about 50 %. Screening at the protein level also showed the superiority of the synthetic library; many highly (R,R)- and (S,S)-selective variants being discovered are not found in the traditional SM library. With the prices of synthetic genes decreasing, this approach may point the way to future directed evolution. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthetic approaches to aromatic belts: building up strain in macrocyclic polyarenes.

Science.gov (United States)

Eisenberg, David; Shenhar, Roy; Rabinovitz, Mordecai

2010-08-01

This tutorial review discusses synthetic strategies towards aromatic belts, defined here as double-stranded conjugated macrocycles, such as [n]cyclacenes, [n]cyclophenacenes, Schlüter belt, and Vögtle belt. Their appeal stems, firstly, from the unique nature of their conjugation, having p orbitals oriented radially rather than perpendicular to the plane of the macrocycle. Secondly, as aromatic belts are model compounds of carbon nanotubes of different chiralities, a synthetic strategy towards the buildup of structural strain in these compounds could finally open a route towards rational chemical synthesis of carbon nanotubes. The elusiveness of these compounds has stimulated fascinating and ingenious synthetic strategies over the last decades. The various strategies are classified here by their approach to the buildup of structural strain, which is the main obstacle in the preparation of these curved polyarenes.

Combinatorial Clustering Algorithm of Quantum-Behaved Particle Swarm Optimization and Cloud Model

Directory of Open Access Journals (Sweden)

Mi-Yuan Shan

2013-01-01

Full Text Available We propose a combinatorial clustering algorithm of cloud model and quantum-behaved particle swarm optimization (COCQPSO to solve the stochastic problem. The algorithm employs a novel probability model as well as a permutation-based local search method. We are setting the parameters of COCQPSO based on the design of experiment. In the comprehensive computational study, we scrutinize the performance of COCQPSO on a set of widely used benchmark instances. By benchmarking combinatorial clustering algorithm with state-of-the-art algorithms, we can show that its performance compares very favorably. The fuzzy combinatorial optimization algorithm of cloud model and quantum-behaved particle swarm optimization (FCOCQPSO in vague sets (IVSs is more expressive than the other fuzzy sets. Finally, numerical examples show the clustering effectiveness of COCQPSO and FCOCQPSO clustering algorithms which are extremely remarkable.

Implementation of a combinatorial cleavage and deprotection scheme

DEFF Research Database (Denmark)

Nielsen, John; Rasmussen, Palle H.

1996-01-01

Phthalhydrazide libraries are synthesized in solution from substituted hydrazines and phthalimides in several different library formats including single compounds, indexed sub-libraries and a full library. When carried out during solid-phase synthesis, this combinatorial cleavage and deprotection...

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

Science.gov (United States)

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

2014-01-01

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

Combinatorial Optimization in Project Selection Using Genetic Algorithm

Science.gov (United States)

Dewi, Sari; Sawaluddin

2018-01-01

This paper discusses the problem of project selection in the presence of two objective functions that maximize profit and minimize cost and the existence of some limitations is limited resources availability and time available so that there is need allocation of resources in each project. These resources are human resources, machine resources, raw material resources. This is treated as a consideration to not exceed the budget that has been determined. So that can be formulated mathematics for objective function (multi-objective) with boundaries that fulfilled. To assist the project selection process, a multi-objective combinatorial optimization approach is used to obtain an optimal solution for the selection of the right project. It then described a multi-objective method of genetic algorithm as one method of multi-objective combinatorial optimization approach to simplify the project selection process in a large scope.

Evaluation of the Optimum Composition of Low-Temperature Fuel Cell Electrocatalysts for Methanol Oxidation by Combinatorial Screening.

Science.gov (United States)

Antolini, Ermete

2017-02-13

Combinatorial chemistry and high-throughput screening represent an innovative and rapid tool to prepare and evaluate a large number of new materials, saving time and expense for research and development. Considering that the activity and selectivity of catalysts depend on complex kinetic phenomena, making their development largely empirical in practice, they are prime candidates for combinatorial discovery and optimization. This review presents an overview of recent results of combinatorial screening of low-temperature fuel cell electrocatalysts for methanol oxidation. Optimum catalyst compositions obtained by combinatorial screening were compared with those of bulk catalysts, and the effect of the library geometry on the screening of catalyst composition is highlighted.

Combinatorial synthetic peptide vaccine strategy protects against hypervirulent CovR/S mutant streptococci

DEFF Research Database (Denmark)

Pandey, Manisha; Mortensen, Rasmus; Calcutt, Ainslie

2016-01-01

-mediated killing and enabling ingress of bacteria from a superficial wound to deep tissue.We previously showed that a combination vaccine incorporating J8-DT (conserved peptide vaccine from theM protein) and a recombinant SpyCEP fragment protects against CovR/S mutants. To enhance the vaccine's safety profile, we......), and it would be to the organism's advantage if the host did not induce a strong Ab response against it. However, S2 conjugated to diphtheria toxoid is highly immunogenic and induces Abs that recognize and neutralize SpyCEP. Hence, we describe a two-component peptide vaccine that induces Abs (anti-S2....... This protection correlated with a significant influx of neutrophils to the infection site. The data strongly suggest that the lack of natural immunity to hypervirulent GAS strains in humans could be rectified by this combination vaccine....

The Combinatorial Trace Method in Action

Science.gov (United States)

Krebs, Mike; Martinez, Natalie C.

2013-01-01

On any finite graph, the number of closed walks of length k is equal to the sum of the kth powers of the eigenvalues of any adjacency matrix. This simple observation is the basis for the combinatorial trace method, wherein we attempt to count (or bound) the number of closed walks of a given length so as to obtain information about the graph's…

Dynamic combinatorial chemistry at the phospholipid bilayer interface

NARCIS (Netherlands)

Mansfeld, Friederike M.; Au-Yeung, Ho Yu; Sanders, Jeremy K.M.; Otto, Sijbren

2010-01-01

Background: Molecular recognition at the environment provided by the phospholipid bilayer interface plays an important role in biology and is subject of intense investigation. Dynamic combinatorial chemistry is a powerful approach for exploring molecular recognition, but has thus far not been

Programme for test generation for combinatorial and sequential systems

International Nuclear Information System (INIS)

Tran Huy Hoan

1973-01-01

This research thesis reports the computer-assisted search for tests aimed at failure detection in combinatorial and sequential logic circuits. As he wants to deal with complex circuits with many modules such as those met in large scale integrated circuits (LSI), the author used propagation paths. He reports the development of a method which is valid for combinatorial systems and for several sequential circuits comprising elementary logic modules and JK and RS flip-flops. This method is developed on an IBM 360/91 computer in PL/1 language. The used memory space is limited and adjustable with respect to circuit dimension. Computing time is short when compared to that needed by other programmes. The solution is practical and efficient for failure test and localisation

Combinatorial nuclear level density by a Monte Carlo method

International Nuclear Information System (INIS)

Cerf, N.

1994-01-01

We present a new combinatorial method for the calculation of the nuclear level density. It is based on a Monte Carlo technique, in order to avoid a direct counting procedure which is generally impracticable for high-A nuclei. The Monte Carlo simulation, making use of the Metropolis sampling scheme, allows a computationally fast estimate of the level density for many fermion systems in large shell model spaces. We emphasize the advantages of this Monte Carlo approach, particularly concerning the prediction of the spin and parity distributions of the excited states,and compare our results with those derived from a traditional combinatorial or a statistical method. Such a Monte Carlo technique seems very promising to determine accurate level densities in a large energy range for nuclear reaction calculations

The Yoccoz Combinatorial Analytic Invariant

DEFF Research Database (Denmark)

Petersen, Carsten Lunde; Roesch, Pascale

2008-01-01

In this paper we develop a combinatorial analytic encoding of the Mandelbrot set M. The encoding is implicit in Yoccoz' proof of local connectivity of M at any Yoccoz parameter, i.e. any at most finitely renormalizable parameter for which all periodic orbits are repelling. Using this encoding we ...... to reprove that the dyadic veins of M are arcs and that more generally any two Yoccoz parameters are joined by a unique ruled (in the sense of Douady-Hubbard) arc in M....

Biocombinatorial Engineering of Fungal PKS-NRPS Hybrids for Production of Novel Synthetic Natural Products

DEFF Research Database (Denmark)

Nielsen, Maria Lund

encoding a PKS-NRPS hybrid responsible for the production of a medically relevant compound in Talaromyces atroroseus. To the best of my knowledge, this study represents the first example of reverse engineering of a Talaromyces species. In the fourth study (chapter 5), I used the CRISPR-Cas9 system...... structure optimization. Within the last decade, an alternative approach for expanding natural product chemodiversity has been applied. This strategy, known as combinatorial biosynthesis, involves the re-engineering of biosynthetic pathways and ultimately the rational engineering of new natural product...... analogs. This field, however, has proved very challenging and many engineering efforts have resulted in enzymatic loss-of-function or reduced yields. Thus, the future success in combinatorial biosynthetic studies requires a thorough understanding of the structure and function of biosynthetic enzymes...

A Robust and Versatile Method of Combinatorial Chemical Synthesis of Gene Libraries via Hierarchical Assembly of Partially Randomized Modules

Science.gov (United States)

Popova, Blagovesta; Schubert, Steffen; Bulla, Ingo; Buchwald, Daniela; Kramer, Wilfried

2015-01-01

A major challenge in gene library generation is to guarantee a large functional size and diversity that significantly increases the chances of selecting different functional protein variants. The use of trinucleotides mixtures for controlled randomization results in superior library diversity and offers the ability to specify the type and distribution of the amino acids at each position. Here we describe the generation of a high diversity gene library using tHisF of the hyperthermophile Thermotoga maritima as a scaffold. Combining various rational criteria with contingency, we targeted 26 selected codons of the thisF gene sequence for randomization at a controlled level. We have developed a novel method of creating full-length gene libraries by combinatorial assembly of smaller sub-libraries. Full-length libraries of high diversity can easily be assembled on demand from smaller and much less diverse sub-libraries, which circumvent the notoriously troublesome long-term archivation and repeated proliferation of high diversity ensembles of phages or plasmids. We developed a generally applicable software tool for sequence analysis of mutated gene sequences that provides efficient assistance for analysis of library diversity. Finally, practical utility of the library was demonstrated in principle by assessment of the conformational stability of library members and isolating protein variants with HisF activity from it. Our approach integrates a number of features of nucleic acids synthetic chemistry, biochemistry and molecular genetics to a coherent, flexible and robust method of combinatorial gene synthesis. PMID:26355961

Philosophy of Systems and Synthetic Biology

DEFF Research Database (Denmark)

Green, Sara

2017-01-01

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

Comprehensive human transcription factor binding site map for combinatory binding motifs discovery.

Directory of Open Access Journals (Sweden)

Arnoldo J Müller-Molina

Full Text Available To know the map between transcription factors (TFs and their binding sites is essential to reverse engineer the regulation process. Only about 10%-20% of the transcription factor binding motifs (TFBMs have been reported. This lack of data hinders understanding gene regulation. To address this drawback, we propose a computational method that exploits never used TF properties to discover the missing TFBMs and their sites in all human gene promoters. The method starts by predicting a dictionary of regulatory "DNA words." From this dictionary, it distills 4098 novel predictions. To disclose the crosstalk between motifs, an additional algorithm extracts TF combinatorial binding patterns creating a collection of TF regulatory syntactic rules. Using these rules, we narrowed down a list of 504 novel motifs that appear frequently in syntax patterns. We tested the predictions against 509 known motifs confirming that our system can reliably predict ab initio motifs with an accuracy of 81%-far higher than previous approaches. We found that on average, 90% of the discovered combinatorial binding patterns target at least 10 genes, suggesting that to control in an independent manner smaller gene sets, supplementary regulatory mechanisms are required. Additionally, we discovered that the new TFBMs and their combinatorial patterns convey biological meaning, targeting TFs and genes related to developmental functions. Thus, among all the possible available targets in the genome, the TFs tend to regulate other TFs and genes involved in developmental functions. We provide a comprehensive resource for regulation analysis that includes a dictionary of "DNA words," newly predicted motifs and their corresponding combinatorial patterns. Combinatorial patterns are a useful filter to discover TFBMs that play a major role in orchestrating other factors and thus, are likely to lock/unlock cellular functional clusters.

Isocyanide based multi component reactions in combinatorial chemistry.

NARCIS (Netherlands)

Dömling, A.

1998-01-01

Although usually regarded as a recent development, the combinatorial approach to the synthesis of libraries of new drug candidates was first described as early as 1961 using the isocyanide-based one-pot multicomponent Ugi reaction. Isocyanide-based multi component reactions (MCR's) markedly differ

View discovery in OLAP databases through statistical combinatorial optimization

Energy Technology Data Exchange (ETDEWEB)

Hengartner, Nick W [Los Alamos National Laboratory; Burke, John [PNNL; Critchlow, Terence [PNNL; Joslyn, Cliff [PNNL; Hogan, Emilie [PNNL

2009-01-01

OnLine Analytical Processing (OLAP) is a relational database technology providing users with rapid access to summary, aggregated views of a single large database, and is widely recognized for knowledge representation and discovery in high-dimensional relational databases. OLAP technologies provide intuitive and graphical access to the massively complex set of possible summary views available in large relational (SQL) structured data repositories. The capability of OLAP database software systems to handle data complexity comes at a high price for analysts, presenting them a combinatorially vast space of views of a relational database. We respond to the need to deploy technologies sufficient to allow users to guide themselves to areas of local structure by casting the space of 'views' of an OLAP database as a combinatorial object of all projections and subsets, and 'view discovery' as an search process over that lattice. We equip the view lattice with statistical information theoretical measures sufficient to support a combinatorial optimization process. We outline 'hop-chaining' as a particular view discovery algorithm over this object, wherein users are guided across a permutation of the dimensions by searching for successive two-dimensional views, pushing seen dimensions into an increasingly large background filter in a 'spiraling' search process. We illustrate this work in the context of data cubes recording summary statistics for radiation portal monitors at US ports.

Life by design: Philosophical perspectives on synthetic biology

Directory of Open Access Journals (Sweden)

Bensaude Vincent Bernadette

2015-01-01

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

Combinatorial Aspects of the Generalized Euler's Totient

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Nittiya Pabhapote

2010-01-01

Full Text Available A generalized Euler's totient is defined as a Dirichlet convolution of a power function and a product of the Souriau-Hsu-Möbius function with a completely multiplicative function. Two combinatorial aspects of the generalized Euler's totient, namely, its connections to other totients and its relations with counting formulae, are investigated.

ON 3-WAY COMBINATORIAL IDENTITIES A. K. AGARWAL MEGHA ...

Indian Academy of Sciences (India)

36

∗Corresponding author: Department of Basic and Applied Sciences, University College of Engineering,. Punjabi ... In this paper we provide combinatorial meanings to two generalized basic ... 2010 Mathematics Subject Classification. 05A15 ...

Exact model reduction of combinatorial reaction networks

Directory of Open Access Journals (Sweden)

Fey Dirk

2008-08-01

Full Text Available Abstract Background Receptors and scaffold proteins usually possess a high number of distinct binding domains inducing the formation of large multiprotein signaling complexes. Due to combinatorial reasons the number of distinguishable species grows exponentially with the number of binding domains and can easily reach several millions. Even by including only a limited number of components and binding domains the resulting models are very large and hardly manageable. A novel model reduction technique allows the significant reduction and modularization of these models. Results We introduce methods that extend and complete the already introduced approach. For instance, we provide techniques to handle the formation of multi-scaffold complexes as well as receptor dimerization. Furthermore, we discuss a new modeling approach that allows the direct generation of exactly reduced model structures. The developed methods are used to reduce a model of EGF and insulin receptor crosstalk comprising 5,182 ordinary differential equations (ODEs to a model with 87 ODEs. Conclusion The methods, presented in this contribution, significantly enhance the available methods to exactly reduce models of combinatorial reaction networks.

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.

Combinatorial structures and processing in neural blackboard architectures

NARCIS (Netherlands)

van der Velde, Frank; van der Velde, Frank; de Kamps, Marc; Besold, Tarek R.; d'Avila Garcez, Artur; Marcus, Gary F.; Miikkulainen, Risto

2015-01-01

We discuss and illustrate Neural Blackboard Architectures (NBAs) as the basis for variable binding and combinatorial processing the brain. We focus on the NBA for sentence structure. NBAs are based on the notion that conceptual representations are in situ, hence cannot be copied or transported.

Approaches for introducing high molecular diversity in scaffolds: fast parallel synthesis of highly substituted 1H-quinolin-4-one libraries.

Science.gov (United States)

Kuznetsov, Vladimir; Gorohovsky, Sofia; Levy, Amalia; Meir, Simcha; Shkoulev, Vladimir; Menashe, Naim; Greenwald, Moshe; Aizikovich, Alexander; Ofer, Dror; Byk, Gerardo; Gellerman, Garry

2004-01-01

We have developed a two steps strategy for the parallel synthesis of highly diversified quinolin-ones. In the first step we have combined and improved different synthetic methods for generating quinolin-4-ones bearing four different substitutions at specific positions using round bottomed flasks. The synthesis was assessed for a large number of substituted quinolin-4-ones. In the second step, the improved method was adapted to a parallel array synthesis using a 12 positions carrousel as demonstrated for the synthesis of 42-variable quinolin-4-ones. The first combinatorial library set 14(a-x) was obtained with a chemical purity of more than 95% without purification, the second library set 15(a-r), which included two synthetic steps, needed combinatorial purification using an innovative parallel purifier. The proposed approach contributes to a more extensive diversification of molecular scaffolds in general and provides access to highly substituted quinolinones in particular.

Concept of combinatorial de novo design of drug-like molecules by particle swarm optimization.

Science.gov (United States)

Hartenfeller, Markus; Proschak, Ewgenij; Schüller, Andreas; Schneider, Gisbert

2008-07-01

We present a fast stochastic optimization algorithm for fragment-based molecular de novo design (COLIBREE, Combinatorial Library Breeding). The search strategy is based on a discrete version of particle swarm optimization. Molecules are represented by a scaffold, which remains constant during optimization, and variable linkers and side chains. Different linkers represent virtual chemical reactions. Side-chain building blocks were obtained from pseudo-retrosynthetic dissection of large compound databases. Here, ligand-based design was performed using chemically advanced template search (CATS) topological pharmacophore similarity to reference ligands as fitness function. A weighting scheme was included for particle swarm optimization-based molecular design, which permits the use of many reference ligands and allows for positive and negative design to be performed simultaneously. In a case study, the approach was applied to the de novo design of potential peroxisome proliferator-activated receptor subtype-selective agonists. The results demonstrate the ability of the technique to cope with large combinatorial chemistry spaces and its applicability to focused library design. The technique was able to perform exploitation of a known scheme and at the same time explorative search for novel ligands within the framework of a given molecular core structure. It thereby represents a practical solution for compound screening in the early hit and lead finding phase of a drug discovery project.

Combinatorial development of antibacterial Zr-Cu-Al-Ag thin film metallic glasses.

Science.gov (United States)

Liu, Yanhui; Padmanabhan, Jagannath; Cheung, Bettina; Liu, Jingbei; Chen, Zheng; Scanley, B Ellen; Wesolowski, Donna; Pressley, Mariyah; Broadbridge, Christine C; Altman, Sidney; Schwarz, Udo D; Kyriakides, Themis R; Schroers, Jan

2016-05-27

Metallic alloys are normally composed of multiple constituent elements in order to achieve integration of a plurality of properties required in technological applications. However, conventional alloy development paradigm, by sequential trial-and-error approach, requires completely unrelated strategies to optimize compositions out of a vast phase space, making alloy development time consuming and labor intensive. Here, we challenge the conventional paradigm by proposing a combinatorial strategy that enables parallel screening of a multitude of alloys. Utilizing a typical metallic glass forming alloy system Zr-Cu-Al-Ag as an example, we demonstrate how glass formation and antibacterial activity, two unrelated properties, can be simultaneously characterized and the optimal composition can be efficiently identified. We found that in the Zr-Cu-Al-Ag alloy system fully glassy phase can be obtained in a wide compositional range by co-sputtering, and antibacterial activity is strongly dependent on alloy compositions. Our results indicate that antibacterial activity is sensitive to Cu and Ag while essentially remains unchanged within a wide range of Zr and Al. The proposed strategy not only facilitates development of high-performing alloys, but also provides a tool to unveil the composition dependence of properties in a highly parallel fashion, which helps the development of new materials by design.

Random vs. Combinatorial Methods for Discrete Event Simulation of a Grid Computer Network

Science.gov (United States)

Kuhn, D. Richard; Kacker, Raghu; Lei, Yu

2010-01-01

This study compared random and t-way combinatorial inputs of a network simulator, to determine if these two approaches produce significantly different deadlock detection for varying network configurations. Modeling deadlock detection is important for analyzing configuration changes that could inadvertently degrade network operations, or to determine modifications that could be made by attackers to deliberately induce deadlock. Discrete event simulation of a network may be conducted using random generation, of inputs. In this study, we compare random with combinatorial generation of inputs. Combinatorial (or t-way) testing requires every combination of any t parameter values to be covered by at least one test. Combinatorial methods can be highly effective because empirical data suggest that nearly all failures involve the interaction of a small number of parameters (1 to 6). Thus, for example, if all deadlocks involve at most 5-way interactions between n parameters, then exhaustive testing of all n-way interactions adds no additional information that would not be obtained by testing all 5-way interactions. While the maximum degree of interaction between parameters involved in the deadlocks clearly cannot be known in advance, covering all t-way interactions may be more efficient than using random generation of inputs. In this study we tested this hypothesis for t = 2, 3, and 4 for deadlock detection in a network simulation. Achieving the same degree of coverage provided by 4-way tests would have required approximately 3.2 times as many random tests; thus combinatorial methods were more efficient for detecting deadlocks involving a higher degree of interactions. The paper reviews explanations for these results and implications for modeling and simulation.

Bioinspired computation in combinatorial optimization: algorithms and their computational complexity

DEFF Research Database (Denmark)

Neumann, Frank; Witt, Carsten

2012-01-01

Bioinspired computation methods, such as evolutionary algorithms and ant colony optimization, are being applied successfully to complex engineering and combinatorial optimization problems, and it is very important that we understand the computational complexity of these algorithms. This tutorials...... problems. Classical single objective optimization is examined first. They then investigate the computational complexity of bioinspired computation applied to multiobjective variants of the considered combinatorial optimization problems, and in particular they show how multiobjective optimization can help...... to speed up bioinspired computation for single-objective optimization problems. The tutorial is based on a book written by the authors with the same title. Further information about the book can be found at www.bioinspiredcomputation.com....

Immobilization of N-Heterocyclic Carbene Compounds: A Synthetic Perspective.

Science.gov (United States)

Zhong, Rui; Lindhorst, Anja C; Groche, Florian J; Kühn, Fritz E

2017-02-08

Over the course of the past 15 years the success story of N-heterocyclic carbene (NHC) compounds in organic, inorganic, and organometallic chemistry has been extended to another dimension. The immobilization of NHC compounds, undergoing continuous diversification, broadens their range of applications and leads to new solutions for challenges in catalytic and synthetic chemistry. This review intends to present a synthetic toolkit for the immobilization of NHC compounds, giving the reader an overview on synthetic techniques and strategies available in the literature. By individually summarizing and assessing the synthetic steps of the immobilization process, a comprehensive picture of the strategies and methodologies for the immobilization of NHC compounds is presented. Furthermore, the characterization of supported NHC compounds is discussed in detail in order to set up necessary criteria for an in-depth analysis of the immobilized derivatives. Finally, the catalytic applications of immobilized NHC compounds are briefly reviewed to illustrate the practical use of this technique for a broad variety of reaction types.

Advanced Aqueous Phase Catalyst Development using Combinatorial Methods, Phase II

Data.gov (United States)

National Aeronautics and Space Administration — Combinatorial methods are proposed to develop advanced Aqueous Oxidation Catalysts (AOCs) with the capability to mineralize organic contaminants present in effluents...

Synthetic Genetic Targeting of Genome Instability in Cancer

International Nuclear Information System (INIS)

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

2013-01-01

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

Device for preparing combinatorial libraries in powder metallurgy.

Science.gov (United States)

Yang, Shoufeng; Evans, Julian R G

2004-01-01

This paper describes a powder-metering, -mixing, and -dispensing mechanism that can be used as a method for producing large numbers of samples for metallurgical evaluation or electrical or mechanical testing from multicomponent metal and cermet powder systems. It is designed to make use of the same commercial powders that are used in powder metallurgy and, therefore, to produce samples that are faithful to the microstructure of finished products. The particle assemblies produced by the device could be consolidated by die pressing, isostatic pressing, laser sintering, or direct melting. The powder metering valve provides both on/off and flow rate control of dry powders in open capillaries using acoustic vibration. The valve is simple and involves no relative movement, avoiding seizure with fine powders. An orchestra of such valves can be arranged on a building platform to prepare multicomponent combinatorial libraries. As with many combinatorial devices, identification and evaluation of sources of mixing error as a function of sample size is mandatory. Such an analysis is presented.

Non-unique factorizations algebraic, combinatorial and analytic theory

CERN Document Server

Geroldinger, Alfred

2006-01-01

From its origins in algebraic number theory, the theory of non-unique factorizations has emerged as an independent branch of algebra and number theory. Focused efforts over the past few decades have wrought a great number and variety of results. However, these remain dispersed throughout the vast literature. For the first time, Non-Unique Factorizations: Algebraic, Combinatorial, and Analytic Theory offers a look at the present state of the theory in a single, unified resource.Taking a broad look at the algebraic, combinatorial, and analytic fundamentals, this book derives factorization results and applies them in concrete arithmetical situations using appropriate transfer principles. It begins with a basic introduction that can be understood with knowledge of standard basic algebra. The authors then move to the algebraic theory of monoids, arithmetic theory of monoids, the structure of sets of lengths, additive group theory, arithmetical invariants, and the arithmetic of Krull monoids. They also provide a s...

Probabilistic methods in combinatorial analysis

CERN Document Server

Sachkov, Vladimir N

2014-01-01

This 1997 work explores the role of probabilistic methods for solving combinatorial problems. These methods not only provide the means of efficiently using such notions as characteristic and generating functions, the moment method and so on but also let us use the powerful technique of limit theorems. The basic objects under investigation are nonnegative matrices, partitions and mappings of finite sets, with special emphasis on permutations and graphs, and equivalence classes specified on sequences of finite length consisting of elements of partially ordered sets; these specify the probabilist

Steam explosion and its combinatorial pretreatment refining technology of plant biomass to bio-based products.

Science.gov (United States)

Chen, Hong-Zhang; Liu, Zhi-Hua

2015-06-01

Pretreatment is a key unit operation affecting the refinery efficiency of plant biomass. However, the poor efficiency of pretreatment and the lack of basic theory are the main challenges to the industrial implementation of the plant biomass refinery. The purpose of this work is to review steam explosion and its combinatorial pretreatment as a means of overcoming the intrinsic characteristics of plant biomass, including recalcitrance, heterogeneity, multi-composition, and diversity. The main advantages of the selective use of steam explosion and other combinatorial pretreatments across the diversity of raw materials are introduced. Combinatorial pretreatment integrated with other unit operations is proposed as a means to exploit the high-efficiency production of bio-based products from plant biomass. Finally, several pilot- and demonstration-scale operations of the plant biomass refinery are described. Based on the principle of selective function and structure fractionation, and multi-level and directional composition conversion, an integrated process with the combinatorial pretreatments of steam explosion and other pretreatments as the core should be feasible and conform to the plant biomass refinery concept. Combinatorial pretreatments of steam explosion and other pretreatments should be further exploited based on the type and intrinsic characteristics of the plant biomass used, the bio-based products to be made, and the complementarity of the processes. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A combinatorial enumeration problem of RNA secondary structures

African Journals Online (AJOL)

use

2011-12-21

Dec 21, 2011 ... interesting combinatorial questions (Chen et al., 2005;. Liu, 2006; Schmitt and Waterman 1994; Stein and. Waterman 1978). The research on the enumeration of. RNA secondary structures becomes one of the hot topics in Computational Molecular Biology. An RNA molecule is described by its sequences of.

Graphical-based construction of combinatorial geometries for radiation transport and shielding applications

International Nuclear Information System (INIS)

Burns, T.J.

1992-01-01

A graphical-based code system is being developed at ORNL to manipulate combinatorial geometries for radiation transport and shielding applications. The current version (basically a combinatorial geometry debugger) consists of two parts: a FORTRAN-based ''view'' generator and a Microsoft Windows application for displaying the geometry. Options and features of both modules are discussed. Examples illustrating the various options available are presented. The potential for utilizing the images produced using the debugger as a visualization tool for the output of the radiation transport codes is discussed as is the future direction of the development

Solutions manual to accompany Combinatorial reasoning an introduction to the art of counting

CERN Document Server

DeTemple, Duane

2014-01-01

This is a solutions manual to accompany Combinatorial Reasoning: An Introduction to the Art of CountingWritten by well-known scholars in the field, Combinatorial Reasoning: An Introduction to the Art of Counting introduces combinatorics alongside modern techniques, showcases the interdisciplinary aspects of the topic, and illustrates how to problem solve with a multitude of exercises throughout. The authors'' approach is very reader-friendly and avoids the ""scholarly tone"" found in many books on this topic.  

Olefin Metathesis in Peptidomimetics, Dynamic Combinatorial Chemistry, and Molecular Imprinting

National Research Council Canada - National Science Library

Low, Tammy K

2006-01-01

.... Our research goals consisted of employing olefin metathesis in the synthesis of peptidomimetics, and studying the feasibility of this method in dynamic combinatorial chemistry and molecular imprinting of nerve agents...

CUNY Graduate Center Workshops on Combinatorial and Additive Number Theory

CERN Document Server

2017-01-01

Based on talks from the 2015 and 2016 Combinatorial and Additive Number Theory (CANT) workshops at the City University of New York, these proceedings offer 19 peer-reviewed and edited papers on current topics in number theory. Held every year since 2003, the workshop series surveys state-of-the-art open problems in combinatorial and additive number theory and related parts of mathematics. Sumsets, partitions, convex polytopes and discrete geometry, Ramsey theory, primality testing, and cryptography are among the topics featured in this volume. Each contribution is dedicated to a specific topic that reflects the latest results by experts in the field. Researchers and graduate students interested in the current progress in number theory will find this selection of articles relevant and compelling. .

Sentence processing in an artificial language: Learning and using combinatorial constraints.

Science.gov (United States)

Amato, Michael S; MacDonald, Maryellen C

2010-07-01

A study combining artificial grammar and sentence comprehension methods investigated the learning and online use of probabilistic, nonadjacent combinatorial constraints. Participants learned a small artificial language describing cartoon monsters acting on objects. Self-paced reading of sentences in the artificial language revealed comprehenders' sensitivity to nonadjacent combinatorial constraints, without explicit awareness of the probabilities embedded in the language. These results show that even newly-learned constraints have an identifiable effect on online sentence processing. The rapidity of learning in this paradigm relative to others has implications for theories of implicit learning and its role in language acquisition. 2010 Elsevier B.V. All rights reserved.

Combinatorial Testing for VDM

DEFF Research Database (Denmark)

Larsen, Peter Gorm; Lausdahl, Kenneth; Battle, Nick

2010-01-01

by forgotten preconditions as well as broken invariants and post-conditions. Trace definitions are defined as regular expressions describing possible sequences of operation calls, and are conceptually similar to UML sequence diagrams. In this paper we present a tool enabling test automation based on VDM traces......Abstract—Combinatorial testing in VDM involves the automatic generation and execution of a large collection of test cases derived from templates provided in the form of trace definitions added to a VDM specification. The main value of this is the rapid detection of run-time errors caused......, and explain how it is possible to reduce large collections of test cases in different ways. Its use is illustrated with a small case study....

Quantum particle swarm approaches applied to combinatorial problems

Energy Technology Data Exchange (ETDEWEB)

Nicolau, Andressa dos S.; Schirru, Roberto; Lima, Alan M.M. de, E-mail: andressa@lmp.ufrj.br [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Programa de Engenharia Nuclear

2017-07-01

Quantum Particle Swarm Optimization (QPSO) is a global convergence algorithm that combines the classical PSO philosophy and quantum mechanics to improve performance of PSO. Different from PSO it only has the 'measurement' of the position equation for all particles. The process of 'measurement' in quantum mechanics, obey classic laws while the particle itself follows the quantum rules. QPSO works like PSO in search ability but has fewer parameters control. In order to improve the QPSO performance, some strategies have been proposed in the literature. Weighted QPSO (WQPSO) is a version of QPSO, where weight parameter is insert in the calculation of the balance between the global and local searching of the algorithm. It has been shown to perform well in finding the optimal solutions for many optimization problems. In this article random confinement was introduced in WQPSO. The WQPSO with random confinement was tested in two combinatorial problems. First, we execute the model on Travelling Salesman Problem (TSP) to find the parameters' values resulting in good solutions in general. Finally, the model was tested on Nuclear Reactor Reload Problem, and the performance was compared with QPSO standard. (author)

Quantum particle swarm approaches applied to combinatorial problems

International Nuclear Information System (INIS)

Nicolau, Andressa dos S.; Schirru, Roberto; Lima, Alan M.M. de

2017-01-01

Quantum Particle Swarm Optimization (QPSO) is a global convergence algorithm that combines the classical PSO philosophy and quantum mechanics to improve performance of PSO. Different from PSO it only has the 'measurement' of the position equation for all particles. The process of 'measurement' in quantum mechanics, obey classic laws while the particle itself follows the quantum rules. QPSO works like PSO in search ability but has fewer parameters control. In order to improve the QPSO performance, some strategies have been proposed in the literature. Weighted QPSO (WQPSO) is a version of QPSO, where weight parameter is insert in the calculation of the balance between the global and local searching of the algorithm. It has been shown to perform well in finding the optimal solutions for many optimization problems. In this article random confinement was introduced in WQPSO. The WQPSO with random confinement was tested in two combinatorial problems. First, we execute the model on Travelling Salesman Problem (TSP) to find the parameters' values resulting in good solutions in general. Finally, the model was tested on Nuclear Reactor Reload Problem, and the performance was compared with QPSO standard. (author)

A combinatorial approximation algorithm for CDMA downlink rate allocation

NARCIS (Netherlands)

Boucherie, Richardus J.; Bumb, A.F.; Endrayanto, A.I.; Woeginger, Gerhard; Raghavan, S.; Anandalingam, G.

2006-01-01

This paper presents a combinatorial algorithm for downlink rate allocation in Code Division Multiple Access (CDMA) mobile networks. By discretizing the coverage area into small segments, the transmit power requirements are characterized via a matrix representation that separates user and system

A combinatorial approximation algorithm for CDMA downlink rate allocation

NARCIS (Netherlands)

Boucherie, Richardus J.; Bumb, A.F.; Endrayanto, A.I.; Woeginger, Gerhard

2004-01-01

This paper presents a combinatorial algorithm for downlink rate allocation in Code Division Multiple Access (CDMA) mobile networks. By discretizing the coverage area into small segments, the transmit power requirements are characterized via a matrix representation that separates user and system

Development of tight-binding, chemical-reaction-dynamics simulator for combinatorial computational chemistry

International Nuclear Information System (INIS)

Kubo, Momoji; Ando, Minako; Sakahara, Satoshi; Jung, Changho; Seki, Kotaro; Kusagaya, Tomonori; Endou, Akira; Takami, Seiichi; Imamura, Akira; Miyamoto, Akira

2004-01-01

Recently, we have proposed a new concept called 'combinatorial computational chemistry' to realize a theoretical, high-throughput screening of catalysts and materials. We have already applied our combinatorial, computational-chemistry approach, mainly based on static first-principles calculations, to various catalysts and materials systems and its applicability to the catalysts and materials design was strongly confirmed. In order to realize more effective and efficient combinatorial, computational-chemistry screening, a high-speed, chemical-reaction-dynamics simulator based on quantum-chemical, molecular-dynamics method is essential. However, to the best of our knowledge, there is no chemical-reaction-dynamics simulator, which has an enough high-speed ability to perform a high-throughput screening. In the present study, we have succeeded in the development of a chemical-reaction-dynamics simulator based on our original, tight-binding, quantum-chemical, molecular-dynamics method, which is more than 5000 times faster than the regular first-principles, molecular-dynamics method. Moreover, its applicability and effectiveness to the atomistic clarification of the methanol-synthesis dynamics at reaction temperature were demonstrated

Biogeography-based combinatorial strategy for efficient autonomous underwater vehicle motion planning and task-time management

Science.gov (United States)

Zadeh, S. M.; Powers, D. M. W.; Sammut, K.; Yazdani, A. M.

2016-12-01

Autonomous Underwater Vehicles (AUVs) are capable of spending long periods of time for carrying out various underwater missions and marine tasks. In this paper, a novel conflict-free motion planning framework is introduced to enhance underwater vehicle's mission performance by completing maximum number of highest priority tasks in a limited time through a large scale waypoint cluttered operating field, and ensuring safe deployment during the mission. The proposed combinatorial route-path planner model takes the advantages of the Biogeography-Based Optimization (BBO) algorithm toward satisfying objectives of both higher-lower level motion planners and guarantees maximization of the mission productivity for a single vehicle operation. The performance of the model is investigated under different scenarios including the particular cost constraints in time-varying operating fields. To show the reliability of the proposed model, performance of each motion planner assessed separately and then statistical analysis is undertaken to evaluate the total performance of the entire model. The simulation results indicate the stability of the contributed model and its feasible application for real experiments.

Distributing the computation in combinatorial optimization experiments over the cloud

Directory of Open Access Journals (Sweden)

Mario Brcic

2017-12-01

Full Text Available Combinatorial optimization is an area of great importance since many of the real-world problems have discrete parameters which are part of the objective function to be optimized. Development of combinatorial optimization algorithms is guided by the empirical study of the candidate ideas and their performance over a wide range of settings or scenarios to infer general conclusions. Number of scenarios can be overwhelming, especially when modeling uncertainty in some of the problem’s parameters. Since the process is also iterative and many ideas and hypotheses may be tested, execution time of each experiment has an important role in the efficiency and successfulness. Structure of such experiments allows for significant execution time improvement by distributing the computation. We focus on the cloud computing as a cost-efficient solution in these circumstances. In this paper we present a system for validating and comparing stochastic combinatorial optimization algorithms. The system also deals with selection of the optimal settings for computational nodes and number of nodes in terms of performance-cost tradeoff. We present applications of the system on a new class of project scheduling problem. We show that we can optimize the selection over cloud service providers as one of the settings and, according to the model, it resulted in a substantial cost-savings while meeting the deadline.

Pydna: a simulation and documentation tool for DNA assembly strategies using python.

Science.gov (United States)

Pereira, Filipa; Azevedo, Flávio; Carvalho, Ângela; Ribeiro, Gabriela F; Budde, Mark W; Johansson, Björn

2015-05-02

Recent advances in synthetic biology have provided tools to efficiently construct complex DNA molecules which are an important part of many molecular biology and biotechnology projects. The planning of such constructs has traditionally been done manually using a DNA sequence editor which becomes error-prone as scale and complexity of the construction increase. A human-readable formal description of cloning and assembly strategies, which also allows for automatic computer simulation and verification, would therefore be a valuable tool. We have developed pydna, an extensible, free and open source Python library for simulating basic molecular biology DNA unit operations such as restriction digestion, ligation, PCR, primer design, Gibson assembly and homologous recombination. A cloning strategy expressed as a pydna script provides a description that is complete, unambiguous and stable. Execution of the script automatically yields the sequence of the final molecule(s) and that of any intermediate constructs. Pydna has been designed to be understandable for biologists with limited programming skills by providing interfaces that are semantically similar to the description of molecular biology unit operations found in literature. Pydna simplifies both the planning and sharing of cloning strategies and is especially useful for complex or combinatorial DNA molecule construction. An important difference compared to existing tools with similar goals is the use of Python instead of a specifically constructed language, providing a simulation environment that is more flexible and extensible by the user.

Some Combinatorial Interpretations and Applications of Fuss-Catalan Numbers

OpenAIRE

Lin, Chin-Hung

2011-01-01

Fuss-Catalan number is a family of generalized Catalan numbers. We begin by two definitions of Fuss-Catalan numbers and some basic properties. And we give some combinatorial interpretations different from original Catalan numbers. Finally we generalize the Jonah's theorem as its applications.

Construction of a virtual combinatorial library using SMILES strings to discover potential structure-diverse PPAR modulators.

Science.gov (United States)

Liao, Chenzhong; Liu, Bing; Shi, Leming; Zhou, Jiaju; Lu, Xian-Ping

2005-07-01

Based on the structural characters of PPAR modulators, a virtual combinatorial library containing 1226,625 compounds was constructed using SMILES strings. Selected ADME filters were employed to compel compounds having poor drug-like properties from this library. This library was converted to sdf and mol2 files by CONCORD 4.0, and was then docked to PPARgamma by DOCK 4.0 to identify new chemical entities that may be potential drug leads against type 2 diabetes and other metabolic diseases. The method to construct virtual combinatorial library using SMILES strings was further visualized by Visual Basic.net that can facilitate the needs of generating other type virtual combinatorial libraries.

Random Combinatorial Gradient Metasurface for Broadband, Wide-Angle and Polarization-Independent Diffusion Scattering.

Science.gov (United States)

Zhuang, Yaqiang; Wang, Guangming; Liang, Jiangang; Cai, Tong; Tang, Xiao-Lan; Guo, Tongfeng; Zhang, Qingfeng

2017-11-29

This paper proposes an easy, efficient strategy for designing broadband, wide-angle and polarization-independent diffusion metasurface for radar cross section (RCS) reduction. A dual-resonance unit cell, composed of a cross wire and cross loop (CWCL), is employed to enhance the phase bandwidth covering the 2π range. Both oblique-gradient and horizontal-gradient phase supercells are designed for illustration. The numerical results agree well with the theoretical ones. To significantly reduce backward scattering, the random combinatorial gradient metasurface (RCGM) is subsequently constructed by collecting eight supercells with randomly distributed gradient directions. The proposed metasurface features an enhanced specular RCS reduction performance and less design complexity compared to other candidates. Both simulated and measured results show that the proposed RCGM can significantly suppress RCS and exhibits broadband, wide-angle and polarization independence features.

Combinatorial Libraries As a Tool for the Discovery of Novel, Broad-Spectrum Antibacterial Agents Targeting the ESKAPE Pathogens.

Science.gov (United States)

Fleeman, Renee; LaVoi, Travis M; Santos, Radleigh G; Morales, Angela; Nefzi, Adel; Welmaker, Gregory S; Medina-Franco, José L; Giulianotti, Marc A; Houghten, Richard A; Shaw, Lindsey N

2015-04-23

Mixture based synthetic combinatorial libraries offer a tremendous enhancement for the rate of drug discovery, allowing the activity of millions of compounds to be assessed through the testing of exponentially fewer samples. In this study, we used a scaffold-ranking library to screen 37 different libraries for antibacterial activity against the ESKAPE pathogens. Each library contained between 10000 and 750000 structural analogues for a total of >6 million compounds. From this, we identified a bis-cyclic guanidine library that displayed strong antibacterial activity. A positional scanning library for these compounds was developed and used to identify the most effective functional groups at each variant position. Individual compounds were synthesized that were broadly active against all ESKAPE organisms at concentrations development of resistance, and displayed almost no toxicity when tested against human lung cells and erythrocytes. Using a murine model of peritonitis, we also demonstrate that these agents are highly efficacious in vivo.

An Atlas of Combinatorial Transcriptional Regulation in Mouse and Man

KAUST Repository

Ravasi, Timothy; Suzuki, Harukazu; Cannistraci, Carlo; Katayama, Shintaro; Bajic, Vladimir B.; Tan, Kai; Akalin, Altuna; Schmeier, Sebastian; Kanamori-Katayama, Mutsumi; Bertin, Nicolas; Carninci, Piero; Daub, Carsten O.; Forrest, Alistair R.R.; Gough, Julian; Grimmond, Sean; Han, Jung-Hoon; Hashimoto, Takehiro; Hide, Winston; Hofmann, Oliver; Kamburov, Atanas; Kaur, Mandeep; Kawaji, Hideya; Kubosaki, Atsutaka; Lassmann, Timo; van Nimwegen, Erik; MacPherson, Cameron Ross; Ogawa, Chihiro; Radovanovic, Aleksandar; Schwartz, Ariel; Teasdale, Rohan D.; Tegné r, Jesper; Lenhard, Boris; Teichmann, Sarah A.; Arakawa, Takahiro; Ninomiya, Noriko; Murakami, Kayoko; Tagami, Michihira; Fukuda, Shiro; Imamura, Kengo; Kai, Chikatoshi; Ishihara, Ryoko; Kitazume, Yayoi; Kawai, Jun; Hume, David A.; Ideker, Trey; Hayashizaki, Yoshihide

2010-01-01

Combinatorial interactions among transcription factors are critical to directing tissue-specific gene expression. To build a global atlas of these combinations, we have screened for physical interactions among the majority of human and mouse DNA-binding transcription factors (TFs). The complete networks contain 762 human and 877 mouse interactions. Analysis of the networks reveals that highly connected TFs are broadly expressed across tissues, and that roughly half of the measured interactions are conserved between mouse and human. The data highlight the importance of TF combinations for determining cell fate, and they lead to the identification of a SMAD3/FLI1 complex expressed during development of immunity. The availability of large TF combinatorial networks in both human and mouse will provide many opportunities to study gene regulation, tissue differentiation, and mammalian evolution.

An Atlas of Combinatorial Transcriptional Regulation in Mouse and Man

KAUST Repository

Ravasi, Timothy

2010-03-01

Combinatorial interactions among transcription factors are critical to directing tissue-specific gene expression. To build a global atlas of these combinations, we have screened for physical interactions among the majority of human and mouse DNA-binding transcription factors (TFs). The complete networks contain 762 human and 877 mouse interactions. Analysis of the networks reveals that highly connected TFs are broadly expressed across tissues, and that roughly half of the measured interactions are conserved between mouse and human. The data highlight the importance of TF combinations for determining cell fate, and they lead to the identification of a SMAD3/FLI1 complex expressed during development of immunity. The availability of large TF combinatorial networks in both human and mouse will provide many opportunities to study gene regulation, tissue differentiation, and mammalian evolution.

Skeletal Diversity in Combinatorial Fashion: A New Format for the Castagnoli-Cushman Reaction.

Science.gov (United States)

Lepikhina, Anastasia; Dar'in, Dmitry; Bakulina, Olga; Chupakhin, Evgeny; Krasavin, Mikhail

2017-11-13

A new format for the Castagnoli-Cushman reaction of structurally diverse dicarboxylic acids, amines, and aldehydes in the presence of acetic anhydride as dehydrating agent is described. The reaction is distinctly amenable to parallel format: the combinatorial array of 180 reactions delivered 157 products of >85% purity without chromatographic purification (of this number, 143 compounds had >94% purity). The new method offers a convenient preparation of the skeletally and peripherally diverse, lead- and druglike γ- and δ-lactam carboxylic acids with high diastereoselectivity in combinatorial fashion.

Phase Transitions in Combinatorial Optimization Problems: Basics, Algorithms and Statistical Mechanics

Science.gov (United States)

Hartmann, Alexander K.; Weigt, Martin

2005-10-01

A concise, comprehensive introduction to the topic of statistical physics of combinatorial optimization, bringing together theoretical concepts and algorithms from computer science with analytical methods from physics. The result bridges the gap between statistical physics and combinatorial optimization, investigating problems taken from theoretical computing, such as the vertex-cover problem, with the concepts and methods of theoretical physics. The authors cover rapid developments and analytical methods that are both extremely complex and spread by word-of-mouth, providing all the necessary basics in required detail. Throughout, the algorithms are shown with examples and calculations, while the proofs are given in a way suitable for graduate students, post-docs, and researchers. Ideal for newcomers to this young, multidisciplinary field.

Development of automatic combinatorial system for synthesis of nanoparticles using microreactors

Energy Technology Data Exchange (ETDEWEB)

Watanabe, Kosuke; Maeda, Hideaki [Interdisciplinary Graduate School of Engineering Sciences, Kyushu University, 6-1 Kasuga-koen, Kasuga, Fukuoka, 816-8580 (Japan); Orimoto, Yuuichi; Yamashita, Kenichi; Uehara, Masato; Nakamura, Hiroyuki [Measurement Solution Research Center, National Institute of Advanced Industrial Science and Technology (AIST), 807-1, Shuku, Tosu, Saga, 841-0052 (Japan); Furuya, Takeshi, E-mail: maeda-h@aist.go.jp [Nanosystem Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, 305-8565 (Japan)

2011-10-29

In this study, automatic system for combinatorial synthesis of nanoparticles (NPs) was developed and optimization of reaction parameter for NPs synthesis was performed. Microreactor was employed for kinetic control constantly. Programmable equipments were employed for additional speed up and used a microreactor. Six reaction condition parameters were systematically combined to produce CdSe synthesis condition sets. Reaction conditions of 3404 experimental sets were synthesized and characterized in 1 month. As a result of some multivariate analyses using the numerous and complicated data, we found as follows: 1) neural network is an effective method to analyze data from combinatorial synthesis, 2) weighting evaluation method was effective to find the condition for balanced NP properties.

Combinatorial algorithms enabling computational science: tales from the front

International Nuclear Information System (INIS)

Bhowmick, Sanjukta; Boman, Erik G; Devine, Karen; Gebremedhin, Assefaw; Hendrickson, Bruce; Hovland, Paul; Munson, Todd; Pothen, Alex

2006-01-01

Combinatorial algorithms have long played a crucial enabling role in scientific and engineering computations. The importance of discrete algorithms continues to grow with the demands of new applications and advanced architectures. This paper surveys some recent developments in this rapidly changing and highly interdisciplinary field

Combinatorial algorithms enabling computational science: tales from the front

Energy Technology Data Exchange (ETDEWEB)

Bhowmick, Sanjukta [Mathematics and Computer Science Division, Argonne National Laboratory (United States); Boman, Erik G [Discrete Algorithms and Math Department, Sandia National Laboratories (United States); Devine, Karen [Discrete Algorithms and Math Department, Sandia National Laboratories (United States); Gebremedhin, Assefaw [Computer Science Department, Old Dominion University (United States); Hendrickson, Bruce [Discrete Algorithms and Math Department, Sandia National Laboratories (United States); Hovland, Paul [Mathematics and Computer Science Division, Argonne National Laboratory (United States); Munson, Todd [Mathematics and Computer Science Division, Argonne National Laboratory (United States); Pothen, Alex [Computer Science Department, Old Dominion University (United States)

2006-09-15

Combinatorial algorithms have long played a crucial enabling role in scientific and engineering computations. The importance of discrete algorithms continues to grow with the demands of new applications and advanced architectures. This paper surveys some recent developments in this rapidly changing and highly interdisciplinary field.

Dynamic combinatorial libraries based on hydrogen-bonde molecular boxes

NARCIS (Netherlands)

Kerckhoffs, J.M.C.A.; Mateos timoneda, Miguel; Reinhoudt, David; Crego Calama, Mercedes

2007-01-01

This article describes two different types of dynamic combinatorial libraries of host and guest molecules. The first part of this article describes the encapsulation of alizarin trimer 2 a3 by dynamic mixtures of up to twenty different self-assembled molecular receptors together with the

Development of Combinatorial Methods for Alloy Design and Optimization

International Nuclear Information System (INIS)

Pharr, George M.; George, Easo P.; Santella, Michael L

2005-01-01

The primary goal of this research was to develop a comprehensive methodology for designing and optimizing metallic alloys by combinatorial principles. Because conventional techniques for alloy preparation are unavoidably restrictive in the range of alloy composition that can be examined, combinatorial methods promise to significantly reduce the time, energy, and expense needed for alloy design. Combinatorial methods can be developed not only to optimize existing alloys, but to explore and develop new ones as well. The scientific approach involved fabricating an alloy specimen with a continuous distribution of binary and ternary alloy compositions across its surface--an ''alloy library''--and then using spatially resolved probing techniques to characterize its structure, composition, and relevant properties. The three specific objectives of the project were: (1) to devise means by which simple test specimens with a library of alloy compositions spanning the range interest can be produced; (2) to assess how well the properties of the combinatorial specimen reproduce those of the conventionally processed alloys; and (3) to devise screening tools which can be used to rapidly assess the important properties of the alloys. As proof of principle, the methodology was applied to the Fe-Ni-Cr ternary alloy system that constitutes many commercially important materials such as stainless steels and the H-series and C-series heat and corrosion resistant casting alloys. Three different techniques were developed for making alloy libraries: (1) vapor deposition of discrete thin films on an appropriate substrate and then alloying them together by solid-state diffusion; (2) co-deposition of the alloying elements from three separate magnetron sputtering sources onto an inert substrate; and (3) localized melting of thin films with a focused electron-beam welding system. Each of the techniques was found to have its own advantages and disadvantages. A new and very powerful technique for

Combinatorial analysis of enzymatic bottlenecks of L-tyrosine pathway by p-coumaric acid production in Saccharomyces cerevisiae.

Science.gov (United States)

Mao, Jiwei; Liu, Quanli; Song, Xiaofei; Wang, Hesuiyuan; Feng, Hui; Xu, Haijin; Qiao, Mingqiang

2017-07-01

To identify new enzymatic bottlenecks of L-tyrosine pathway for further improving the production of L-tyrosine and its derivatives. When ARO4 and ARO7 were deregulated by their feedback resistant derivatives in the host strains, the ARO2 and TYR1 genes, coding for chorismate synthase and prephenate dehydrogenase were further identified as new important rate-limiting steps. The yield of p-coumaric acid in the feedback-resistant strain overexpressing ARO2 or TYR1, was significantly increased from 6.4 to 16.2 and 15.3 mg l -1 , respectively. Subsequently, we improved the strain by combinatorial engineering of pathway genes increasing the yield of p-coumaric acid by 12.5-fold (from 1.7 to 21.3 mg l -1 ) compared with the wild-type strain. Batch cultivations revealed that p-coumaric acid production was correlated with cell growth, and the formation of by-product acetate of the best producer NK-M6 increased to 31.1 mM whereas only 19.1 mM acetate was accumulated by the wild-type strain. Combinatorial metabolic engineering provides a new strategy for further improvement of L-tyrosine or other metabolic biosynthesis pathways in S. cerevisiae.

Synthetic detergents: 100 years of history

Directory of Open Access Journals (Sweden)

Ana Carolina Kogawa

2017-09-01

Full Text Available In the year 2016 the synthetic detergents complete 100 years and in this story they evolved as cleaners. They are already part of the routine of thousands of people worldwide. For a higher power of cleaning of the detergent, today, are added phosphates, the main responsible for environmental problems. After 100 years of synthetic detergents, the effect of the combination of various cleaners on the environment is a gap. Legislation and guidelines about the other components of the formula of cleaners still missing. Even the term biodegradable can be best placed on the diversity of products currently entitled biodegradable. A lot attitudes can still be taken to continuously improve the relationship between the parties involved, animals, plants, waters and men, so that in another 100 years continues to exist this interaction with the environment without destroying it. The marketing used by synthetic detergent companies evolved a lot over the years and showed maturity to deal with changes in theories and strategies for promotion and even with the constant social reform that its consumer lived, accompanying them intelligently to be able to capture their changing needs and desires, and so assemble the best way to connect to them. This paper focuses on the subject synthetic detergents as well as (i types and applications, (ii threats, (iii sustainability, (iv legislation, (v packaging and (vi marketing strategies.

Synthetic detergents: 100 years of history.

Science.gov (United States)

Kogawa, Ana Carolina; Cernic, Beatriz Gamberini; do Couto, Leandro Giovanni Domingos; Salgado, Hérida Regina Nunes

2017-09-01

In the year 2016 the synthetic detergents complete 100 years and in this story they evolved as cleaners. They are already part of the routine of thousands of people worldwide. For a higher power of cleaning of the detergent, today, are added phosphates, the main responsible for environmental problems. After 100 years of synthetic detergents, the effect of the combination of various cleaners on the environment is a gap. Legislation and guidelines about the other components of the formula of cleaners still missing. Even the term biodegradable can be best placed on the diversity of products currently entitled biodegradable. A lot attitudes can still be taken to continuously improve the relationship between the parties involved, animals, plants, waters and men, so that in another 100 years continues to exist this interaction with the environment without destroying it. The marketing used by synthetic detergent companies evolved a lot over the years and showed maturity to deal with changes in theories and strategies for promotion and even with the constant social reform that its consumer lived, accompanying them intelligently to be able to capture their changing needs and desires, and so assemble the best way to connect to them. This paper focuses on the subject synthetic detergents as well as (i) types and applications, (ii) threats, (iii) sustainability, (iv) legislation, (v) packaging and (vi) marketing strategies.

Automatic generation of combinatorial test data

CERN Document Server

Zhang, Jian; Ma, Feifei

2014-01-01

This book reviews the state-of-the-art in combinatorial testing, with particular emphasis on the automatic generation of test data. It describes the most commonly used approaches in this area - including algebraic construction, greedy methods, evolutionary computation, constraint solving and optimization - and explains major algorithms with examples. In addition, the book lists a number of test generation tools, as well as benchmarks and applications. Addressing a multidisciplinary topic, it will be of particular interest to researchers and professionals in the areas of software testing, combi

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

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.

A combinatorial approach to diffeomorphism invariant quantum gauge theories

International Nuclear Information System (INIS)

Zapata, J.A.

1997-01-01

Quantum gauge theory in the connection representation uses functions of holonomies as configuration observables. Physical observables (gauge and diffeomorphism invariant) are represented in the Hilbert space of physical states; physical states are gauge and diffeomorphism invariant distributions on the space of functions of the holonomies of the edges of a certain family of graphs. Then a family of graphs embedded in the space manifold (satisfying certain properties) induces a representation of the algebra of physical observables. We construct a quantum model from the set of piecewise linear graphs on a piecewise linear manifold, and another manifestly combinatorial model from graphs defined on a sequence of increasingly refined simplicial complexes. Even though the two models are different at the kinematical level, they provide unitarily equivalent representations of the algebra of physical observables in separable Hilbert spaces of physical states (their s-knot basis is countable). Hence, the combinatorial framework is compatible with the usual interpretation of quantum field theory. copyright 1997 American Institute of Physics

Developing a synthetic national population to investigate the impact of different cardiovascular disease risk management strategies: A derivation and validation study.

Science.gov (United States)

Knight, Josh; Wells, Susan; Marshall, Roger; Exeter, Daniel; Jackson, Rod

2017-01-01

Many national cardiovascular disease (CVD) risk factor management guidelines now recommend that drug treatment decisions should be informed primarily by patients' multi-variable predicted risk of CVD, rather than on the basis of single risk factor thresholds. To investigate the potential impact of treatment guidelines based on CVD risk thresholds at a national level requires individual level data representing the multi-variable CVD risk factor profiles for a country's total adult population. As these data are seldom, if ever, available, we aimed to create a synthetic population, representing the joint CVD risk factor distributions of the adult New Zealand population. A synthetic population of 2,451,278 individuals, representing the actual age, gender, ethnicity and social deprivation composition of people aged 30-84 years who completed the 2013 New Zealand census was generated using Monte Carlo sampling. Each 'synthetic' person was then probabilistically assigned values of the remaining cardiovascular disease (CVD) risk factors required for predicting their CVD risk, based on data from the national census national hospitalisation and drug dispensing databases and a large regional cohort study, using Monte Carlo sampling and multiple imputation. Where possible, the synthetic population CVD risk distributions for each non-demographic risk factor were validated against independent New Zealand data sources. We were able to develop a synthetic national population with realistic multi-variable CVD risk characteristics. The construction of this population is the first step in the development of a micro-simulation model intended to investigate the likely impact of a range of national CVD risk management strategies that will inform CVD risk management guideline updates in New Zealand and elsewhere.

Gas-Foamed Scaffold Gradients for Combinatorial Screening in 3D

Directory of Open Access Journals (Sweden)

Joachim Kohn

2012-03-01

Full Text Available Current methods for screening cell-material interactions typically utilize a two-dimensional (2D culture format where cells are cultured on flat surfaces. However, there is a need for combinatorial and high-throughput screening methods to systematically screen cell-biomaterial interactions in three-dimensional (3D tissue scaffolds for tissue engineering. Previously, we developed a two-syringe pump approach for making 3D scaffold gradients for use in combinatorial screening of salt-leached scaffolds. Herein, we demonstrate that the two-syringe pump approach can also be used to create scaffold gradients using a gas-foaming approach. Macroporous foams prepared by a gas-foaming technique are commonly used for fabrication of tissue engineering scaffolds due to their high interconnectivity and good mechanical properties. Gas-foamed scaffold gradient libraries were fabricated from two biodegradable tyrosine-derived polycarbonates: poly(desaminotyrosyl-tyrosine ethyl ester carbonate (pDTEc and poly(desaminotyrosyl-tyrosine octyl ester carbonate (pDTOc. The composition of the libraries was assessed with Fourier transform infrared spectroscopy (FTIR and showed that pDTEc/pDTOc gas-foamed scaffold gradients could be repeatably fabricated. Scanning electron microscopy showed that scaffold morphology was similar between the pDTEc-rich ends and the pDTOc-rich ends of the gradient. These results introduce a method for fabricating gas-foamed polymer scaffold gradients that can be used for combinatorial screening of cell-material interactions in 3D.

Combinatorial nuclear level-density model

International Nuclear Information System (INIS)

Uhrenholt, H.; Åberg, S.; Dobrowolski, A.; Døssing, Th.; Ichikawa, T.; Möller, P.

2013-01-01

A microscopic nuclear level-density model is presented. The model is a completely combinatorial (micro-canonical) model based on the folded-Yukawa single-particle potential and includes explicit treatment of pairing, rotational and vibrational states. The microscopic character of all states enables extraction of level-distribution functions with respect to pairing gaps, parity and angular momentum. The results of the model are compared to available experimental data: level spacings at neutron separation energy, data on total level-density functions from the Oslo method, cumulative level densities from low-lying discrete states, and data on parity ratios. Spherical and deformed nuclei follow basically different coupling schemes, and we focus on deformed nuclei

Combinatorial optimization games

Energy Technology Data Exchange (ETDEWEB)

Deng, X. [York Univ., North York, Ontario (Canada); Ibaraki, Toshihide; Nagamochi, Hiroshi [Kyoto Univ. (Japan)

1997-06-01

We introduce a general integer programming formulation for a class of combinatorial optimization games, which immediately allows us to improve the algorithmic result for finding amputations in the core (an important solution concept in cooperative game theory) of the network flow game on simple networks by Kalai and Zemel. An interesting result is a general theorem that the core for this class of games is nonempty if and only if a related linear program has an integer optimal solution. We study the properties for this mathematical condition to hold for several interesting problems, and apply them to resolve algorithmic and complexity issues for their cores along the line as put forward in: decide whether the core is empty; if the core is empty, find an imputation in the core; given an imputation x, test whether x is in the core. We also explore the properties of totally balanced games in this succinct formulation of cooperative games.

Combinatorial effects of arginine and fluoride on oral bacteria.

Science.gov (United States)

Zheng, X; Cheng, X; Wang, L; Qiu, W; Wang, S; Zhou, Y; Li, M; Li, Y; Cheng, L; Li, J; Zhou, X; Xu, X

2015-02-01

Dental caries is closely associated with the microbial disequilibrium between acidogenic/aciduric pathogens and alkali-generating commensal residents within the dental plaque. Fluoride is a widely used anticaries agent, which promotes tooth hard-tissue remineralization and suppresses bacterial activities. Recent clinical trials have shown that oral hygiene products containing both fluoride and arginine possess a greater anticaries effect compared with those containing fluoride alone, indicating synergy between fluoride and arginine in caries management. Here, we hypothesize that arginine may augment the ecological benefit of fluoride by enriching alkali-generating bacteria in the plaque biofilm and thus synergizes with fluoride in controlling dental caries. Specifically, we assessed the combinatory effects of NaF/arginine on planktonic and biofilm cultures of Streptococcus mutans, Streptococcus sanguinis, and Porphyromonas gingivalis with checkerboard microdilution assays. The optimal NaF/arginine combinations were selected, and their combinatory effects on microbial composition were further examined in single-, dual-, and 3-species biofilm using bacterial species-specific fluorescence in situ hybridization and quantitative polymerase chain reaction. We found that arginine synergized with fluoride in suppressing acidogenic S. mutans in both planktonic and biofilm cultures. In addition, the NaF/arginine combination synergistically reduced S. mutans but enriched S. sanguinis within the multispecies biofilms. More importantly, the optimal combination of NaF/arginine maintained a "streptococcal pressure" against the potential growth of oral anaerobe P. gingivalis within the alkalized biofilm. Taken together, we conclude that the combinatory application of fluoride and arginine has a potential synergistic effect in maintaining a healthy oral microbial equilibrium and thus represents a promising ecological approach to caries management. © International & American

Combinatorial programming of human neuronal progenitors using magnetically-guided stoichiometric mRNA delivery.

Science.gov (United States)

Azimi, Sayyed M; Sheridan, Steven D; Ghannad-Rezaie, Mostafa; Eimon, Peter M; Yanik, Mehmet Fatih

2018-05-01

Identification of optimal transcription-factor expression patterns to direct cellular differentiation along a desired pathway presents significant challenges. We demonstrate massively combinatorial screening of temporally-varying mRNA transcription factors to direct differentiation of neural progenitor cells using a dynamically-reconfigurable magnetically-guided spotting technology for localizing mRNA, enabling experiments on millimetre size spots. In addition, we present a time-interleaved delivery method that dramatically reduces fluctuations in the delivered transcription-factor copy-numbers per cell. We screened combinatorial and temporal delivery of a pool of midbrain-specific transcription factors to augment the generation of dopaminergic neurons. We show that the combinatorial delivery of LMX1A, FOXA2 and PITX3 is highly effective in generating dopaminergic neurons from midbrain progenitors. We show that LMX1A significantly increases TH -expression levels when delivered to neural progenitor cells either during proliferation or after induction of neural differentiation, while FOXA2 and PITX3 increase expression only when delivered prior to induction, demonstrating temporal dependence of factor addition. © 2018, Azimi et al.

Synthetic neurosteroids on brain protection

Directory of Open Access Journals (Sweden)

Mariana Rey

2015-01-01

Full Text Available Neurosteroids, like allopregnanolone and pregnanolone, are endogenous regulators of neuronal excitability. Inside the brain, they are highly selective and potent modulators of GABA A receptor activity. Their anticonvulsant, anesthetics and anxiolytic properties are useful for the treatments of several neurological and psychiatric disorders via reducing the risks of side effects obtained with the commercial drugs. The principal disadvantages of endogenous neurosteroids administration are their rapid metabolism and their low oral bioavailability. Synthetic steroids analogues with major stability or endogenous neurosteroids stimulation synthesis might constitute promising novel strategies for the treatment of several disorders. Numerous studies indicate that the 3α-hydroxyl configuration is the key for binding and activity, but modifications in the steroid nucleus may emphasize different pharmacophores. So far, several synthetic steroids have been developed with successful neurosteroid-like effects. In this work, we summarize the properties of various synthetic steroids probed in trials throughout the analysis of several neurosteroids-like actions.

Production of Fatty Acid-Derived Valuable Chemicals in Synthetic Microbes

International Nuclear Information System (INIS)

Yu, Ai-Qun; Pratomo Juwono, Nina Kurniasih; Leong, Susanna Su Jan; Chang, Matthew Wook

2014-01-01

Fatty acid derivatives, such as hydroxy fatty acids, fatty alcohols, fatty acid methyl/ethyl esters, and fatty alka(e)nes, have a wide range of industrial applications including plastics, lubricants, and fuels. Currently, these chemicals are obtained mainly through chemical synthesis, which is complex and costly, and their availability from natural biological sources is extremely limited. Metabolic engineering of microorganisms has provided a platform for effective production of these valuable biochemicals. Notably, synthetic biology-based metabolic engineering strategies have been extensively applied to refactor microorganisms for improved biochemical production. Here, we reviewed: (i) the current status of metabolic engineering of microbes that produce fatty acid-derived valuable chemicals, and (ii) the recent progress of synthetic biology approaches that assist metabolic engineering, such as mRNA secondary structure engineering, sensor-regulator system, regulatable expression system, ultrasensitive input/output control system, and computer science-based design of complex gene circuits. Furthermore, key challenges and strategies were discussed. Finally, we concluded that synthetic biology provides useful metabolic engineering strategies for economically viable production of fatty acid-derived valuable chemicals in engineered microbes.

Production of Fatty Acid-Derived Valuable Chemicals in Synthetic Microbes

Energy Technology Data Exchange (ETDEWEB)

Yu, Ai-Qun; Pratomo Juwono, Nina Kurniasih [Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore (Singapore); Synthetic Biology Research Program, National University of Singapore, Singapore (Singapore); Leong, Susanna Su Jan [Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore (Singapore); Synthetic Biology Research Program, National University of Singapore, Singapore (Singapore); Singapore Institute of Technology, Singapore (Singapore); Chang, Matthew Wook, E-mail: bchcmw@nus.edu.sg [Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore (Singapore); Synthetic Biology Research Program, National University of Singapore, Singapore (Singapore)

2014-12-23

Fatty acid derivatives, such as hydroxy fatty acids, fatty alcohols, fatty acid methyl/ethyl esters, and fatty alka(e)nes, have a wide range of industrial applications including plastics, lubricants, and fuels. Currently, these chemicals are obtained mainly through chemical synthesis, which is complex and costly, and their availability from natural biological sources is extremely limited. Metabolic engineering of microorganisms has provided a platform for effective production of these valuable biochemicals. Notably, synthetic biology-based metabolic engineering strategies have been extensively applied to refactor microorganisms for improved biochemical production. Here, we reviewed: (i) the current status of metabolic engineering of microbes that produce fatty acid-derived valuable chemicals, and (ii) the recent progress of synthetic biology approaches that assist metabolic engineering, such as mRNA secondary structure engineering, sensor-regulator system, regulatable expression system, ultrasensitive input/output control system, and computer science-based design of complex gene circuits. Furthermore, key challenges and strategies were discussed. Finally, we concluded that synthetic biology provides useful metabolic engineering strategies for economically viable production of fatty acid-derived valuable chemicals in engineered microbes.

Synthetic biology era: Improving antibiotic's world.

Science.gov (United States)

Guzmán-Trampe, Silvia; Ceapa, Corina D; Manzo-Ruiz, Monserrat; Sánchez, Sergio

2017-06-15

The emergence of antibiotic-resistant pathogen microorganisms is problematic in the context of the current spectrum of available medication. The poor specificity and the high toxicity of some available molecules have made imperative the search for new strategies to improve the specificity and to pursue the discovery of novel compounds with increased bioactivity. Using living cells as platforms, synthetic biology has counteracted this problem by offering novel pathways to create synthetic systems with improved and desired functions. Among many other biotechnological approaches, the advances in synthetic biology have made it possible to design and construct novel biological systems in order to look for new drugs with increased bioactivity. Advancements have also been made in the redesigning of RNA and DNA molecules in order to engineer antibiotic clusters for antibiotic overexpression. As for the production of these antibacterial compounds, yeasts and filamentous fungi as well as gene therapy are utilized to enhance protein solubility. Specific delivery is achieved by creating chimeras using plant genes into bacterial hosts. Some of these synthetic systems are currently in clinical trials, proving the proficiency of synthetic biology in terms of both pharmacological activities as well as an increase in the biosafety of treatments. It is possible that we may just be seeing the tip of the iceberg, and synthetic biology applications will overpass expectations beyond our present knowledge. Copyright © 2017. Published by Elsevier Inc.

Lexicographic goal programming and assessment tools for a combinatorial production problem.

Science.gov (United States)

2008-01-01

NP-complete combinatorial problems often necessitate the use of near-optimal solution techniques including : heuristics and metaheuristics. The addition of multiple optimization criteria can further complicate : comparison of these solution technique...

A Combinatory Approach for Selecting Prognostic Genes in Microarray Studies of Tumour Survivals

Directory of Open Access Journals (Sweden)

Qihua Tan

2009-01-01

Full Text Available Different from significant gene expression analysis which looks for genes that are differentially regulated, feature selection in the microarray-based prognostic gene expression analysis aims at finding a subset of marker genes that are not only differentially expressed but also informative for prediction. Unfortunately feature selection in literature of microarray study is predominated by the simple heuristic univariate gene filter paradigm that selects differentially expressed genes according to their statistical significances. We introduce a combinatory feature selection strategy that integrates differential gene expression analysis with the Gram-Schmidt process to identify prognostic genes that are both statistically significant and highly informative for predicting tumour survival outcomes. Empirical application to leukemia and ovarian cancer survival data through-within- and cross-study validations shows that the feature space can be largely reduced while achieving improved testing performances.

New high-throughput material-exploration system based on combinatorial chemistry and electrostatic atomization

International Nuclear Information System (INIS)

Fujimoto, K.; Takahashi, H.; Ito, S.; Inoue, S.; Watanabe, M.

2006-01-01

As a tool to facilitate future material explorations, our group has developed a new combinatorial system for the high-throughput preparation of compounds made up of more than three components. The system works in two steps: the atomization of a liquid by a high electric field followed by deposition to a grounded substrate. The combinatorial system based on this method has plural syringe pumps. The each starting materials are fed through the syringe pumps into a manifold, thoroughly mixed as they pass through the manifold, and atomized from the tip of a stainless steel nozzle onto a grounded substrate

"One-sample concept" micro-combinatory for high throughput TEM of binary films.

Science.gov (United States)

Sáfrán, György

2018-04-01

Phases of thin films may remarkably differ from that of bulk. Unlike to the comprehensive data files of Binary Phase Diagrams [1] available for bulk, complete phase maps for thin binary layers do not exist. This is due to both the diverse metastable, non-equilibrium or instable phases feasible in thin films and the required volume of characterization work with analytical techniques like TEM, SAED and EDS. The aim of the present work was to develop a method that remarkably facilitates the TEM study of the diverse binary phases of thin films, or the creation of phase maps. A micro-combinatorial method was worked out that enables both preparation and study of a gradient two-component film within a single TEM specimen. For a demonstration of the technique thin Mn x Al 1- x binary samples with evolving concentration from x = 0 to x = 1 have been prepared so that the transition from pure Mn to pure Al covers a 1.5 mm long track within the 3 mm diameter TEM grid. The proposed method enables the preparation and study of thin combinatorial samples including all feasible phases as a function of composition or other deposition parameters. Contrary to known "combinatorial chemistry", in which a series of different samples are deposited in one run, and investigated, one at a time, the present micro-combinatorial method produces a single specimen condensing a complete library of a binary system that can be studied, efficiently, within a single TEM session. That provides extremely high throughput for TEM characterization of composition-dependent phases, exploration of new materials, or the construction of phase diagrams of binary films. Copyright © 2018 Elsevier B.V. All rights reserved.

[Progress in synthetic biology of pinocembrin].

Science.gov (United States)

Guo, Lei; Kong, Jianqiang

2015-04-01

Pinocembrin, belonging to flavanons, was isolated from various plants. Pinocembrin has a variety of pharmacological activities, such as neuroprotective effect, antimicrobial activity, and antioxidant efficacy. Pinocembrin was approved as class I drugs to its phase II clinical trial by CFDA in 2009, mainly used for the treatment of ischemic stroke. As a promising compound, the manufacturing technologies of pinocembrin, including chemical synthesis, extraction from plant and synthetic biology, have attracted many attentions. Compared with the first two technologies, synthetic biology has many advantages, such as environment-friendly and low-cost. Construction of biosynthetic pathway in microorganism offers promising results for large scale pinocembrin production by fermentation after taking lots of effective strategies. This article reviews some of recent strategies in microorganisms to improve the yield, with focus on the selection of appropriate the key enzyme sources, the supply of precursors and cofactors by microorganisms, the choice of substance and the level of the key enzyme expression.

Synthetic biology platform technologies for antimicrobial applications.

Science.gov (United States)

Braff, Dana; Shis, David; Collins, James J

2016-10-01

The growing prevalence of antibiotic resistance calls for new approaches in the development of antimicrobial therapeutics. Likewise, improved diagnostic measures are essential in guiding the application of targeted therapies and preventing the evolution of therapeutic resistance. Discovery platforms are also needed to form new treatment strategies and identify novel antimicrobial agents. By applying engineering principles to molecular biology, synthetic biologists have developed platforms that improve upon, supplement, and will perhaps supplant traditional broad-spectrum antibiotics. Efforts in engineering bacteriophages and synthetic probiotics demonstrate targeted antimicrobial approaches that can be fine-tuned using synthetic biology-derived principles. Further, the development of paper-based, cell-free expression systems holds promise in promoting the clinical translation of molecular biology tools for diagnostic purposes. In this review, we highlight emerging synthetic biology platform technologies that are geared toward the generation of new antimicrobial therapies, diagnostics, and discovery channels. Copyright © 2016 Elsevier B.V. All rights reserved.

Modulating weak interactions for molecular recognition: a dynamic combinatorial analysis for assessing the contribution of electrostatics to the stability of CH-π bonds in water.

Science.gov (United States)

Jiménez-Moreno, Ester; Gómez, Ana M; Bastida, Agatha; Corzana, Francisco; Jiménez-Oses, Gonzalo; Jiménez-Barbero, Jesús; Asensio, Juan Luis

2015-03-27

Electrostatic and charge-transfer contributions to CH-π complexes can be modulated by attaching electron-withdrawing substituents to the carbon atom. While clearly stabilizing in the gas phase, the outcome of this chemical modification in water is more difficult to predict. Herein we provide a definitive and quantitative answer to this question employing a simple strategy based on dynamic combinatorial chemistry. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Strategies to distinguish new synthetic cannabinoid FUBIMINA (BIM-2201) intake from its isomer THJ-2201: metabolism of FUBIMINA in human hepatocytes

OpenAIRE

Diao, Xingxing; Scheidweiler, Karl B.; Wohlfarth, Ariane; Zhu, Mingshe; Pang, Shaokun; Huestis, Marilyn A.

2016-01-01

Since 2013, a new drugs-of-abuse trend attempts to bypass drug legislation by marketing isomers of scheduled synthetic cannabinoids (SCs), e.g., FUBIMINA (BIM-2201) and THJ-2201. It is much more challenging to confirm a specific isomer?s intake and distinguish it from its structural analog because the isomers and their major metabolites usually have identical molecular weights and display the same product ions. Here, we investigated isomers FUBIMINA and THJ-2201 and propose strategies to dist...

Dynamic Combinatorial Chemistry with Diselenides, Disulfides, Imines and Metal Coordination

DEFF Research Database (Denmark)

Sørensen, Anne

combinatorial chemistry, namely the reversible diselenide exchange reaction. The first part of the thesis describes the development of a thermally induced OAr → SeAr migration reaction. Here, it was proven possible to rearrange a variety of substituted O-aryl selenocarbamates into the corresponding Se...

Confluence of an extension of combinatory logic by Boolean constants

DEFF Research Database (Denmark)

Czajka, Łukasz

2017-01-01

We show confluence of a conditional term rewriting system CL-pc1, which is an extension of Combinatory Logic by Boolean constants. This solves problem 15 from the RTA list of open problems. The proof has been fully formalized in the Coq proof assistant....

Combinatorial chemistry approach to development of molecular plastic solar cells

NARCIS (Netherlands)

Godovsky, Dmitri; Inganäs, Olle; Brabec, Christoph J.; Sariciftci, N. Serdar; Hummelen, Jan C.; Janssen, Rene A.J.; Prato, M.; Maggini, M.; Segura, Jose; Martin, Nazario

1999-01-01

We used a combinatorial chemistry approach to develop the molecular plastic solar cells based on soluble fullerene derivatives or solubilized TCNQ molecules in combination with conjugated polymers. Profiles, formed by the diffusion of low molecular weight component in the spin-cast polymer host were

Comparison of combinatorial clustering methods on pharmacological data sets represented by machine learning-selected real molecular descriptors.

Science.gov (United States)

Rivera-Borroto, Oscar Miguel; Marrero-Ponce, Yovani; García-de la Vega, José Manuel; Grau-Ábalo, Ricardo del Corazón

2011-12-27

Cluster algorithms play an important role in diversity related tasks of modern chemoinformatics, with the widest applications being in pharmaceutical industry drug discovery programs. The performance of these grouping strategies depends on various factors such as molecular representation, mathematical method, algorithmical technique, and statistical distribution of data. For this reason, introduction and comparison of new methods are necessary in order to find the model that best fits the problem at hand. Earlier comparative studies report on Ward's algorithm using fingerprints for molecular description as generally superior in this field. However, problems still remain, i.e., other types of numerical descriptions have been little exploited, current descriptors selection strategy is trial and error-driven, and no previous comparative studies considering a broader domain of the combinatorial methods in grouping chemoinformatic data sets have been conducted. In this work, a comparison between combinatorial methods is performed,with five of them being novel in cheminformatics. The experiments are carried out using eight data sets that are well established and validated in the medical chemistry literature. Each drug data set was represented by real molecular descriptors selected by machine learning techniques, which are consistent with the neighborhood principle. Statistical analysis of the results demonstrates that pharmacological activities of the eight data sets can be modeled with a few of families with 2D and 3D molecular descriptors, avoiding classification problems associated with the presence of nonrelevant features. Three out of five of the proposed cluster algorithms show superior performance over most classical algorithms and are similar (or slightly superior in the most optimistic sense) to Ward's algorithm. The usefulness of these algorithms is also assessed in a comparative experiment to potent QSAR and machine learning classifiers, where they perform

Synthetic biology: Novel approaches for microbiology.

Science.gov (United States)

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

2015-06-01

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

Strategies for Efficient Charge Separation and Transfer in Artificial Photosynthesis of Solar Fuels.

Science.gov (United States)

Xu, Yuxing; Li, Ailong; Yao, Tingting; Ma, Changtong; Zhang, Xianwen; Shah, Jafar Hussain; Han, Hongxian

2017-11-23

Converting sunlight to solar fuels by artificial photosynthesis is an innovative science and technology for renewable energy. Light harvesting, photogenerated charge separation and transfer (CST), and catalytic reactions are the three primary steps in the processes involved in the conversion of solar energy to chemical energy (SE-CE). Among the processes, CST is the key "energy pump and delivery" step in determining the overall solar-energy conversion efficiency. Efficient CST is always high priority in designing and assembling artificial photosynthesis systems for solar-fuel production. This Review not only introduces the fundamental strategies for CST but also the combinatory application of these strategies to five types of the most-investigated semiconductor-based artificial photosynthesis systems: particulate, Z-scheme, hybrid, photoelectrochemical, and photovoltaics-assisted systems. We show that artificial photosynthesis systems with high SE-CE efficiency can be rationally designed and constructed through combinatory application of these strategies, setting a promising blueprint for the future of solar fuels. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Anti-termite efficacy of Capparis decidua and its combinatorial ...

African Journals Online (AJOL)

Michael Horsfall

ABSTRACT: Capparis deciduas and its combinatorial mixtures were evaluated to observe the anti-termite efficacy against Indian white termite Odontotermes obesus. These have shown very high termiticidal activity and wood protection in the soil. It is proved by very low LD50 values i.e. 0.0218mg/g and 0.021mg/g obtained ...

Combinatorial drug screening identifies Ewing sarcoma-specific sensitivities

OpenAIRE

Radic-Sarikas, Branka; Tsafou, Kalliopi P.; Emdal, Kristina B.; Papamarkou, Theodore; Huber, Kilian V.M.; Mutz, Cornelia; Toretsky, Jeffrey A.; Bennett, Keiryn L.; Olsen, Jesper V.; Brunak, Søren; Kovar, Heinrich; Superti-Furga, Giulio

2017-01-01

Improvements in survival for Ewing sarcoma pediatric and adolescent patients have been modest over the past 20 years. Combinations of anticancer agents endure as an option to overcome resistance to single treatments caused by compensatory pathways. Moreover, combinations are thought to lessen any associated adverse side effects through reduced dosing, which is particularly important in childhood tumors. Using a parallel phenotypic combinatorial screening approach of cells derived from three p...

ON range searching in the group model and combinatorial discrepancy

DEFF Research Database (Denmark)

Larsen, Kasper Green

2014-01-01

In this paper we establish an intimate connection between dynamic range searching in the group model and combinatorial discrepancy. Our result states that, for a broad class of range searching data structures (including all known upper bounds), it must hold that $t_u t_q=\\Omega(\\mbox{disc}^2......)$, where $t_u$ is the worst case update time, $t_q$ is the worst case query time, and disc is the combinatorial discrepancy of the range searching problem in question. This relation immediately implies a whole range of exceptionally high and near-tight lower bounds for all of the basic range searching...... problems. We list a few of them in the following: (1) For $d$-dimensional halfspace range searching, we get a lower bound of $t_u t_q=\\Omega(n^{1-1/d})$. This comes within an lg lg $n$ factor of the best known upper bound. (2) For orthogonal range searching, we get a lower bound of $t_u t...

Solidified self-nanoemulsifying formulation for oral delivery of combinatorial therapeutic regimen

DEFF Research Database (Denmark)

Jain, Amit K; Thanki, Kaushik; Jain, Sanyog

2014-01-01

PURPOSE: The present work reports rationalized development and characterization of solidified self-nanoemulsifying drug delivery system for oral delivery of combinatorial (tamoxifen and quercetin) therapeutic regimen. METHODS: Suitable oil for the preparation of liquid SNEDDS was selected based...

A Dynamic Combinatorial Approach for Identifying Side Groups that Stabilize DNA-Templated Supramolecular Self-Assemblies

Directory of Open Access Journals (Sweden)

Delphine Paolantoni

2015-02-01

Full Text Available DNA-templated self-assembly is an emerging strategy for generating functional supramolecular systems, which requires the identification of potent multi-point binding ligands. In this line, we recently showed that bis-functionalized guanidinium compounds can interact with ssDNA and generate a supramolecular complex through the recognition of the phosphodiester backbone of DNA. In order to probe the importance of secondary interactions and to identify side groups that stabilize these DNA-templated self-assemblies, we report herein the implementation of a dynamic combinatorial approach. We used an in situ fragment assembly process based on reductive amination and tested various side groups, including amino acids. The results reveal that aromatic and cationic side groups participate in secondary supramolecular interactions that stabilize the complexes formed with ssDNA.

Directed evolution combined with synthetic biology strategies expedite semi-rational engineering of genes and genomes.

Science.gov (United States)

Kang, Zhen; Zhang, Junli; Jin, Peng; Yang, Sen

2015-01-01

Owing to our limited understanding of the relationship between sequence and function and the interaction between intracellular pathways and regulatory systems, the rational design of enzyme-coding genes and de novo assembly of a brand-new artificial genome for a desired functionality or phenotype are difficult to achieve. As an alternative approach, directed evolution has been widely used to engineer genomes and enzyme-coding genes. In particular, significant developments toward DNA synthesis, DNA assembly (in vitro or in vivo), recombination-mediated genetic engineering, and high-throughput screening techniques in the field of synthetic biology have been matured and widely adopted, enabling rapid semi-rational genome engineering to generate variants with desired properties. In this commentary, these novel tools and their corresponding applications in the directed evolution of genomes and enzymes are discussed. Moreover, the strategies for genome engineering and rapid in vitro enzyme evolution are also proposed.

Synthetic bedding and wheeze in childhood.

Science.gov (United States)

Ponsonby, Anne-Louise; Dwyer, Terence; Kemp, Andrew; Cochrane, Jennifer; Couper, David; Carmichael, Allan

2003-01-01

The reasons for the increase in childhood asthma over time are unclear. The indoor environment is of particular concern. An adverse role for synthetic bedding on asthma development in childhood has been suggested by cross-sectional studies that have found an association between synthetic pillow use and childhood wheeze. Prospective data on infant bedding have not been available. Bedding data at 1 month of age were available from an infant survey for children who were participating in a 1995 follow-up study (N = 863; 78% traced). The 1995 follow-up was embedded in a larger cross-sectional survey involving 6,378 seven year olds in Tasmania (N = 92% of eligible). Outcome measures included respiratory symptoms as defined in the International Study of Asthma and Allergies in Childhood protocol. Frequent wheeze was defined as more than 12 wheeze episodes over the past year compared with no wheeze. Synthetic pillow use at 1 month of age was associated with frequent wheeze at age 7 (adjusted relative risk [aRR] = 2.5; 95% confidence interval [CI] = 1.2-5.5) independent of childhood exposure. Current synthetic pillow and quilt use was strongly associated with frequent wheeze (aRR = 5.2; CI = 1.3-20.6). Substantial trends were evident for an association of increasing number of synthetic bedding items with frequent wheeze and with increasing wheeze frequency. Among children with asthma, the age of onset of asthma occurred earlier if synthetic bedding was used in infancy. In this cohort, synthetic bedding was strongly and consistently associated with frequent childhood wheeze. The association did not appear to be attributable to bedding choice as part of an asthma management strategy.

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

KAUST Repository

Braguy, Justine; Zurbriggen, Matias D.

2016-01-01

of involved functional and regulatory mechanisms. The implementation of synthetic biology approaches is revolutionizing experimental biology in prokaryotes, yeasts and animal systems and can likewise contribute to a new era in plant biology. This review gives

Engineering novel synthetic strategy to develop mesocarbon microbeads for multi-functional applications

Science.gov (United States)

Chaudhary, Anisha; Teotia, Satish; Kumar, Rajeev; Ramesha, K.; Dhakate, Sanjay R.; Kumari, Saroj

2018-04-01

To assess the challenge of affordable technology, present synthetic strategies can be extended to new low-cost synthesis and processing methods that have potential to tailor the properties of the materials. Here we report, a novel method for the synthesis of mesocarbon microbeads (MCMB) through a pre-processing involved pyrolysis technique. The resulting MCMB is compressed into a product and effects of heat treatment temperature on different properties of MCMB is studied. The use of MCMB for the electromagnetic interference (EMI) shielding is new and hence, the effect of heat treatment temperature on EMI shielding effectiveness is studied in X-band. It is observed that EMI shielding effectiveness increases to ‑39.6 dB on increasing the heat treatment temperature. The high conductivity of MCMB plate heat treated upto 2500 °C contributes to highly conducting networks. Additionally, to investigate the electrochemical performance of MCMB as an anode material for lithium ion batteries, 2500 °C heat treated MCMB powder is used to fabricate the electrode. The MCMB electrode exhibits high discharge capacity of 345 mAh g‑1 with a stable capacity for over 50 cycles and good rate capability. Thus, MCMB synthesized by this novel approach can be used for the development of high performance anode materials for Li-ion batteries.

Introducing Dynamic Combinatorial Chemistry: Probing the Substrate Selectivity of Acetylcholinesterase

Science.gov (United States)

Angelin, Marcus; Larsson, Rikard; Vongvilai, Pornrapee; Ramstrom, Olof

2010-01-01

In this laboratory experiment, college students are introduced to dynamic combinatorial chemistry (DCC) and apply it to determine the substrate selectivity of acetylcholinesterase (AChE). Initially, the students construct a chemical library of dynamically interchanging thioesters and thiols. Then, AChE is added and allowed to select and hydrolyze…

WISB: Warwick Integrative Synthetic Biology Centre.

Science.gov (United States)

McCarthy, John

2016-06-15

Synthetic biology promises to create high-impact solutions to challenges in the areas of biotechnology, human/animal health, the environment, energy, materials and food security. Equally, synthetic biologists create tools and strategies that have the potential to help us answer important fundamental questions in biology. Warwick Integrative Synthetic Biology (WISB) pursues both of these mutually complementary 'build to apply' and 'build to understand' approaches. This is reflected in our research structure, in which a core theme on predictive biosystems engineering develops underpinning understanding as well as next-generation experimental/theoretical tools, and these are then incorporated into three applied themes in which we engineer biosynthetic pathways, microbial communities and microbial effector systems in plants. WISB takes a comprehensive approach to training, education and outreach. For example, WISB is a partner in the EPSRC/BBSRC-funded U.K. Doctoral Training Centre in synthetic biology, we have developed a new undergraduate module in the subject, and we have established five WISB Research Career Development Fellowships to support young group leaders. Research in Ethical, Legal and Societal Aspects (ELSA) of synthetic biology is embedded in our centre activities. WISB has been highly proactive in building an international research and training network that includes partners in Barcelona, Boston, Copenhagen, Madrid, Marburg, São Paulo, Tartu and Valencia. © 2016 The Author(s).

Phage Therapy in the Era of Synthetic Biology.

Science.gov (United States)

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

2016-10-03

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

First steps in combinatorial optimization on graphons: matchings

Czech Academy of Sciences Publication Activity Database

Doležal, Martin; Hladký, J.; Hu, P.; Piguet, Diana

2017-01-01

Roč. 61, August (2017), s. 359-365 ISSN 1571-0653 R&D Projects: GA ČR GA16-07378S; GA ČR GJ16-07822Y EU Projects: European Commission(XE) 628974 - PAECIDM Institutional support: RVO:67985840 ; RVO:67985807 Keywords : graphon * graph limits * matching * combinatorial optimization Subject RIV: BA - General Mathematics ; BA - General Mathematics (UIVT-O) OBOR OECD: Pure mathematics ; Pure mathematics (UIVT-O) http://www.sciencedirect.com/science/article/pii/S1571065317301452

First steps in combinatorial optimization on graphons: matchings

Czech Academy of Sciences Publication Activity Database

Doležal, Martin; Hladký, J.; Hu, P.; Piguet, Diana

2017-01-01

Roč. 61, August (2017), s. 359-365 ISSN 1571-0653 R&D Projects: GA ČR GA16-07378S; GA ČR GJ16-07822Y EU Projects: European Commission(XE) 628974 - PAECIDM Institutional support: RVO:67985840 ; RVO:67985807 Keywords : graphon * graph limits * matching * combinatorial optimization Subject RIV: BA - General Mathematics; BA - General Mathematics (UIVT-O) OBOR OECD: Pure mathematics; Pure mathematics (UIVT-O) http://www.sciencedirect.com/science/article/pii/S1571065317301452

Deciphering Cis-Regulatory Element Mediated Combinatorial Regulation in Rice under Blast Infected Condition.

Directory of Open Access Journals (Sweden)

Arindam Deb

Full Text Available Combinations of cis-regulatory elements (CREs present at the promoters facilitate the binding of several transcription factors (TFs, thereby altering the consequent gene expressions. Due to the eminent complexity of the regulatory mechanism, the combinatorics of CRE-mediated transcriptional regulation has been elusive. In this work, we have developed a new methodology that quantifies the co-occurrence tendencies of CREs present in a set of promoter sequences; these co-occurrence scores are filtered in three consecutive steps to test their statistical significance; and the significantly co-occurring CRE pairs are presented as networks. These networks of co-occurring CREs are further transformed to derive higher order of regulatory combinatorics. We have further applied this methodology on the differentially up-regulated gene-sets of rice tissues under fungal (Magnaporthe infected conditions to demonstrate how it helps to understand the CRE-mediated combinatorial gene regulation. Our analysis includes a wide spectrum of biologically important results. The CRE pairs having a strong tendency to co-occur often exhibit very similar joint distribution patterns at the promoters of rice. We couple the network approach with experimental results of plant gene regulation and defense mechanisms and find evidences of auto and cross regulation among TF families, cross-talk among multiple hormone signaling pathways, similarities and dissimilarities in regulatory combinatorics between different tissues, etc. Our analyses have pointed a highly distributed nature of the combinatorial gene regulation facilitating an efficient alteration in response to fungal attack. All together, our proposed methodology could be an important approach in understanding the combinatorial gene regulation. It can be further applied to unravel the tissue and/or condition specific combinatorial gene regulation in other eukaryotic systems with the availability of annotated genomic

Combinatorial Models for Assembly and Decomposition of Products

Directory of Open Access Journals (Sweden)

A. N. Bojko

2015-01-01

Full Text Available The paper discusses the most popular combinatorial models that are used for the synthesis of design solutions at the stage of the assembly process flow preparation. It shows that while assembling the product the relations of parts can be represented as a structure of preferences, which is formed on the basis of objective design restrictions put in at the stage of the product design. This structure is a binary preference relation pre-order. Its symmetrical part is equivalence and describes the entry of parts into the assembly unit. The asymmetric part is a partial order. It specifies part- ordering time in in the course of the assembly process. The structure of preferences is a minimal description of the restrictions and constraints in the assembly process. It can serve as a source for generating multiple assembly sequences of a product and its components, which are allowed by design. This multiplicity increases the likelihood of rational choice under uncertainty, unpredictable changes in the properties of technological or industrial systems.Incomplete dominance relation gives grounds for further examination and better understanding of the project situation. Operation field of the study is limited to a set of disparate elements of the partial order. Different strategies for processing the disparate elements may be offered, e.g. selection of the most informative pairs, comparison of which foremost linearizes the original partial order.

Dynamic combinatorial chemistry to identify binders of ThiT, an S-component of the energy-coupling factor transporter for thiamine

NARCIS (Netherlands)

Monjas, Leticia; Swier, Lotteke J Y M; Setyawati, Inda; Slotboom, Dirk Jan; Hirsch, Anna Katharina Herta

2017-01-01

We applied dynamic combinatorial chemistry (DCC) to identify ligands of ThiT, the S-component of the energy-coupling factor (ECF) transporter for thiamine in Lactococcus lactis. We used a pre-equilibrated dynamic combinatorial library (DCL) and saturation-transfer difference (STD) NMR spectroscopy

Dynamical System Approaches to Combinatorial Optimization

DEFF Research Database (Denmark)

Starke, Jens

2013-01-01

of large times as an asymptotically stable point of the dynamics. The obtained solutions are often not globally optimal but good approximations of it. Dynamical system and neural network approaches are appropriate methods for distributed and parallel processing. Because of the parallelization......Several dynamical system approaches to combinatorial optimization problems are described and compared. These include dynamical systems derived from penalty methods; the approach of Hopfield and Tank; self-organizing maps, that is, Kohonen networks; coupled selection equations; and hybrid methods...... thereof can be used as models for many industrial problems like manufacturing planning and optimization of flexible manufacturing systems. This is illustrated for an example in distributed robotic systems....

Method and apparatus for combinatorial chemistry

Science.gov (United States)

Foote, Robert S [Oak Ridge, TN

2012-06-05

A method and apparatus are provided for performing light-directed reactions in spatially addressable channels within a plurality of channels. One aspect of the invention employs photoactivatable reagents in solutions disposed into spatially addressable flow streams to control the parallel synthesis of molecules immobilized within the channels. The reagents may be photoactivated within a subset of channels at the site of immobilized substrate molecules or at a light-addressable site upstream from the substrate molecules. The method and apparatus of the invention find particularly utility in the synthesis of biopolymer arrays, e.g., oligonucleotides, peptides and carbohydrates, and in the combinatorial synthesis of small molecule arrays for drug discovery.

Slurry growth and gas retention in synthetic Hanford waste

International Nuclear Information System (INIS)

Bryan, S.A.; Pederson, L.R.; Scheele, R.D.

1992-09-01

This work seeks to establish chemical and physical processes responsible for the generation and retention of gases within waste from a particular high-level waste tank on the Hanford Site, Tank 101-SY, through the use of synthetic wastes on a laboratory scale. The goal of these activities is to support the development of mitigation/remediation strategies for Tank 101-SY. Laboratory studies of aged synthetic waste have shown that gas generation occurs thermally at a significant level at current tank temperatures. Gas compositions include the same gases produced in actual tank waste, primarily N 2 , N 2 O, and H 2 . Gas stoichiometries have been shown to be greatly influenced by several organic and inorganic constituents within the synthetic waste. Retention of gases in the synthetic waste is in the form of bubble attachment to solid particles

Geometric Generalisation of Surrogate Model-Based Optimisation to Combinatorial and Program Spaces

Directory of Open Access Journals (Sweden)

Yong-Hyuk Kim

2014-01-01

Full Text Available Surrogate models (SMs can profitably be employed, often in conjunction with evolutionary algorithms, in optimisation in which it is expensive to test candidate solutions. The spatial intuition behind SMs makes them naturally suited to continuous problems, and the only combinatorial problems that have been previously addressed are those with solutions that can be encoded as integer vectors. We show how radial basis functions can provide a generalised SM for combinatorial problems which have a geometric solution representation, through the conversion of that representation to a different metric space. This approach allows an SM to be cast in a natural way for the problem at hand, without ad hoc adaptation to a specific representation. We test this adaptation process on problems involving binary strings, permutations, and tree-based genetic programs.

Discovery of Cationic Polymers for Non-viral Gene Delivery using Combinatorial Approaches

Science.gov (United States)

Barua, Sutapa; Ramos, James; Potta, Thrimoorthy; Taylor, David; Huang, Huang-Chiao; Montanez, Gabriela; Rege, Kaushal

2015-01-01

Gene therapy is an attractive treatment option for diseases of genetic origin, including several cancers and cardiovascular diseases. While viruses are effective vectors for delivering exogenous genes to cells, concerns related to insertional mutagenesis, immunogenicity, lack of tropism, decay and high production costs necessitate the discovery of non-viral methods. Significant efforts have been focused on cationic polymers as non-viral alternatives for gene delivery. Recent studies have employed combinatorial syntheses and parallel screening methods for enhancing the efficacy of gene delivery, biocompatibility of the delivery vehicle, and overcoming cellular level barriers as they relate to polymer-mediated transgene uptake, transport, transcription, and expression. This review summarizes and discusses recent advances in combinatorial syntheses and parallel screening of cationic polymer libraries for the discovery of efficient and safe gene delivery systems. PMID:21843141

Integrative Analysis of Transcription Factor Combinatorial Interactions Using a Bayesian Tensor Factorization Approach

Science.gov (United States)

Ye, Yusen; Gao, Lin; Zhang, Shihua

2017-01-01

Transcription factors play a key role in transcriptional regulation of genes and determination of cellular identity through combinatorial interactions. However, current studies about combinatorial regulation is deficient due to lack of experimental data in the same cellular environment and extensive existence of data noise. Here, we adopt a Bayesian CANDECOMP/PARAFAC (CP) factorization approach (BCPF) to integrate multiple datasets in a network paradigm for determining precise TF interaction landscapes. In our first application, we apply BCPF to integrate three networks built based on diverse datasets of multiple cell lines from ENCODE respectively to predict a global and precise TF interaction network. This network gives 38 novel TF interactions with distinct biological functions. In our second application, we apply BCPF to seven types of cell type TF regulatory networks and predict seven cell lineage TF interaction networks, respectively. By further exploring the dynamics and modularity of them, we find cell lineage-specific hub TFs participate in cell type or lineage-specific regulation by interacting with non-specific TFs. Furthermore, we illustrate the biological function of hub TFs by taking those of cancer lineage and blood lineage as examples. Taken together, our integrative analysis can reveal more precise and extensive description about human TF combinatorial interactions. PMID:29033978

Machine learning meliorates computing and robustness in discrete combinatorial optimization problems.

Directory of Open Access Journals (Sweden)

Fushing Hsieh

2016-11-01

Full Text Available Discrete combinatorial optimization problems in real world are typically defined via an ensemble of potentially high dimensional measurements pertaining to all subjects of a system under study. We point out that such a data ensemble in fact embeds with system's information content that is not directly used in defining the combinatorial optimization problems. Can machine learning algorithms extract such information content and make combinatorial optimizing tasks more efficient? Would such algorithmic computations bring new perspectives into this classic topic of Applied Mathematics and Theoretical Computer Science? We show that answers to both questions are positive. One key reason is due to permutation invariance. That is, the data ensemble of subjects' measurement vectors is permutation invariant when it is represented through a subject-vs-measurement matrix. An unsupervised machine learning algorithm, called Data Mechanics (DM, is applied to find optimal permutations on row and column axes such that the permuted matrix reveals coupled deterministic and stochastic structures as the system's information content. The deterministic structures are shown to facilitate geometry-based divide-and-conquer scheme that helps optimizing task, while stochastic structures are used to generate an ensemble of mimicries retaining the deterministic structures, and then reveal the robustness pertaining to the original version of optimal solution. Two simulated systems, Assignment problem and Traveling Salesman problem, are considered. Beyond demonstrating computational advantages and intrinsic robustness in the two systems, we propose brand new robust optimal solutions. We believe such robust versions of optimal solutions are potentially more realistic and practical in real world settings.

Synthetic Strategies towards Fullerene-Rich Dendrimer Assemblies

Directory of Open Access Journals (Sweden)

Jean-François Nierengarten

2012-02-01

Full Text Available The sphere-shaped fullerene has attracted considerable interest not least due to the peculiar electronic properties of this carbon allotrope and the fascinating materials emanating from fullerene-derived structures. The rapid development and tremendous advances in organic chemistry allow nowadays the modification of C60 to a great extent by pure chemical means. It is therefore not surprising that the fullerene moiety has also been part of dendrimers. At the initial stage, fullerenes have been examined at the center of the dendritic structure mainly aimed at possible shielding effects as exerted by the dendritic environment and light-harvesting effects due to multiple chromophores located at the periphery of the dendrimer. In recent years, also many research efforts have been devoted towards fullerene-rich nanohybrids containing multiple C60 units in the branches and/or as surface functional groups. In this review, synthetic efforts towards the construction of dendritic fullerene-rich nanostructures have been compiled and will be summarized herein.

Efficient Discovery of Nonlinear Dependencies in a Combinatorial Catalyst Data Set

Czech Academy of Sciences Publication Activity Database

Cawse, J.N.; Baerns, M.; Holeňa, Martin

2004-01-01

Roč. 44, č. 3 (2004), s. 143-146 ISSN 0095-2338 Source of funding: V - iné verejné zdroje Keywords : combinatorial catalysis * genetic algorithms * nonlinear dependency * data analysis * high-order interactions Subject RIV: IN - Informatics, Computer Science Impact factor: 2.810, year: 2004

Sentence Processing in an Artificial Language: Learning and Using Combinatorial Constraints

Science.gov (United States)

Amato, Michael S.; MacDonald, Maryellen C.

2010-01-01

A study combining artificial grammar and sentence comprehension methods investigated the learning and online use of probabilistic, nonadjacent combinatorial constraints. Participants learned a small artificial language describing cartoon monsters acting on objects. Self-paced reading of sentences in the artificial language revealed comprehenders'…

Obfuscation Framework Based on Functionally Equivalent Combinatorial Logic Families

Science.gov (United States)

2008-03-01

of Defense, or the United States Government . AFIT/GCS/ENG/08-12 Obfuscation Framework Based on Functionally Equivalent Combinatorial Logic Families...time, United States policy strongly encourages the sale and transfer of some military equipment to foreign governments and makes it easier for...Proceedings of the International Conference on Availability, Reliability and Security, 2007. 14. McDonald, J. Todd and Alec Yasinsac. “Of unicorns and random

Health Risk Behaviors With Synthetic Cannabinoids Versus Marijuana.

Science.gov (United States)

Clayton, Heather B; Lowry, Richard; Ashley, Carmen; Wolkin, Amy; Grant, Althea M

2017-04-01

Data are limited on the behavioral risk correlates of synthetic cannabinoid use. The purpose of this study was to compare the behavioral risk correlates of synthetic cannabinoid use with those among marijuana users. Data from the 2015 Youth Risk Behavior Survey, a cross-sectional survey conducted in a nationally representative sample of students in grades 9 through 12 ( N = 15 624), were used to examine the association between self-reported type of marijuana use (ie, never use of marijuana and synthetic cannabinoids, ever use of marijuana only, and ever use of synthetic cannabinoids) and self-report of 36 risk behaviors across 4 domains: substance use, injury/violence, mental health, and sexual health. Multivariable models were used to calculate adjusted prevalence ratios. Students who ever used synthetic cannabinoids had a significantly greater likelihood of engaging in each of the behaviors in the substance use and sexual risk domains compared with students who ever used marijuana only. Students who ever used synthetic cannabinoids were more likely than students who ever used marijuana only to have used marijuana before age 13 years, to have used marijuana ≥1 times during the past 30 days, and to have used marijuana ≥20 times during the past 30 days. Several injury/violence behaviors were more prevalent among students who ever used synthetic cannabinoids compared with students who ever used marijuana only. Health professionals and school-based substance use prevention programs should include strategies focused on the prevention of both synthetic cannabinoids and marijuana. Copyright © 2017 by the American Academy of Pediatrics.

Causal gene identification using combinatorial V-structure search.

Science.gov (United States)

Cai, Ruichu; Zhang, Zhenjie; Hao, Zhifeng

2013-07-01

With the advances of biomedical techniques in the last decade, the costs of human genomic sequencing and genomic activity monitoring are coming down rapidly. To support the huge genome-based business in the near future, researchers are eager to find killer applications based on human genome information. Causal gene identification is one of the most promising applications, which may help the potential patients to estimate the risk of certain genetic diseases and locate the target gene for further genetic therapy. Unfortunately, existing pattern recognition techniques, such as Bayesian networks, cannot be directly applied to find the accurate causal relationship between genes and diseases. This is mainly due to the insufficient number of samples and the extremely high dimensionality of the gene space. In this paper, we present the first practical solution to causal gene identification, utilizing a new combinatorial formulation over V-Structures commonly used in conventional Bayesian networks, by exploring the combinations of significant V-Structures. We prove the NP-hardness of the combinatorial search problem under a general settings on the significance measure on the V-Structures, and present a greedy algorithm to find sub-optimal results. Extensive experiments show that our proposal is both scalable and effective, particularly with interesting findings on the causal genes over real human genome data. Copyright © 2013 Elsevier Ltd. All rights reserved.

A combinatorial approach to the design of vaccines.

Science.gov (United States)

Martínez, Luis; Milanič, Martin; Legarreta, Leire; Medvedev, Paul; Malaina, Iker; de la Fuente, Ildefonso M

2015-05-01

We present two new problems of combinatorial optimization and discuss their applications to the computational design of vaccines. In the shortest λ-superstring problem, given a family S1,...,S(k) of strings over a finite alphabet, a set Τ of "target" strings over that alphabet, and an integer λ, the task is to find a string of minimum length containing, for each i, at least λ target strings as substrings of S(i). In the shortest λ-cover superstring problem, given a collection X1,...,X(n) of finite sets of strings over a finite alphabet and an integer λ, the task is to find a string of minimum length containing, for each i, at least λ elements of X(i) as substrings. The two problems are polynomially equivalent, and the shortest λ-cover superstring problem is a common generalization of two well known combinatorial optimization problems, the shortest common superstring problem and the set cover problem. We present two approaches to obtain exact or approximate solutions to the shortest λ-superstring and λ-cover superstring problems: one based on integer programming, and a hill-climbing algorithm. An application is given to the computational design of vaccines and the algorithms are applied to experimental data taken from patients infected by H5N1 and HIV-1.

Combinatorial therapy discovery using mixed integer linear programming.

Science.gov (United States)

Pang, Kaifang; Wan, Ying-Wooi; Choi, William T; Donehower, Lawrence A; Sun, Jingchun; Pant, Dhruv; Liu, Zhandong

2014-05-15

Combinatorial therapies play increasingly important roles in combating complex diseases. Owing to the huge cost associated with experimental methods in identifying optimal drug combinations, computational approaches can provide a guide to limit the search space and reduce cost. However, few computational approaches have been developed for this purpose, and thus there is a great need of new algorithms for drug combination prediction. Here we proposed to formulate the optimal combinatorial therapy problem into two complementary mathematical algorithms, Balanced Target Set Cover (BTSC) and Minimum Off-Target Set Cover (MOTSC). Given a disease gene set, BTSC seeks a balanced solution that maximizes the coverage on the disease genes and minimizes the off-target hits at the same time. MOTSC seeks a full coverage on the disease gene set while minimizing the off-target set. Through simulation, both BTSC and MOTSC demonstrated a much faster running time over exhaustive search with the same accuracy. When applied to real disease gene sets, our algorithms not only identified known drug combinations, but also predicted novel drug combinations that are worth further testing. In addition, we developed a web-based tool to allow users to iteratively search for optimal drug combinations given a user-defined gene set. Our tool is freely available for noncommercial use at http://www.drug.liuzlab.org/. zhandong.liu@bcm.edu Supplementary data are available at Bioinformatics online.

PEG-related polymer resins as synthetic supports

Institute of Scientific and Technical Information of China (English)

无

2010-01-01

Combinatorial chemistry has become a significant part of the discovery and optimization process for novel drugs,affinity ligands,and catalysts.The polymeric supports play a key role in combinatory chemistry.Therefore,various kinds of functional polymer resins have been exploited as supports,reagents,and catalysts in organic synthesis.In comparison to the conventional Merrifield resins,the poly(ethylene glycol)(PEG)-related polymer resins have advantages including good compatibilities with polar solvents,good solvent absorbency and swelling properties.This review focuses primarily on the more recent work in the field of developing PEG-related polymer resins as supports for organic synthesis.

Affinity-based screening of combinatorial libraries using automated, serial-column chromatography

Energy Technology Data Exchange (ETDEWEB)

Evans, D.M.; Williams, K.P.; McGuinness, B. [PerSeptive Biosystems, Framingham, MA (United States)] [and others

1996-04-01

The authors have developed an automated serial chromatographic technique for screening a library of compounds based upon their relative affinity for a target molecule. A {open_quotes}target{close_quotes} column containing the immobilized target molecule is set in tandem with a reversed-phase column. A combinatorial peptide library is injected onto the target column. The target-bound peptides are eluted from the first column and transferred automatically to the reversed-phase column. The target-specific peptide peaks from the reversed-phase column are identified and sequenced. Using a monoclonal antibody (3E-7) against {beta}-endorphin as a target, we selected a single peptide with sequence YGGFL from approximately 5800 peptides present in a combinatorial library. We demonstrated the applicability of the technology towards selection of peptides with predetermined affinity for bacterial lipopolysaccharide (LPS, endotoxin). We expect that this technology will have broad applications for high throughput screening of chemical libraries or natural product extracts. 21 refs., 4 figs.

A Combinatorial Proof of a Result on Generalized Lucas Polynomials

Directory of Open Access Journals (Sweden)

Laugier Alexandre

2016-09-01

Full Text Available We give a combinatorial proof of an elementary property of generalized Lucas polynomials, inspired by [1]. These polynomials in s and t are defined by the recurrence relation 〈n〉 = s〈n-1〉+t〈n-2〉 for n ≥ 2. The initial values are 〈0〉 = 2; 〈1〉= s, respectively.

Combinatorial interpretation of Haldane-Wu fractional exclusion statistics.

Science.gov (United States)

Aringazin, A K; Mazhitov, M I

2002-08-01

Assuming that the maximal allowed number of identical particles in a state is an integer parameter, q, we derive the statistical weight and analyze the associated equation that defines the statistical distribution. The derived distribution covers Fermi-Dirac and Bose-Einstein ones in the particular cases q=1 and q--> infinity (n(i)/q-->1), respectively. We show that the derived statistical weight provides a natural combinatorial interpretation of Haldane-Wu fractional exclusion statistics, and present exact solutions of the distribution equation.

Combinatorial Models for Assembly and Decomposition of Products

OpenAIRE

A. N. Bojko

2015-01-01

The paper discusses the most popular combinatorial models that are used for the synthesis of design solutions at the stage of the assembly process flow preparation. It shows that while assembling the product the relations of parts can be represented as a structure of preferences, which is formed on the basis of objective design restrictions put in at the stage of the product design. This structure is a binary preference relation pre-order. Its symmetrical part is equivalence and describes the...

Synthetic cannabinoid: prevalence, mechanisms of addiction development, mental disorders associated with the use of synthetic cannabinoid

Directory of Open Access Journals (Sweden)

Antsyborov A.V.

2017-04-01

Full Text Available according to the authors among the new psychoactive substances, the number of which is growing every year, despite the measures aimed at the obstacles to their dissemination there discovered the most frequent violations of psychotic conditions associated with use of synthetic cannabinoid in clinical practice. On the black market, they are distributed through online shops, under the guise of herbal mixtures for Smoking. When ingested, this group of drugs at the peak of intoxication raises a number of mental (different according to the depth of impaired consciousness, auditory and visual hallucinations, panic attacks, acute psychotic paranoid disorders, catatonic stupor, polar affective disorders, acute polythematic delusional symptoms and somatic disorders (disorders of heart rhythm and conduction, acute ischemic disorders, hypertension, depression of respiratory activity, violation of thermoregulation, development of acute renal failure, vomiting, expressed cephalgia, clinic of hypokalemia. In the reviewed literature and authors own observations there have been discovered some cases of mental addiction development to synthetic cannabinoids. The analysis of new literature data and own clinical observations helped the authors to compare the psychotropic effects caused by this group of drugs, relative to other known surfactants. The toxic effects of CSC on the body greatly exceeds the use of plant cannabinoids, and it has almost the same effects as the synthetic cathinone’s. The speed of formation of psychological dependence is lower compared to synthetic cathinone. Developing current strategies for diagnosis, treatment, and rehabilitation of patients who use synthetic cannabinoids remains an important task for practical healthcare.

Editorial: Cologne/Twente workshop on graphs and combinatorial optimization CTW 2007

NARCIS (Netherlands)

Faigle, U.; Hurink, Johann L.

2010-01-01

The 6th Cologne-Twente Workshop on Graphs and Combinatorial Optimization (CTW 2007) was held at the University of Twente, The Netherlands, 29-31 May, 2007. The CTW started as a series of biennial meetings at the Universities of Cologne in Germany and Twente in the Netherlands. Ever increasing

Natural - synthetic - artificial!

DEFF Research Database (Denmark)

Nielsen, Peter E

2010-01-01

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

Hierarchical Bayesian mixture modelling for antigen-specific T-cell subtyping in combinatorially encoded flow cytometry studies

DEFF Research Database (Denmark)

Lin, Lin; Chan, Cliburn; Hadrup, Sine R

2013-01-01

subtype identification in this novel, general model framework, and provide a detailed example using simulated data. We then describe application to a data set from an experimental study of antigen-specific T-cell subtyping using combinatorially encoded assays in human blood samples. Summary comments...... profiling in many biological areas, traditional flow cytometry measures relative levels of abundance of marker proteins using fluorescently labeled tags that identify specific markers by a single-color. One specific and important recent development in this area is the use of combinatorial marker assays...

Particle Swarm Optimization applied to combinatorial problem aiming the fuel recharge problem solution in a nuclear reactor

International Nuclear Information System (INIS)

Meneses, Anderson Alvarenga de Moura; Schirru, Roberto

2005-01-01

This work focuses on the usage the Artificial Intelligence technique Particle Swarm Optimization (PSO) to optimize the fuel recharge at a nuclear reactor. This is a combinatorial problem, in which the search of the best feasible solution is done by minimizing a specific objective function. However, in this first moment it is possible to compare the fuel recharge problem with the Traveling Salesman Problem (TSP), since both of them are combinatorial, with one advantage: the evaluation of the TSP objective function is much more simple. Thus, the proposed methods have been applied to two TSPs: Oliver 30 and Rykel 48. In 1995, KENNEDY and EBERHART presented the PSO technique to optimize non-linear continued functions. Recently some PSO models for discrete search spaces have been developed for combinatorial optimization. Although all of them having different formulation from the ones presented here. In this paper, we use the PSO theory associated with to the Random Keys (RK)model, used in some optimizations with Genetic Algorithms. The Particle Swarm Optimization with Random Keys (PSORK) results from this association, which combines PSO and RK. The adaptations and changings in the PSO aim to allow the usage of the PSO at the nuclear fuel recharge. This work shows the PSORK being applied to the proposed combinatorial problem and the obtained results. (author)

Rapid isolation of antibody from a synthetic human antibody library by repeated fluorescence-activated cell sorting (FACS.

Directory of Open Access Journals (Sweden)

Sung Sun Yim

Full Text Available Antibodies and their derivatives are the most important agents in therapeutics and diagnostics. Even after the significant progress in the technology for antibody screening from huge libraries, it takes a long time to isolate an antibody, which prevents a prompt action against the spread of a disease. Here, we report a new strategy for isolating desired antibodies from a combinatorial library in one day by repeated fluorescence-activated cell sorting (FACS. First, we constructed a library of synthetic human antibody in which single-chain variable fragment (scFv was expressed in the periplasm of Escherichia coli. After labeling the cells with fluorescent antigen probes, the highly fluorescent cells were sorted by using a high-speed cell sorter, and these cells were reused without regeneration in the next round of sorting. After repeating this sorting, the positive clones were completely enriched in several hours. Thus, we screened the library against three viral antigens, including the H1N1 influenza virus, Hepatitis B virus, and Foot-and-mouth disease virus. Finally, the potential antibody candidates, which show K(D values between 10 and 100 nM against the target antigens, could be successfully isolated even though the library was relatively small (∼ 10(6. These results show that repeated FACS screening without regeneration of the sorted cells can be a powerful method when a rapid response to a spreading disease is required.

[Applications of synthetic biology in materials science].

Science.gov (United States)

Zhao, Tianxin; Zhong, Chao

2017-03-25

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

Complexity and Tractability Islands for Combinatorial Auctions on Discrete Intervals with Gaps

NARCIS (Netherlands)

Döcker, J.; Dorn, B.; Endriss, U.; Krüger, D.; Kaminka, G.A.; Fox, M.; Bouquet, P.; Hüllermeyer, E.; Dignum, V.; Dignum, F.; van Harmelen, F.

2016-01-01

Combinatorial auctions are mechanisms for allocating bundles of goods to agents who each have preferences over these goods. Finding an economically efficient allocation, the so-called winner determination problem, is computationally intractable in the general case, which is why it is important to

COGEDIF - automatic TORT and DORT input generation from MORSE combinatorial geometry models

International Nuclear Information System (INIS)

Castelli, R.A.; Barnett, D.A.

1992-01-01

COGEDIF is an interactive utility which was developed to automate the preparation of two and three dimensional geometrical inputs for the ORNL-TORT and DORT discrete ordinates programs from complex three dimensional models described using the MORSE combinatorial geometry input description. The program creates either continuous or disjoint mesh input based upon the intersections of user defined meshing planes and the MORSE body definitions. The composition overlay of the combinatorial geometry is used to create the composition mapping of the discretized geometry based upon the composition found at the centroid of each of the mesh cells. This program simplifies the process of using discrete orthogonal mesh cells to represent non-orthogonal geometries in large models which require mesh sizes of the order of a million cells or more. The program was specifically written to take advantage of the new TORT disjoint mesh option which was developed at ORNL

From combinatorial optimization to real algebraic geometry and back

Directory of Open Access Journals (Sweden)

Janez Povh

2014-12-01

Full Text Available In this paper, we explain the relations between combinatorial optimization and real algebraic geometry with a special focus to the quadratic assignment problem. We demonstrate how to write a quadratic optimization problem over discrete feasible set as a linear optimization problem over the cone of completely positive matrices. The latter formulation enables a hierarchy of approximations which rely on results from polynomial optimization, a sub-eld of real algebraic geometry.

Combinatorial discovery of new methanol-tolerant non-noble metal cathode electrocatalysts for direct methanol fuel cells.

Science.gov (United States)

Yu, Jong-Sung; Kim, Min-Sik; Kim, Jung Ho

2010-12-14

Combinatorial synthesis and screening were used to identify methanol-tolerant non-platinum cathode electrocatalysts for use in direct methanol fuel cells (DMFCs). Oxygen reduction consumes protons at the surface of DMFC cathode catalysts. In combinatorial screening, this pH change allows one to differentiate active catalysts using fluorescent acid-base indicators. Combinatorial libraries of carbon-supported catalyst compositions containing Ru, Mo, W, Sn, and Se were screened. Ternary and quaternary compositions containing Ru, Sn, Mo, Se were more active than the "standard" Alonso-Vante catalyst, Ru(3)Mo(0.08)Se(2), when tested in liquid-feed DMFCs. Physical characterization of the most active catalysts by powder X-ray diffraction, gas adsorption, and X-ray photoelectron spectroscopy revealed that the predominant crystalline phase was hexagonal close-packed (hcp) ruthenium, and showed a surface mostly covered with oxide. The best new catalyst, Ru(7.0)Sn(1.0)Se(1.0), was significantly more active than Ru(3)Se(2)Mo(0.08), even though the latter contained smaller particles.

Template-based combinatorial enumeration of virtual compound libraries for lipids.

Science.gov (United States)

Sud, Manish; Fahy, Eoin; Subramaniam, Shankar

2012-09-25

A variety of software packages are available for the combinatorial enumeration of virtual libraries for small molecules, starting from specifications of core scaffolds with attachments points and lists of R-groups as SMILES or SD files. Although SD files include atomic coordinates for core scaffolds and R-groups, it is not possible to control 2-dimensional (2D) layout of the enumerated structures generated for virtual compound libraries because different packages generate different 2D representations for the same structure. We have developed a software package called LipidMapsTools for the template-based combinatorial enumeration of virtual compound libraries for lipids. Virtual libraries are enumerated for the specified lipid abbreviations using matching lists of pre-defined templates and chain abbreviations, instead of core scaffolds and lists of R-groups provided by the user. 2D structures of the enumerated lipids are drawn in a specific and consistent fashion adhering to the framework for representing lipid structures proposed by the LIPID MAPS consortium. LipidMapsTools is lightweight, relatively fast and contains no external dependencies. It is an open source package and freely available under the terms of the modified BSD license.

Combinatorial One-Pot Synthesis of Poly-N-acetyllactosamine Oligosaccharides with Leloir-Glycosyltransferases

Czech Academy of Sciences Publication Activity Database

Rech, C.; Rosencrantz, R. R.; Křenek, Karel; Pelantová, Helena; Bojarová, Pavla; Roemer, Ch. E.; Hanisch, F.-G.; Křen, Vladimír; Elling, L.

2011-01-01

Roč. 353, č. 13 (2011), s. 2492-2500 ISSN 1615-4150 R&D Projects: GA MŠk OC09045 Institutional research plan: CEZ:AV0Z50200510 Keywords : combinatorial chemistry * biocatalysis * carbohydrates Subject RIV: CC - Organic Chemistry Impact factor: 6.048, year: 2011

A model-based combinatorial optimisation approach for energy-efficient processing of microalgae

NARCIS (Netherlands)

Slegers, P.M.; Koetzier, B.J.; Fasaei, F.; Wijffels, R.H.; Straten, van G.; Boxtel, van A.J.B.

2014-01-01

The analyses of algae biorefinery performance are commonly based on fixed performance data for each processing step. In this work, we demonstrate a model-based combinatorial approach to derive the design-specific upstream energy consumption and biodiesel yield in the production of biodiesel from

Combinatorial synthesis of oxazol-thiazole bis-heterocyclic compounds.

Science.gov (United States)

Murru, Siva; Nefzi, Adel

2014-01-13

A combinatorial library of novel oxazol-thiazole bis-heterocycles was synthesized in good to excellent overall yields with high purity using a solution and solid-phase parallel synthesis approach. Oxazole amino acids, prepared from serine methyl ester and amino acids via coupling and cyclodehydration, were treated with Fmoc-NCS and α-haloketones for the parallel synthesis of diverse bis-heterocycles. Fmoc-isothiocyanate is used as a traceless reagent for thiazole formation. Oxazole diversity can be achieved by using variety of amino acids, whereas thiazole diversity is produced with various haloketones.

Proceedings of the 8th Nordic Combinatorial Conference

DEFF Research Database (Denmark)

Geil, Olav; Andersen, Lars Døvling

The Nordic Combinatorial Conferences were initiated in 1981 by mathematicians from Stavanger. Held approximately every three years since then, the conferences have been able to sustain the interest from combinatorialists all over the Nordic countries. In 2004 the 8th conference is held in Aalborg......, Denmark. We are pleased that so many people have chosen to attend, and that lectures were offered from more participants than we had originally reserved time for. We asked two mathematicians to give special lectures and are happy that both accepted immediately. Andries Brouwer from the Technical...

Estimating meme fitness in adaptive memetic algorithms for combinatorial problems.

Science.gov (United States)

Smith, J E

2012-01-01

Among the most promising and active research areas in heuristic optimisation is the field of adaptive memetic algorithms (AMAs). These gain much of their reported robustness by adapting the probability with which each of a set of local improvement operators is applied, according to an estimate of their current value to the search process. This paper addresses the issue of how the current value should be estimated. Assuming the estimate occurs over several applications of a meme, we consider whether the extreme or mean improvements should be used, and whether this aggregation should be global, or local to some part of the solution space. To investigate these issues, we use the well-established COMA framework that coevolves the specification of a population of memes (representing different local search algorithms) alongside a population of candidate solutions to the problem at hand. Two very different memetic algorithms are considered: the first using adaptive operator pursuit to adjust the probabilities of applying a fixed set of memes, and a second which applies genetic operators to dynamically adapt and create memes and their functional definitions. For the latter, especially on combinatorial problems, credit assignment mechanisms based on historical records, or on notions of landscape locality, will have limited application, and it is necessary to estimate the value of a meme via some form of sampling. The results on a set of binary encoded combinatorial problems show that both methods are very effective, and that for some problems it is necessary to use thousands of variables in order to tease apart the differences between different reward schemes. However, for both memetic algorithms, a significant pattern emerges that reward based on mean improvement is better than that based on extreme improvement. This contradicts recent findings from adapting the parameters of operators involved in global evolutionary search. The results also show that local reward schemes

Dynamic Hierarchical Energy-Efficient Method Based on Combinatorial Optimization for Wireless Sensor Networks.

Science.gov (United States)

Chang, Yuchao; Tang, Hongying; Cheng, Yongbo; Zhao, Qin; Yuan, Baoqing Li andXiaobing

2017-07-19

Routing protocols based on topology control are significantly important for improving network longevity in wireless sensor networks (WSNs). Traditionally, some WSN routing protocols distribute uneven network traffic load to sensor nodes, which is not optimal for improving network longevity. Differently to conventional WSN routing protocols, we propose a dynamic hierarchical protocol based on combinatorial optimization (DHCO) to balance energy consumption of sensor nodes and to improve WSN longevity. For each sensor node, the DHCO algorithm obtains the optimal route by establishing a feasible routing set instead of selecting the cluster head or the next hop node. The process of obtaining the optimal route can be formulated as a combinatorial optimization problem. Specifically, the DHCO algorithm is carried out by the following procedures. It employs a hierarchy-based connection mechanism to construct a hierarchical network structure in which each sensor node is assigned to a special hierarchical subset; it utilizes the combinatorial optimization theory to establish the feasible routing set for each sensor node, and takes advantage of the maximum-minimum criterion to obtain their optimal routes to the base station. Various results of simulation experiments show effectiveness and superiority of the DHCO algorithm in comparison with state-of-the-art WSN routing algorithms, including low-energy adaptive clustering hierarchy (LEACH), hybrid energy-efficient distributed clustering (HEED), genetic protocol-based self-organizing network clustering (GASONeC), and double cost function-based routing (DCFR) algorithms.

A binary plasmid system for shuffling combinatorial antibody libraries.

OpenAIRE

Collet, T A; Roben, P; O'Kennedy, R; Barbas, C F; Burton, D R; Lerner, R A

1992-01-01

We have used a binary system of replicon-compatible plasmids to test the potential for promiscuous recombination of heavy and light chains within sets of human Fab fragments isolated from combinatorial antibody libraries. Antibody molecules showed a surprising amount of promiscuity in that a particular heavy chain could recombine with multiple light chains with retention of binding to a protein antigen. The degree to which a given heavy chain productively paired with any light chain to bind a...

High-throughput combinatorial chemical bath deposition: The case of doping Cu (In, Ga) Se film with antimony

Science.gov (United States)

Yan, Zongkai; Zhang, Xiaokun; Li, Guang; Cui, Yuxing; Jiang, Zhaolian; Liu, Wen; Peng, Zhi; Xiang, Yong

2018-01-01

The conventional methods for designing and preparing thin film based on wet process remain a challenge due to disadvantages such as time-consuming and ineffective, which hinders the development of novel materials. Herein, we present a high-throughput combinatorial technique for continuous thin film preparation relied on chemical bath deposition (CBD). The method is ideally used to prepare high-throughput combinatorial material library with low decomposition temperatures and high water- or oxygen-sensitivity at relatively high-temperature. To check this system, a Cu(In, Ga)Se (CIGS) thin films library doped with 0-19.04 at.% of antimony (Sb) was taken as an example to evaluate the regulation of varying Sb doping concentration on the grain growth, structure, morphology and electrical properties of CIGS thin film systemically. Combined with the Energy Dispersive Spectrometer (EDS), X-ray Photoelectron Spectroscopy (XPS), automated X-ray Diffraction (XRD) for rapid screening and Localized Electrochemical Impedance Spectroscopy (LEIS), it was confirmed that this combinatorial high-throughput system could be used to identify the composition with the optimal grain orientation growth, microstructure and electrical properties systematically, through accurately monitoring the doping content and material composition. According to the characterization results, a Sb2Se3 quasi-liquid phase promoted CIGS film-growth model has been put forward. In addition to CIGS thin film reported here, the combinatorial CBD also could be applied to the high-throughput screening of other sulfide thin film material systems.

Middle-down hybrid chromatography/tandem mass spectrometry workflow for characterization of combinatorial post-translational modifications in histones.

Science.gov (United States)

Sidoli, Simone; Schwämmle, Veit; Ruminowicz, Chrystian; Hansen, Thomas A; Wu, Xudong; Helin, Kristian; Jensen, Ole N

2014-10-01

We present an integrated middle-down proteomics platform for sensitive mapping and quantification of coexisting PTMs in large polypeptides (5-7 kDa). We combined an RP trap column with subsequent weak cation exchange-hydrophilic interaction LC interfaced directly to high mass accuracy ESI MS/MS using electron transfer dissociation. This enabled automated and efficient separation and sequencing of hypermodified histone N-terminal tails for unambiguous localization of combinatorial PTMs. We present Histone Coder and IsoScale software to extract, filter, and analyze MS/MS data, including quantification of cofragmenting isobaric polypeptide species. We characterized histone tails derived from murine embryonic stem cells knockout in suppressor of zeste12 (Suz12(-/-) ) and quantified 256 combinatorial histone marks in histones H3, H4, and H2A. Furthermore, a total of 713 different combinatorial histone marks were identified in purified histone H3. We measured a seven-fold reduction of H3K27me2/me3 (where me2 and me3 are dimethylation and trimethylation, respectively) in Suz12(-) (/) (-) cells and detected significant changes of the relative abundance of 16 other single PTMs of histone H3 and other combinatorial marks. We conclude that the inactivation of Suz12 is associated with changes in the abundance of not only H3K27 methylation but also multiple other PTMs in histone H3 tails. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Fragment Linking and Optimization of Inhibitors of the Aspartic Protease Endothiapepsin: Fragment‐Based Drug Design Facilitated by Dynamic Combinatorial Chemistry

Science.gov (United States)

Mondal, Milon; Radeva, Nedyalka; Fanlo‐Virgós, Hugo; Otto, Sijbren; Klebe, Gerhard

2016-01-01

Abstract Fragment‐based drug design (FBDD) affords active compounds for biological targets. While there are numerous reports on FBDD by fragment growing/optimization, fragment linking has rarely been reported. Dynamic combinatorial chemistry (DCC) has become a powerful hit‐identification strategy for biological targets. We report the synergistic combination of fragment linking and DCC to identify inhibitors of the aspartic protease endothiapepsin. Based on X‐ray crystal structures of endothiapepsin in complex with fragments, we designed a library of bis‐acylhydrazones and used DCC to identify potent inhibitors. The most potent inhibitor exhibits an IC50 value of 54 nm, which represents a 240‐fold improvement in potency compared to the parent hits. Subsequent X‐ray crystallography validated the predicted binding mode, thus demonstrating the efficiency of the combination of fragment linking and DCC as a hit‐identification strategy. This approach could be applied to a range of biological targets, and holds the potential to facilitate hit‐to‐lead optimization. PMID:27400756

Enumeration of smallest intervention strategies in genome-scale metabolic networks.

Directory of Open Access Journals (Sweden)

Axel von Kamp

2014-01-01

Full Text Available One ultimate goal of metabolic network modeling is the rational redesign of biochemical networks to optimize the production of certain compounds by cellular systems. Although several constraint-based optimization techniques have been developed for this purpose, methods for systematic enumeration of intervention strategies in genome-scale metabolic networks are still lacking. In principle, Minimal Cut Sets (MCSs; inclusion-minimal combinations of reaction or gene deletions that lead to the fulfilment of a given intervention goal provide an exhaustive enumeration approach. However, their disadvantage is the combinatorial explosion in larger networks and the requirement to compute first the elementary modes (EMs which itself is impractical in genome-scale networks. We present MCSEnumerator, a new method for effective enumeration of the smallest MCSs (with fewest interventions in genome-scale metabolic network models. For this we combine two approaches, namely (i the mapping of MCSs to EMs in a dual network, and (ii a modified algorithm by which shortest EMs can be effectively determined in large networks. In this way, we can identify the smallest MCSs by calculating the shortest EMs in the dual network. Realistic application examples demonstrate that our algorithm is able to list thousands of the most efficient intervention strategies in genome-scale networks for various intervention problems. For instance, for the first time we could enumerate all synthetic lethals in E.coli with combinations of up to 5 reactions. We also applied the new algorithm exemplarily to compute strain designs for growth-coupled synthesis of different products (ethanol, fumarate, serine by E.coli. We found numerous new engineering strategies partially requiring less knockouts and guaranteeing higher product yields (even without the assumption of optimal growth than reported previously. The strength of the presented approach is that smallest intervention strategies can be

Combinatorial identities for Stirling numbers the unpublished notes of H. W. Gould

CERN Document Server

Quaintance, Jocelyn

2016-01-01

This book is a unique work which provides an in-depth exploration into the mathematical expertise, philosophy, and knowledge of H W Gould. It is written in a style that is accessible to the reader with basic mathematical knowledge, and yet contains material that will be of interest to the specialist in enumerative combinatorics. This book begins with exposition on the combinatorial and algebraic techniques that Professor Gould uses for proving binomial identities. These techniques are then applied to develop formulas which relate Stirling numbers of the second kind to Stirling numbers of the first kind. Professor Gould's techniques also provide connections between both types of Stirling numbers and Bernoulli numbers. Professor Gould believes his research success comes from his intuition on how to discover combinatorial identities.This book will appeal to a wide audience and may be used either as lecture notes for a beginning graduate level combinatorics class, or as a research supplement for the specialist in...

Cisplatin nephrotoxicity: mechanisms and renoprotective strategies.

Science.gov (United States)

Pabla, N; Dong, Z

2008-05-01

Cisplatin is one of the most widely used and most potent chemotherapy drugs. However, side effects in normal tissues and organs, notably nephrotoxicity in the kidneys, limit the use of cisplatin and related platinum-based therapeutics. Recent research has shed significant new lights on the mechanism of cisplatin nephrotoxicity, especially on the signaling pathways leading to tubular cell death and inflammation. Renoprotective approaches are being discovered, but the protective effects are mostly partial, suggesting the need for combinatorial strategies. Importantly, it is unclear whether these approaches would limit the anticancer effects of cisplatin in tumors. Examination of tumor-bearing animals and identification of novel renoprotective strategies that do not diminish the anticancer efficacy of cisplatin are essential to the development of clinically applicable interventions.

Hospital daily outpatient visits forecasting using a combinatorial model based on ARIMA and SES models.

Science.gov (United States)

Luo, Li; Luo, Le; Zhang, Xinli; He, Xiaoli

2017-07-10

Accurate forecasting of hospital outpatient visits is beneficial for the reasonable planning and allocation of healthcare resource to meet the medical demands. In terms of the multiple attributes of daily outpatient visits, such as randomness, cyclicity and trend, time series methods, ARIMA, can be a good choice for outpatient visits forecasting. On the other hand, the hospital outpatient visits are also affected by the doctors' scheduling and the effects are not pure random. Thinking about the impure specialty, this paper presents a new forecasting model that takes cyclicity and the day of the week effect into consideration. We formulate a seasonal ARIMA (SARIMA) model on a daily time series and then a single exponential smoothing (SES) model on the day of the week time series, and finally establish a combinatorial model by modifying them. The models are applied to 1 year of daily visits data of urban outpatients in two internal medicine departments of a large hospital in Chengdu, for forecasting the daily outpatient visits about 1 week ahead. The proposed model is applied to forecast the cross-sectional data for 7 consecutive days of daily outpatient visits over an 8-weeks period based on 43 weeks of observation data during 1 year. The results show that the two single traditional models and the combinatorial model are simplicity of implementation and low computational intensiveness, whilst being appropriate for short-term forecast horizons. Furthermore, the combinatorial model can capture the comprehensive features of the time series data better. Combinatorial model can achieve better prediction performance than the single model, with lower residuals variance and small mean of residual errors which needs to be optimized deeply on the next research step.

Performance analysis of demodulation with diversity -- A combinatorial approach I: Symmetric function theoretical methods

OpenAIRE

Jean-Louis Dornstetter; Daniel Krob; Jean-Yves Thibon; Ekaterina A. Vassilieva

2002-01-01

This paper is devoted to the presentation of a combinatorial approach, based on the theory of symmetric functions, for analyzing the performance of a family of demodulation methods used in mobile telecommunications.

Seismic microzoning from synthetic ground motion parameters Case study, Santiago de Cuba

CERN Document Server

Alvarez, L; Pico, R; Vaccari, F

2003-01-01

Synthetic seismograms (P - SV and SH waves) have been calculated along 6 profiles in Santiago de Cuba basin, with a cutoff frequency of 5 Hz, by using the hybrid approach (modal summation for a regional (ID) structure plus finite differences for a local (2D) structure embedded in the first). They correspond to a scenario earthquake of M sub S = 7 that may occur in Oriente fault zone, directly south of the city. As initial data for a seismic microzoning, the characterisation of earthquake effects has been made considering several relative (2D/1D) quantities (PGDR, PGVR, PGAR, DGAR, I sub A R etc.) and functions representative of the ground motion behaviour in soil (2D) with respect to bedrock (ID). The functions are the response spectra ratio RSR(f), already routinely used in this kind of work, and the elastic energy input ratio E sub I R(f), defined, for the first time, in this paper. These data, sampled at 105 sites within all the profiles have been classified in two steps, using logical combinatory algorith...

Combinatorial Pharmacophore-Based 3D-QSAR Analysis and Virtual Screening of FGFR1 Inhibitors

Directory of Open Access Journals (Sweden)

Nannan Zhou

2015-06-01

Full Text Available The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR signaling pathway plays crucial roles in cell proliferation, angiogenesis, migration, and survival. Aberration in FGFRs correlates with several malignancies and disorders. FGFRs have proved to be attractive targets for therapeutic intervention in cancer, and it is of high interest to find FGFR inhibitors with novel scaffolds. In this study, a combinatorial three-dimensional quantitative structure-activity relationship (3D-QSAR model was developed based on previously reported FGFR1 inhibitors with diverse structural skeletons. This model was evaluated for its prediction performance on a diverse test set containing 232 FGFR inhibitors, and it yielded a SD value of 0.75 pIC50 units from measured inhibition affinities and a Pearson’s correlation coefficient R2 of 0.53. This result suggests that the combinatorial 3D-QSAR model could be used to search for new FGFR1 hit structures and predict their potential activity. To further evaluate the performance of the model, a decoy set validation was used to measure the efficiency of the model by calculating EF (enrichment factor. Based on the combinatorial pharmacophore model, a virtual screening against SPECS database was performed. Nineteen novel active compounds were successfully identified, which provide new chemical starting points for further structural optimization of FGFR1 inhibitors.

Intrinsic information carriers in combinatorial dynamical systems

Science.gov (United States)

Harmer, Russ; Danos, Vincent; Feret, Jérôme; Krivine, Jean; Fontana, Walter

2010-09-01

Many proteins are composed of structural and chemical features—"sites" for short—characterized by definite interaction capabilities, such as noncovalent binding or covalent modification of other proteins. This modularity allows for varying degrees of independence, as the behavior of a site might be controlled by the state of some but not all sites of the ambient protein. Independence quickly generates a startling combinatorial complexity that shapes most biological networks, such as mammalian signaling systems, and effectively prevents their study in terms of kinetic equations—unless the complexity is radically trimmed. Yet, if combinatorial complexity is key to the system's behavior, eliminating it will prevent, not facilitate, understanding. A more adequate representation of a combinatorial system is provided by a graph-based framework of rewrite rules where each rule specifies only the information that an interaction mechanism depends on. Unlike reactions, which deal with molecular species, rules deal with patterns, i.e., multisets of molecular species. Although the stochastic dynamics induced by a collection of rules on a mixture of molecules can be simulated, it appears useful to capture the system's average or deterministic behavior by means of differential equations. However, expansion of the rules into kinetic equations at the level of molecular species is not only impractical, but conceptually indefensible. If rules describe bona fide patterns of interaction, molecular species are unlikely to constitute appropriate units of dynamics. Rather, we must seek aggregate variables reflective of the causal structure laid down by the rules. We call these variables "fragments" and the process of identifying them "fragmentation." Ideally, fragments are aspects of the system's microscopic population that the set of rules can actually distinguish on average; in practice, it may only be feasible to identify an approximation to this. Most importantly, fragments are

Intrinsic information carriers in combinatorial dynamical systems.

Science.gov (United States)

Harmer, Russ; Danos, Vincent; Feret, Jérôme; Krivine, Jean; Fontana, Walter

2010-09-01

Many proteins are composed of structural and chemical features--"sites" for short--characterized by definite interaction capabilities, such as noncovalent binding or covalent modification of other proteins. This modularity allows for varying degrees of independence, as the behavior of a site might be controlled by the state of some but not all sites of the ambient protein. Independence quickly generates a startling combinatorial complexity that shapes most biological networks, such as mammalian signaling systems, and effectively prevents their study in terms of kinetic equations-unless the complexity is radically trimmed. Yet, if combinatorial complexity is key to the system's behavior, eliminating it will prevent, not facilitate, understanding. A more adequate representation of a combinatorial system is provided by a graph-based framework of rewrite rules where each rule specifies only the information that an interaction mechanism depends on. Unlike reactions, which deal with molecular species, rules deal with patterns, i.e., multisets of molecular species. Although the stochastic dynamics induced by a collection of rules on a mixture of molecules can be simulated, it appears useful to capture the system's average or deterministic behavior by means of differential equations. However, expansion of the rules into kinetic equations at the level of molecular species is not only impractical, but conceptually indefensible. If rules describe bona fide patterns of interaction, molecular species are unlikely to constitute appropriate units of dynamics. Rather, we must seek aggregate variables reflective of the causal structure laid down by the rules. We call these variables "fragments" and the process of identifying them "fragmentation." Ideally, fragments are aspects of the system's microscopic population that the set of rules can actually distinguish on average; in practice, it may only be feasible to identify an approximation to this. Most importantly, fragments are

Transcriptional reprogramming in yeast using dCas9 and combinatorial gRNA strategies

DEFF Research Database (Denmark)

Damgaard Jensen, Emil; Ferreira, Raphael; Jakociunas, Tadas

2017-01-01

on developing synthetic biology tools for orthogonal control of transcription. Most recently, the nuclease-deficient Cas9 (dCas9) has emerged as a flexible tool for controlling activation and repression of target genes, by the simple RNA-guided positioning of dCas9 in the vicinity of the target gene...... transcription start site. In this study we compared two different systems of dCas9-mediated transcriptional reprogramming, and applied them to genes controlling two biosynthetic pathways for biobased production of isoprenoids and triacylglycerols (TAGs) in baker's yeast Saccharomyces cerevisiae. By testing 101...... production and increases in TAG. Taken together, we show similar performance for a constitutive and an inducible dCas9 approach, and identify multiplex gRNA designs that can significantly perturb isoprenoid production and TAG profiles in yeast without editing the genomic context of the target genes. We also...

The Prion Concept and Synthetic Prions.

Science.gov (United States)

Legname, Giuseppe; Moda, Fabio

2017-01-01

Transmissible spongiform encephalopathies or prion diseases are a group of fatal neurodegenerative diseases caused by unconventional infectious agents, known as prions (PrP Sc ). Prions derive from a conformational conversion of the normally folded prion protein (PrP C ), which acquires pathological and infectious features. Moreover, PrP Sc is able to transmit the pathological conformation to PrP C through a mechanism that is still not well understood. The generation of synthetic prions, which behave like natural prions, is of fundamental importance to study the process of PrP C conversion and to assess the efficacy of therapeutic strategies to interfere with this process. Moreover, the ability of synthetic prions to induce pathology in animals confirms that the pathological properties of the prion strains are all enciphered in abnormal conformations, characterizing these infectious agents. © 2017 Elsevier Inc. All rights reserved.

Combinatorial nanomedicines for colon cancer therapy.

Science.gov (United States)

Anitha, A; Maya, S; Sivaram, Amal J; Mony, U; Jayakumar, R

2016-01-01

Colon cancer is one of the major causes of cancer deaths worldwide. Even after surgical resection and aggressive chemotherapy, 50% of colorectal carcinoma patients develop recurrent disease. Thus, the rationale of developing new therapeutic approaches to improve the current chemotherapeutic regimen would be highly recommended. There are reports on the effectiveness of combination chemotherapy in colon cancer and it has been practiced in clinics for long time. These approaches are associated with toxic side effects. Later, the drug delivery research had shown the potential of nanoencapsulation techniques and active targeting as an effective method to improve the effectiveness of chemotherapy with less toxicity. This current focus article provides a brief analysis of the ongoing research in the colon cancer area using the combinatorial nanomedicines and its outcome. © 2015 Wiley Periodicals, Inc.

Synthetic Cannabinoids

Directory of Open Access Journals (Sweden)

Aslihan Okan Ibiloglu

2017-09-01

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

Hybrid protein-synthetic polymer nanoparticles for drug delivery.

Science.gov (United States)

Koseva, Neli S; Rydz, Joanna; Stoyanova, Ekaterina V; Mitova, Violeta A

2015-01-01

Among the most common nanoparticulate systems, the polymeric nanocarriers have a number of key benefits, which give a great choice of delivery platforms. Nevertheless, polymeric nanoparticles possess some limitations that include use of toxic solvents in the production process, polymer degradation, drug leakage outside the diseased tissue, and polymer cytotoxicity. The combination of polymers of biological and synthetic origin is an appealing modern strategy for the production of novel nanocarriers with unprecedented properties. Proteins' interface can play an important role in determining bioactivity and toxicity and gives perspective for future development of the polymer-based nanoparticles. The design of hybrid constructs composed of synthetic polymer and biological molecules such as proteins can be considered as a straightforward tool to integrate a broad spectrum of properties and biofunctions into a single device. This review discusses hybrid protein-synthetic polymer nanoparticles with different structures and levels in complexity and functionality, in view of their applications as drug delivery systems. © 2015 Elsevier Inc. All rights reserved.

A combinatorial proof of Postnikov's identity and a generalized enumeration of labeled trees

OpenAIRE

Seo, Seunghyun

2004-01-01

In this paper, we give a simple combinatorial explanation of a formula of A. Postnikov relating bicolored rooted trees to bicolored binary trees. We also present generalized formulas for the number of labeled k-ary trees, rooted labeled trees, and labeled plane trees.

Parameter Estimation of Permanent Magnet Synchronous Motor Using Orthogonal Projection and Recursive Least Squares Combinatorial Algorithm

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Iman Yousefi

2015-01-01

Full Text Available This paper presents parameter estimation of Permanent Magnet Synchronous Motor (PMSM using a combinatorial algorithm. Nonlinear fourth-order space state model of PMSM is selected. This model is rewritten to the linear regression form without linearization. Noise is imposed to the system in order to provide a real condition, and then combinatorial Orthogonal Projection Algorithm and Recursive Least Squares (OPA&RLS method is applied in the linear regression form to the system. Results of this method are compared to the Orthogonal Projection Algorithm (OPA and Recursive Least Squares (RLS methods to validate the feasibility of the proposed method. Simulation results validate the efficacy of the proposed algorithm.

Performance analysis of demodulation with diversity -- A combinatorial approach I: Symmetric function theoretical methods

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Jean-Louis Dornstetter

2002-12-01

Full Text Available This paper is devoted to the presentation of a combinatorial approach, based on the theory of symmetric functions, for analyzing the performance of a family of demodulation methods used in mobile telecommunications.

Synthetic Biology to Engineer Bacteriophage Genomes.

Science.gov (United States)

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

2018-01-01

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

[From synthetic biology to synthetic humankind].

Science.gov (United States)

Nouvel, Pascal

2015-01-01

In this paper, we propose an historical survey of the expression "synthetic biology" in order to identify its main philosophical components. The result of the analysis is then used to investigate the meaning of the notion of "synthetic man". It is shown that both notions share a common philosophical background that can be summed up by the short but meaningful assertion: "biology is technology". The analysis allows us to distinguish two notions that are often confused in transhumanist literature: the notion of synthetic man and the notion of renewed man. The consequences of this crucial distinction are discussed. Copyright © 2015 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Rational synthetic pathway refactoring of natural products biosynthesis in actinobacteria.

Science.gov (United States)

Tan, Gao-Yi; Liu, Tiangang

2017-01-01

Natural products (NPs) and their derivatives are widely used as frontline treatments for many diseases. Actinobacteria spp. are used to produce most of NP antibiotics and have also been intensively investigated for NP production, derivatization, and discovery. However, due to the complicated transcriptional and metabolic regulation of NP biosynthesis in Actinobacteria, especially in the cases of genome mining and heterologous expression, it is often difficult to rationally and systematically engineer synthetic pathways to maximize biosynthetic efficiency. With the emergence of new tools and methods in metabolic engineering, the synthetic pathways of many chemicals, such as fatty acids and biofuels, in model organisms (e.g. Escherichia coli ), have been refactored to realize precise and flexible control of production. These studies also offer a promising approach for synthetic pathway refactoring in Actinobacteria. In this review, the great potential of Actinobacteria as a microbial cell factory for biosynthesis of NPs is discussed. To this end, recent progress in metabolic engineering of NP synthetic pathways in Actinobacteria are summarized and strategies and perspectives to rationally and systematically refactor synthetic pathways in Actinobacteria are highlighted. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

LDRD final report : robust analysis of large-scale combinatorial applications.

Energy Technology Data Exchange (ETDEWEB)

Carr, Robert D.; Morrison, Todd (University of Colorado, Denver, CO); Hart, William Eugene; Benavides, Nicolas L. (Santa Clara University, Santa Clara, CA); Greenberg, Harvey J. (University of Colorado, Denver, CO); Watson, Jean-Paul; Phillips, Cynthia Ann

2007-09-01

Discrete models of large, complex systems like national infrastructures and complex logistics frameworks naturally incorporate many modeling uncertainties. Consequently, there is a clear need for optimization techniques that can robustly account for risks associated with modeling uncertainties. This report summarizes the progress of the Late-Start LDRD 'Robust Analysis of Largescale Combinatorial Applications'. This project developed new heuristics for solving robust optimization models, and developed new robust optimization models for describing uncertainty scenarios.

Advances in bio-inspired computing for combinatorial optimization problems

CERN Document Server

Pintea, Camelia-Mihaela

2013-01-01

Advances in Bio-inspired Combinatorial Optimization Problems' illustrates several recent bio-inspired efficient algorithms for solving NP-hard problems.Theoretical bio-inspired concepts and models, in particular for agents, ants and virtual robots are described. Large-scale optimization problems, for example: the Generalized Traveling Salesman Problem and the Railway Traveling Salesman Problem, are solved and their results are discussed.Some of the main concepts and models described in this book are: inner rule to guide ant search - a recent model in ant optimization, heterogeneous sensitive a

Iterative optimization of xylose catabolism in Saccharomyces cerevisiae using combinatorial expression tuning.

Science.gov (United States)

Latimer, Luke N; Dueber, John E

2017-06-01

A common challenge in metabolic engineering is rapidly identifying rate-controlling enzymes in heterologous pathways for subsequent production improvement. We demonstrate a workflow to address this challenge and apply it to improving xylose utilization in Saccharomyces cerevisiae. For eight reactions required for conversion of xylose to ethanol, we screened enzymes for functional expression in S. cerevisiae, followed by a combinatorial expression analysis to achieve pathway flux balancing and identification of limiting enzymatic activities. In the next round of strain engineering, we increased the copy number of these limiting enzymes and again tested the eight-enzyme combinatorial expression library in this new background. This workflow yielded a strain that has a ∼70% increase in biomass yield and ∼240% increase in xylose utilization. Finally, we chromosomally integrated the expression library. This library enriched for strains with multiple integrations of the pathway, which likely were the result of tandem integrations mediated by promoter homology. Biotechnol. Bioeng. 2017;114: 1301-1309. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Synthetic biology for microbial production of lipid-based biofuels.

Science.gov (United States)

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

2015-12-01

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

Synthetic biology for microbial production of lipid-based biofuels

Energy Technology Data Exchange (ETDEWEB)

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

2015-10-23

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

A combinatorial method for the vanishing of the Poisson brackets of an integrable Lotka-Volterra system

International Nuclear Information System (INIS)

Itoh, Yoshiaki

2009-01-01

The combinatorial method is useful to obtain conserved quantities for some nonlinear integrable systems, as an alternative to the Lax representation method. Here we extend the combinatorial method and introduce an elementary geometry to show the vanishing of the Poisson brackets of the Hamiltonian structure for a Lotka-Volterra system of competing species. We associate a set of points on a circle with a set of species of the Lotka-Volterra system, where the dominance relations between points are given by the dominance relations between the species. We associate each term of the conserved quantities with a subset of points on the circle, which simplifies to show the vanishing of the Poisson brackets

Design and Application of Synthetic Receptors for Recognition of Methylated Lysine and Supramolecular Affinity Labeling

Science.gov (United States)

Gober, Isaiah Nathaniel

possible ways for detecting PTMs and may find use in the development of new assays for enzymes that lack robust methods for measuring their activity. The third section explores the development of new small molecule receptors capable of selectively binding hydrophilic guests in water, such as the lower methylation states of lysine. We identified a receptor, A2I, that has improved binding affinity and selectivity for dimethyllysine (Kme2). The receptor was discovered and synthesized by using dynamic combinatorial chemistry (DCC) to redesign a small molecule receptor (A2B ) that preferentially binds trimethyllysine (Kme3). Incorporating a biphenyl monomer with ortho-di-substituted carboxylates into the receptor lead to the formation of a salt bridge interaction with Kme2. These favorable electrostatic and hydrogen bonding interactions produced a receptor with 32-fold tighter binding to Kme2, which is the highest affinity synthetic receptor for Kme2 in the context of a peptide that has been reported. This work provides insight into effective strategies for binding hydrophilic, cationic guests in water and is an encouraging result toward a synthetic receptor that selectively binds Kme2 over other methylation states of lysine. In the final section, a small molecule receptor for Kme3 (A 2B) was redesigned using DCC to incorporate either aromatic or acidic amino acids into the receptor. We proposed that the incorporation of amino acids could introduce additional non-covalent interactions (such as cation-pi, electrostatic, and hydrogen bonding) with a guest bound inside the pocket of the receptor. However, selective non-covalent interactions between the amino acid side chain on the modified receptor and the bound methylated lysine guest could not be achieved. This is most likely due to the conformational flexibility of the amino acid-functionalized receptors. Furthermore, attaching amino acids to the receptor seemed to increase non-specific electrostatic interactions, resulting in

Combinatorial investigation of Pt-Ru-Sn alloys as an anode electrocatalysts for direct alcohol fuel cells

Energy Technology Data Exchange (ETDEWEB)

Chu, Young Hwan [Department of New Energy.Resource Engineering, College of Science and Engineering, Sangji University, 124, Sangjidae-gil, Wonju-si, Gangwon-Do 220-702 (Korea); Shul, Yong Gun [Department of Chemical and Biomolecular Engineering, Yonsei University, 134, Shinchon-Dong, Seodaemun-Gu, Seoul 120-749 (Korea)

2010-10-15

Low-temperature direct alcohol fuel cells fed with different kinds of alcohol (methanol, ethanol and 2-propanol) have been investigated by employing ternary electrocatalysts (Pt-Ru-Sn) as anode catalysts. Combinatorial chemistry has been applied to screen the 66-PtRuSn-anode arrays at the same time to reduce cost, time, and effort when we select the optimum composition of electrocatalysts for DAFCs (Direct Alcohol Fuel Cells). PtRuSn (80:20:0) showed the lowest onset potential for methanol electro-oxidation, PtRuSn (50:0:50) for ethanol, and PtRuSn (20:70:10) for 2-propanol in CV results respectively, and single cell performance test indicated that Ru is more suitable for direct methanol fuel cell system, Sn for direct ethanol fuel cell system, and 2-propanol could be applied as fuel with low platinum composition anode electrocatalyst. The single cell performance results and electrochemical results (CV) were well matched with the combinatorial electrochemical results. As a result, we could verify the availability of combinatorial chemistry by comparing the results of each extreme electrocatalysts compositions as follows: PtRuSn (80:20:0) for methanol, PtRuSn (50:0:50) for ethanol and PtRuSn (20:70:10) for 2-propanol. (author)

Novel modeling of combinatorial miRNA targeting identifies SNP with potential role in bone density.

Directory of Open Access Journals (Sweden)

Claudia Coronnello

Full Text Available MicroRNAs (miRNAs are post-transcriptional regulators that bind to their target mRNAs through base complementarity. Predicting miRNA targets is a challenging task and various studies showed that existing algorithms suffer from high number of false predictions and low to moderate overlap in their predictions. Until recently, very few algorithms considered the dynamic nature of the interactions, including the effect of less specific interactions, the miRNA expression level, and the effect of combinatorial miRNA binding. Addressing these issues can result in a more accurate miRNA:mRNA modeling with many applications, including efficient miRNA-related SNP evaluation. We present a novel thermodynamic model based on the Fermi-Dirac equation that incorporates miRNA expression in the prediction of target occupancy and we show that it improves the performance of two popular single miRNA target finders. Modeling combinatorial miRNA targeting is a natural extension of this model. Two other algorithms show improved prediction efficiency when combinatorial binding models were considered. ComiR (Combinatorial miRNA targeting, a novel algorithm we developed, incorporates the improved predictions of the four target finders into a single probabilistic score using ensemble learning. Combining target scores of multiple miRNAs using ComiR improves predictions over the naïve method for target combination. ComiR scoring scheme can be used for identification of SNPs affecting miRNA binding. As proof of principle, ComiR identified rs17737058 as disruptive to the miR-488-5p:NCOA1 interaction, which we confirmed in vitro. We also found rs17737058 to be significantly associated with decreased bone mineral density (BMD in two independent cohorts indicating that the miR-488-5p/NCOA1 regulatory axis is likely critical in maintaining BMD in women. With increasing availability of comprehensive high-throughput datasets from patients ComiR is expected to become an essential

A complete characterization of the (m,n-cubes and combinatorial applications in imaging, vision and discrete geometry

Directory of Open Access Journals (Sweden)

Daniel Khoshnoudirad

2015-11-01

Full Text Available The aim of this work is to provide a complete characterization of a (m,n-cube. The latter are the pieces of discrete planes appearing in Theoretical Computer Science, Discrete Geometry and Combinatorics. This characterization in three dimensions is the exact equivalent of the preimage for a discrete segment as it has been introduced by McIlroy. Further this characterization, which avoids the redundancies, reduces the combinatorial problem of determining the cardinality of the (m,n-cubes to a new combinatorial problem consisting of determining the volumic regions formed by the crossing of planes. This work can find applications in Imaging, Vision, and pattern recognition for instance.

Combining on-chip synthesis of a focused combinatorial library with computational target prediction reveals imidazopyridine GPCR ligands.

Science.gov (United States)

Reutlinger, Michael; Rodrigues, Tiago; Schneider, Petra; Schneider, Gisbert

2014-01-07

Using the example of the Ugi three-component reaction we report a fast and efficient microfluidic-assisted entry into the imidazopyridine scaffold, where building block prioritization was coupled to a new computational method for predicting ligand-target associations. We identified an innovative GPCR-modulating combinatorial chemotype featuring ligand-efficient adenosine A1/2B and adrenergic α1A/B receptor antagonists. Our results suggest the tight integration of microfluidics-assisted synthesis with computer-based target prediction as a viable approach to rapidly generate bioactivity-focused combinatorial compound libraries with high success rates. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Combinatorial study of WInZnO films deposited by rf magnetron co-sputtering

International Nuclear Information System (INIS)

Oh, Byeong-Yun; Park, Jae-Cheol; Lee, Young-Jun; Cha, Sang-Jun; Kim, Joo-Hyung; Kim, Kwang-Young; Kim, Tae-Won; Heo, Gi-Seok

2011-01-01

The compositional dependence of co-sputtered tungsten indium zinc oxide (WInZnO) film properties was first investigated by means of a combinatorial technique. Indium zinc oxide (IZO) and WO 3 targets were used with different target power. W composition ratio [W/(In+Zn+W)] was varied between 3 and 30 at% and film thickness was reduced as the sample position moved toward WO 3 target. Furthermore, the optical bandgap energy increased gradually, which might be affected by the reduction in film thickness. All the WInZnO films showed an amorphous phase regardless of the W/(In+Zn+W) ratio. As the W/(In+Zn+W) ratio in WInZnO films increased, the carrier concentration was restricted, causing the increase in electrical resistivity. W cations worked as oxygen binders in determining the electronic properties, resulting in suppressing the formation of oxygen vacancies. Consequentially, W metal cations were effectively incorporated into the WInZnO films as a suppressor against the oxygen vacancies and the carrier generation by employing the combinatorial technique. - Graphical abstract: The film thickness and the sheet resistance (R s ) with respect to the sample position of WInZnO films, which is compositionally graded by rf power for each target, are exhibited. Highlights: → The compositional dependence of co-sputtered WInZnO film properties is first investigated. → W cations work as oxygen binders in determining the electronic properties. → All the WInZnO films show an amorphous phase regardless of the W/(In+Zn+W) ratio. → W metal cations are effectively incorporated into the WInZnO films by the combinatorial technique.

Synthetic B-Cell Epitopes Eliciting Cross-Neutralizing Antibodies: Strategies for Future Dengue Vaccine.

Directory of Open Access Journals (Sweden)

Babu Ramanathan

Full Text Available Dengue virus (DENV is a major public health threat worldwide. A key element in protection from dengue fever is the neutralising antibody response. Anti-dengue IgG purified from DENV-2 infected human sera showed reactivity against several peptides when evaluated by ELISA and epitope extraction techniques. A multi-step computational approach predicted six antigenic regions within the E protein of DENV-2 that concur with the 6 epitopes identified by the combined ELISA and epitope extraction approach. The selected peptides representing B-cell epitopes were attached to a known dengue T-helper epitope and evaluated for their vaccine potency. Immunization of mice revealed two novel synthetic vaccine constructs that elicited good humoral immune responses and produced cross-reactive neutralising antibodies against DENV-1, 2 and 3. The findings indicate new directions for epitope mapping and contribute towards the future development of multi-epitope based synthetic peptide vaccine.

Synthetic Approaches to the Lamellarins—A Comprehensive Review

Directory of Open Access Journals (Sweden)

Dennis Imbri

2014-12-01

Full Text Available The present review discusses the known synthetic routes to the lamellarin alkaloids published until 2014. It begins with syntheses of the structurally simpler type-II lamellarins and then focuses on the larger class of the 5,6-saturated and -unsaturated type-I lamellarins. The syntheses are grouped by the strategy employed for the assembly of the central pyrrole ring.

Dissection of combinatorial control by the Met4 transcriptional complex.

Science.gov (United States)

Lee, Traci A; Jorgensen, Paul; Bognar, Andrew L; Peyraud, Caroline; Thomas, Dominique; Tyers, Mike

2010-02-01

Met4 is the transcriptional activator of the sulfur metabolic network in Saccharomyces cerevisiae. Lacking DNA-binding ability, Met4 must interact with proteins called Met4 cofactors to target promoters for transcription. Two types of DNA-binding cofactors (Cbf1 and Met31/Met32) recruit Met4 to promoters and one cofactor (Met28) stabilizes the DNA-bound Met4 complexes. To dissect this combinatorial system, we systematically deleted each category of cofactor(s) and analyzed Met4-activated transcription on a genome-wide scale. We defined a core regulon for Met4, consisting of 45 target genes. Deletion of both Met31 and Met32 eliminated activation of the core regulon, whereas loss of Met28 or Cbf1 interfered with only a subset of targets that map to distinct sectors of the sulfur metabolic network. These transcriptional dependencies roughly correlated with the presence of Cbf1 promoter motifs. Quantitative analysis of in vivo promoter binding properties indicated varying levels of cooperativity and interdependency exists between members of this combinatorial system. Cbf1 was the only cofactor to remain fully bound to target promoters under all conditions, whereas other factors exhibited different degrees of regulated binding in a promoter-specific fashion. Taken together, Met4 cofactors use a variety of mechanisms to allow differential transcription of target genes in response to various cues.

Fragment Linking and Optimization of Inhibitors of the Aspartic Protease Endothiapepsin: Fragment-Based Drug Design Facilitated by Dynamic Combinatorial Chemistry.

Science.gov (United States)

Mondal, Milon; Radeva, Nedyalka; Fanlo-Virgós, Hugo; Otto, Sijbren; Klebe, Gerhard; Hirsch, Anna K H

2016-08-01

Fragment-based drug design (FBDD) affords active compounds for biological targets. While there are numerous reports on FBDD by fragment growing/optimization, fragment linking has rarely been reported. Dynamic combinatorial chemistry (DCC) has become a powerful hit-identification strategy for biological targets. We report the synergistic combination of fragment linking and DCC to identify inhibitors of the aspartic protease endothiapepsin. Based on X-ray crystal structures of endothiapepsin in complex with fragments, we designed a library of bis-acylhydrazones and used DCC to identify potent inhibitors. The most potent inhibitor exhibits an IC50 value of 54 nm, which represents a 240-fold improvement in potency compared to the parent hits. Subsequent X-ray crystallography validated the predicted binding mode, thus demonstrating the efficiency of the combination of fragment linking and DCC as a hit-identification strategy. This approach could be applied to a range of biological targets, and holds the potential to facilitate hit-to-lead optimization. © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Discovery of Antibiotics-derived Polymers for Gene Delivery using Combinatorial Synthesis and Cheminformatics Modeling

Science.gov (United States)

Potta, Thrimoorthy; Zhen, Zhuo; Grandhi, Taraka Sai Pavan; Christensen, Matthew D.; Ramos, James; Breneman, Curt M.; Rege, Kaushal

2014-01-01

We describe the combinatorial synthesis and cheminformatics modeling of aminoglycoside antibiotics-derived polymers for transgene delivery and expression. Fifty-six polymers were synthesized by polymerizing aminoglycosides with diglycidyl ether cross-linkers. Parallel screening resulted in identification of several lead polymers that resulted in high transgene expression levels in cells. The role of polymer physicochemical properties in determining efficacy of transgene expression was investigated using Quantitative Structure-Activity Relationship (QSAR) cheminformatics models based on Support Vector Regression (SVR) and ‘building block’ polymer structures. The QSAR model exhibited high predictive ability, and investigation of descriptors in the model, using molecular visualization and correlation plots, indicated that physicochemical attributes related to both, aminoglycosides and diglycidyl ethers facilitated transgene expression. This work synergistically combines combinatorial synthesis and parallel screening with cheminformatics-based QSAR models for discovery and physicochemical elucidation of effective antibiotics-derived polymers for transgene delivery in medicine and biotechnology. PMID:24331709

An Approach Towards Structure Based Antimicrobial Peptide Design for Use in Development of Transgenic Plants: A Strategy for Plant Disease Management.

Science.gov (United States)

Ilyas, Humaira; Datta, Aritreyee; Bhunia, Anirban

2017-01-01

Antimicrobial peptides (AMPs), also known as host defense peptides (HDPs), are ubiquitous and vital components of innate defense response that present themselves as potential candidates for drug design, and aim to control plant and animal diseases. Though their application for plant disease management has long been studied with natural AMPs, cytotoxicity and stability related shortcomings for the development of transgenic plants limit their usage. Newer technologies like molecular modelling, NMR spectroscopy and combinatorial chemistry allow screening for potent candidates and provide new avenues for the generation of rationally designed synthetic AMPs with multiple biological functions. Such AMPs can be used for the control of plant diseases that lead to huge yield losses of agriculturally important crop plants, via generation of transgenic plants. Such approaches have gained significant attention in the past decade as a consequence of increasing antibiotic resistance amongst plant pathogens, and the shortcomings of existing strategies that include environmental contamination and human/animal health hazards amongst others. This review summarizes the recent trends and approaches used for employing AMPs, emphasizing on designed/modified ones, and their applications toward agriculture and food technology. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Exact combinatorial reliability analysis of dynamic systems with sequence-dependent failures

International Nuclear Information System (INIS)

Xing Liudong; Shrestha, Akhilesh; Dai Yuanshun

2011-01-01

Many real-life fault-tolerant systems are subjected to sequence-dependent failure behavior, in which the order in which the fault events occur is important to the system reliability. Such systems can be modeled by dynamic fault trees (DFT) with priority-AND (pAND) gates. Existing approaches for the reliability analysis of systems subjected to sequence-dependent failures are typically state-space-based, simulation-based or inclusion-exclusion-based methods. Those methods either suffer from the state-space explosion problem or require long computation time especially when results with high degree of accuracy are desired. In this paper, an analytical method based on sequential binary decision diagrams is proposed. The proposed approach can analyze the exact reliability of non-repairable dynamic systems subjected to the sequence-dependent failure behavior. Also, the proposed approach is combinatorial and is applicable for analyzing systems with any arbitrary component time-to-failure distributions. The application and advantages of the proposed approach are illustrated through analysis of several examples. - Highlights: → We analyze the sequence-dependent failure behavior using combinatorial models. → The method has no limitation on the type of time-to-failure distributions. → The method is analytical and based on sequential binary decision diagrams (SBDD). → The method is computationally more efficient than existing methods.

Digitally programmable microfluidic automaton for multiscale combinatorial mixing and sample processing†

Science.gov (United States)

Jensen, Erik C.; Stockton, Amanda M.; Chiesl, Thomas N.; Kim, Jungkyu; Bera, Abhisek; Mathies, Richard A.

2013-01-01

A digitally programmable microfluidic Automaton consisting of a 2-dimensional array of pneumatically actuated microvalves is programmed to perform new multiscale mixing and sample processing operations. Large (µL-scale) volume processing operations are enabled by precise metering of multiple reagents within individual nL-scale valves followed by serial repetitive transfer to programmed locations in the array. A novel process exploiting new combining valve concepts is developed for continuous rapid and complete mixing of reagents in less than 800 ms. Mixing, transfer, storage, and rinsing operations are implemented combinatorially to achieve complex assay automation protocols. The practical utility of this technology is demonstrated by performing automated serial dilution for quantitative analysis as well as the first demonstration of on-chip fluorescent derivatization of biomarker targets (carboxylic acids) for microchip capillary electrophoresis on the Mars Organic Analyzer. A language is developed to describe how unit operations are combined to form a microfluidic program. Finally, this technology is used to develop a novel microfluidic 6-sample processor for combinatorial mixing of large sets (>26 unique combinations) of reagents. The digitally programmable microfluidic Automaton is a versatile programmable sample processor for a wide range of process volumes, for multiple samples, and for different types of analyses. PMID:23172232

Seismic microzoning from synthetic ground motion parameters: Case study, Santiago de Cuba

International Nuclear Information System (INIS)

Alvarez, Leonardo; Vaccari, Franco; Panza, Giuliano F.; Pico, Ramon

2003-08-01

Synthetic seismograms (P - SV and SH waves) have been calculated along 6 profiles in Santiago de Cuba basin, with a cutoff frequency of 5 Hz, by using the hybrid approach (modal summation for a regional (ID) structure plus finite differences for a local (2D) structure embedded in the first). They correspond to a scenario earthquake of M S = 7 that may occur in Oriente fault zone, directly south of the city. As initial data for a seismic microzoning, the characterisation of earthquake effects has been made considering several relative (2D/1D) quantities (PGDR, PGVR, PGAR, DGAR, I A R etc.) and functions representative of the ground motion behaviour in soil (2D) with respect to bedrock (ID). The functions are the response spectra ratio RSR(f), already routinely used in this kind of work, and the elastic energy input ratio E I R(f), defined, for the first time, in this paper. These data, sampled at 105 sites within all the profiles have been classified in two steps, using logical combinatory algorithms: connected sets and compact sets. In the first step, from the original ground motion parameters or functions extracted from the synthetic seismograms, 9 sets have been classified and the partial results show the spatial distribution of the soil behaviour as function of the component of motion. In the second step, the results of the classification of the 9 sets have been used as input for a further classification that shows a spatial distribution of sites with a quasi-homogeneous integral ground motion behaviour. By adding the available geological surface data, a microzoning scheme of Santiago de Cuba basin has been obtained. (author)

Approaches towards the automated interpretation and prediction of electrospray tandem mass spectra of non-peptidic combinatorial compounds.

Science.gov (United States)

Klagkou, Katerina; Pullen, Frank; Harrison, Mark; Organ, Andy; Firth, Alistair; Langley, G John

2003-01-01

Combinatorial chemistry is widely used within the pharmaceutical industry as a means of rapid identification of potential drugs. With the growth of combinatorial libraries, mass spectrometry (MS) became the key analytical technique because of its speed of analysis, sensitivity, accuracy and ability to be coupled with other analytical techniques. In the majority of cases, electrospray mass spectrometry (ES-MS) has become the default ionisation technique. However, due to the absence of fragment ions in the resulting spectra, tandem mass spectrometry (MS/MS) is required to provide structural information for the identification of an unknown analyte. This work discusses the first steps of an investigation into the fragmentation pathways taking place in electrospray tandem mass spectrometry. The ultimate goal for this project is to set general fragmentation rules for non-peptidic, pharmaceutical, combinatorial compounds. As an aid, an artificial intelligence (AI) software package is used to facilitate interpretation of the spectra. This initial study has focused on determining the fragmentation rules for some classes of compound types that fit the remit as outlined above. Based on studies carried out on several combinatorial libraries of these compounds, it was established that different classes of drug molecules follow unique fragmentation pathways. In addition to these general observations, the specific ionisation processes and the fragmentation pathways involved in the electrospray mass spectra of these systems were explored. The ultimate goal will be to incorporate our findings into the computer program and allow identification of an unknown, non-peptidic compound following insertion of its ES-MS/MS spectrum into the AI package. The work herein demonstrates the potential benefit of such an approach in addressing the issue of high-throughput, automated MS/MS data interpretation. Copyright 2003 John Wiley & Sons, Ltd.

Computational design of auxotrophy-dependent microbial biosensors for combinatorial metabolic engineering experiments.

Science.gov (United States)

Tepper, Naama; Shlomi, Tomer

2011-01-21

Combinatorial approaches in metabolic engineering work by generating genetic diversity in a microbial population followed by screening for strains with improved phenotypes. One of the most common goals in this field is the generation of a high rate chemical producing strain. A major hurdle with this approach is that many chemicals do not have easy to recognize attributes, making their screening expensive and time consuming. To address this problem, it was previously suggested to use microbial biosensors to facilitate the detection and quantification of chemicals of interest. Here, we present novel computational methods to: (i) rationally design microbial biosensors for chemicals of interest based on substrate auxotrophy that would enable their high-throughput screening; (ii) predict engineering strategies for coupling the synthesis of a chemical of interest with the production of a proxy metabolite for which high-throughput screening is possible via a designed bio-sensor. The biosensor design method is validated based on known genetic modifications in an array of E. coli strains auxotrophic to various amino-acids. Predicted chemical production rates achievable via the biosensor-based approach are shown to potentially improve upon those predicted by current rational strain design approaches. (A Matlab implementation of the biosensor design method is available via http://www.cs.technion.ac.il/~tomersh/tools).

Library Design-Facilitated High-Throughput Sequencing of Synthetic Peptide Libraries.

Science.gov (United States)

Vinogradov, Alexander A; Gates, Zachary P; Zhang, Chi; Quartararo, Anthony J; Halloran, Kathryn H; Pentelute, Bradley L

2017-11-13

A methodology to achieve high-throughput de novo sequencing of synthetic peptide mixtures is reported. The approach leverages shotgun nanoliquid chromatography coupled with tandem mass spectrometry-based de novo sequencing of library mixtures (up to 2000 peptides) as well as automated data analysis protocols to filter away incorrect assignments, noise, and synthetic side-products. For increasing the confidence in the sequencing results, mass spectrometry-friendly library designs were developed that enabled unambiguous decoding of up to 600 peptide sequences per hour while maintaining greater than 85% sequence identification rates in most cases. The reliability of the reported decoding strategy was additionally confirmed by matching fragmentation spectra for select authentic peptides identified from library sequencing samples. The methods reported here are directly applicable to screening techniques that yield mixtures of active compounds, including particle sorting of one-bead one-compound libraries and affinity enrichment of synthetic library mixtures performed in solution.

Novel Combinatory Approaches to Repair Visual System after Optic Nerve Damage

Science.gov (United States)

2014-09-01

Novel Combinatory Approaches to Repair Visual System After Optic Nerve Damage 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...biological functions such as metabolism, growth, cell cycle, and survival ( Cardone et al., 1998; Diehl, Cheng, Roussel, & Sherr, 1998; Hers, Vincent...of injured adult sensory neurons. The Journal of Neuroscience, 21, 7161–7170. Cardone , M. H., Roy, N., Stennicke, H. R., Salvesen, G. S., Franke, T. F

Combinatorial control of messenger RNAs by Pumilio, Nanos and Brain Tumor Proteins.

Science.gov (United States)

Arvola, René M; Weidmann, Chase A; Tanaka Hall, Traci M; Goldstrohm, Aaron C

2017-11-02

Eukaryotes possess a vast array of RNA-binding proteins (RBPs) that affect mRNAs in diverse ways to control protein expression. Combinatorial regulation of mRNAs by RBPs is emerging as the rule. No example illustrates this as vividly as the partnership of 3 Drosophila RBPs, Pumilio, Nanos and Brain Tumor, which have overlapping functions in development, stem cell maintenance and differentiation, fertility and neurologic processes. Here we synthesize 30 y of research with new insights into their molecular functions and mechanisms of action. First, we provide an overview of the key properties of each RBP. Next, we present a detailed analysis of their collaborative regulatory mechanism using a classic example of the developmental morphogen, hunchback, which is spatially and temporally regulated by the trio during embryogenesis. New biochemical, structural and functional analyses provide insights into RNA recognition, cooperativity, and regulatory mechanisms. We integrate these data into a model of combinatorial RNA binding and regulation of translation and mRNA decay. We then use this information, transcriptome wide analyses and bioinformatics predictions to assess the global impact of Pumilio, Nanos and Brain Tumor on gene regulation. Together, the results support pervasive, dynamic post-transcriptional control.

Effects of synthetic and natural toxicants on livestock.

Science.gov (United States)

Shull, L R; Cheeke, P R

1983-07-01

Synthetic and natural toxicants are constituents of soil, air, water and foodstuffs. Their impact on animal agriculture has resulted from acute and chronic intoxication and residues transferred into meat, dairy and poultry products. Recent advances in analytical chemistry and the sciences associated with toxicology have allowed better assessment of the hazard of toxicants on animals including man. Historically, natural toxicants (phytotoxins, mycotoxins and minerals) that are associated with many common feedstuffs accounted for toxicity episodes of epidemic proportions. Most synthetic chemicals (pesticides, nonpesticidal organic chemicals and drugs) have been introduced in increasing numbers since the 1940's. In the 1960's and '70's, recognition of the need to control their environmental distribution stimulated the introduction of numerous laws and regulations. In the last decade, several problematic synthetic chemicals have been banned, particularly those found to persist in the environment or those confirmed or suspected as carcinogens in humans. At the farm level, the development of various preventative management strategies has decreased the exposure of livestock to natural toxicants. In the future, the impact of natural toxicants on animal agriculture is expected to lessen as their existence, etiology and toxicology are determined. On the other hand, synthetic chemicals will continue to threaten animal health as greater numbers and quantities are released into the environment. These challenges should stimulate a greater involvement of animal scientists in toxicology.

Using Combinatorial Approach to Improve Students' Learning of the Distributive Law and Multiplicative Identities

Science.gov (United States)

Tsai, Yu-Ling; Chang, Ching-Kuch

2009-01-01

This article reports an alternative approach, called the combinatorial model, to learning multiplicative identities, and investigates the effects of implementing results for this alternative approach. Based on realistic mathematics education theory, the new instructional materials or modules of the new approach were developed by the authors. From…

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.

Nonlinear dimensionality reduction methods for synthetic biology biobricks' visualization.

Science.gov (United States)

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

2017-01-19

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

Theory of site-specific interactions of the combinatorial transcription factors with DNA

International Nuclear Information System (INIS)

Murugan, R

2010-01-01

We derive a functional relationship between the mean first passage time associated with the concurrent binding of multiple transcription factors (TFs) at their respective combinatorial cis-regulatory module sites (CRMs) and the number n of TFs involved in the regulation of the initiation of transcription of a gene of interest. Our results suggest that the overall search time τ s that is required by the n TFs to locate their CRMs which are all located on the same DNA chain scales with n as τ s ∼n α where α ∼ (2/5). When the jump size k that is associated with the dynamics of all the n TFs along DNA is higher than that of the critical jump size k c that scales with the size of DNA N as k c ∼ N 2/3 , we observe a similar power law scaling relationship and also the exponent α. When k c , α shows a strong dependence on both n and k. Apparently there is a critical number of combinatorial TFs n c ∼ 20 that is required to efficiently regulate the initiation of transcription of a given gene below which (2/5) 1. These results seem to be independent of the initial distances between the TFs and their corresponding CRMs and also suggest that the maximum number of TFs involved in a given combinatorial regulation of the initiation of transcription of a gene of interest seems to be restricted by the degree of condensation of the genomic DNA. The optimum number m opt of roadblock protein molecules per genome at which the search time associated with these n TFs to locate their binding sites is a minimum seems to scale as m opt ∼Ln α/2 where L is the sliding length of TFs whose maximum value seems to be such that L ≤ 10 4 bps for the E. coli bacterial genome.

Metal-ion induced amplification of three receptors from dynamic combinatorial libraries of peptide-hydrazones

NARCIS (Netherlands)

Roberts, Sarah L.; Furlan, Ricardo L.E.; Otto, Sijbren; Sanders, Jeremy K.M.

2003-01-01

Three building blocks of general structure (MeO)2CH–aromatic linker–Pro–amino acid–NHNH2 have been prepared and tested in acid-catalysed dynamic combinatorial libraries. Exposure of these libraries to LiI and NaI led to the amplification of three macrocyclic pseudopeptide receptors. The receptors

Combinatorial enzyme technology: Conversion of pectin to oligo species and its effect on microbial growth

Science.gov (United States)

Plant cell wall polysaccharides, which consist of polymeric backbones with various types of substitution, were studied using the concept of combinatorial enzyme technology for conversion of agricultural fibers to functional products. Using citrus pectin as the starting substrate, an active oligo spe...

Design of diversity and focused combinatorial libraries in drug discovery.

Science.gov (United States)

Young, S Stanley; Ge, Nanxiang

2004-05-01

Using well-characterized chemical reactions and readily available monomers, chemists are able to create sets of compounds, termed libraries, which are useful in drug discovery processes. The design of combinatorial chemical libraries can be complex and there has been much information recently published offering suggestions on how the design process can be carried out. This review focuses on literature with the goal of organizing current thinking. At this point in time, it is clear that benchmarking of current suggested methods is required as opposed to further new methods.

Novel green synthetic strategy to prepare ZnO nanocrystals using rambutan (Nephelium lappaceum L.) peel extract and its antibacterial applications.

Science.gov (United States)

Yuvakkumar, R; Suresh, J; Nathanael, A Joseph; Sundrarajan, M; Hong, S I

2014-08-01

In the present investigation, we report a sustainable novel green synthetic strategy to synthesis zinc oxide nanocrystals. This is the first report on sustainable biosynthesis of zinc oxide nanocrystals employing Nephelium lappaceum L., peel extract as a natural ligation agent. Green synthesis of zinc oxide nanocrystals was carried out via zinc-ellagate complex formation using rambutan peel wastes. The successful formation of zinc oxide nanocrystals was confirmed employing standard characterisation studies. A possible mechanism for the formation of ZnO nanocrystals with rambutan peel extract was also proposed. The prepared ZnO nanocrystals were coated on the cotton fabric and their antibacterial activity were analyzed. ZnO nanocrystals coated cotton showed good antibacterial activity towards Escherichia coli (E. coli), gram negative bacteria and Staphylococcus aureus (S. aureus), gram positive bacteria. Copyright © 2014 Elsevier B.V. All rights reserved.

Combinatorial formulas for Kazhdan-Lusztig polynomials with respect to W-graph ideals

OpenAIRE

Wang, Qi

2017-01-01

In \\cite{y1} Yin generalized the definition of $W$-graph ideal $E_J$ in weighted Coxeter groups and introduced the weighted Kazhdan-Lusztig polynomials $ \\left \\{ P_{x,y} \\mid x,y\\in E_J\\right \\}$, where $J$ is a subset of simple generators $S$. In this paper, we study the combinatorial formulas for those polynomials, which extend the results of Deodhar \\cite{v3} and Tagawa \\cite{h1}.

Principles of Linguistic Composition Below and Beyond the Clause—Elements of a semantic combinatorial system

DEFF Research Database (Denmark)

Bundgaard, Peer

2006-01-01

beyond the scope of the clause. To this end it exposes two major principles of semantic combination that are active through all levels of linguistic composition: viz. frame-schematic structure and narrative structure. These principles are considered as being components of a semantic combinatorial system...

A synthetic combinatorial strategy for developing a-conotoxin analogs as potent a7 nicotinic acetylcholine receptor antagonists

DEFF Research Database (Denmark)

Armishaw, Christopher J; Singh, Narender; Medina-Franco, Jose L

2010-01-01

alpha-Conotoxins are peptide neurotoxins isolated from venomous cone snails that display exquisite selectivity for different subtypes of nicotinic acetylcholine receptors (nAChR). They are valuable research tools that have profound implications in the discovery of new drugs for a myriad of neurop......alpha-Conotoxins are peptide neurotoxins isolated from venomous cone snails that display exquisite selectivity for different subtypes of nicotinic acetylcholine receptors (nAChR). They are valuable research tools that have profound implications in the discovery of new drugs for a myriad...

Programmed coherent coupling in a synthetic DNA-based excitonic circuit

Science.gov (United States)

Boulais, Étienne; Sawaya, Nicolas P. D.; Veneziano, Rémi; Andreoni, Alessio; Banal, James L.; Kondo, Toru; Mandal, Sarthak; Lin, Su; Schlau-Cohen, Gabriela S.; Woodbury, Neal W.; Yan, Hao; Aspuru-Guzik, Alán; Bathe, Mark

2018-02-01

Natural light-harvesting systems spatially organize densely packed chromophore aggregates using rigid protein scaffolds to achieve highly efficient, directed energy transfer. Here, we report a synthetic strategy using rigid DNA scaffolds to similarly program the spatial organization of densely packed, discrete clusters of cyanine dye aggregates with tunable absorption spectra and strongly coupled exciton dynamics present in natural light-harvesting systems. We first characterize the range of dye-aggregate sizes that can be templated spatially by A-tracts of B-form DNA while retaining coherent energy transfer. We then use structure-based modelling and quantum dynamics to guide the rational design of higher-order synthetic circuits consisting of multiple discrete dye aggregates within a DX-tile. These programmed circuits exhibit excitonic transport properties with prominent circular dichroism, superradiance, and fast delocalized exciton transfer, consistent with our quantum dynamics predictions. This bottom-up strategy offers a versatile approach to the rational design of strongly coupled excitonic circuits using spatially organized dye aggregates for use in coherent nanoscale energy transport, artificial light-harvesting, and nanophotonics.

What Diagrams Argue in Late Imperial Chinese Combinatorial Texts.

Science.gov (United States)

Bréard, Andrea

2015-01-01

Attitudes towards diagrammatic reasoning and visualization in mathematics were seldom spelled out in texts from pre-modern China, although illustrations figure prominently in mathematical literature since the eleventh century. Taking the sums of finite series and their combinatorial interpretation as a case study, this article investigates the epistemological function of illustrations from the eleventh to the nineteenth century that encode either the mathematical objects themselves or represent their related algorithms. It particularly focuses on the two illustrations given in Wang Lai's (1768-1813) Mathematical Principles of Sequential Combinations, arguing that they reflect a specific mode of nineteenth-century mathematical argumentative practice and served as a heuristic model for later authors.

Fabrication and characterization of thin-film phosphor combinatorial libraries

Science.gov (United States)

Mordkovich, V. Z.; Jin, Zhengwu; Yamada, Y.; Fukumura, T.; Kawasaki, M.; Koinuma, H.

2002-05-01

The laser molecular beam epitaxy method was employed to fabricate thin-film combinatorial libraries of ZnO-based phosphors on different substrates. Fabrication of both pixel libraries, on the example of Fe-doped ZnO, and spread libraries, on the example of Eu-doped ZnO, has been demonstrated. Screening of the Fe-doped ZnO libraries led to the discovery of weak green cathodoluminescence with the maximum efficiency at the Fe content of 0.58 mol %. Screening of the Eu-doped ZnO libraries led to the discovery of unusual reddish-violet cathodoluminescence which is observed in a broad range of Eu concentration. No photoluminescence was registered in either system.

Frequency Stability Enhancement for Low Inertia Systems using Synthetic Inertia of Wind Power

DEFF Research Database (Denmark)

Nguyen, Ha Thi; Yang, Guangya; Nielsen, Arne Hejde

2017-01-01

stability, this paper proposes supplementary control methods to implement synthetic inertia for doubly-fed induction generator (DFIG) based wind energy system during frequency excursions. Different control strategies and activation schemes are analyzed and implemented on the Western Danish renewable......-based system using-real time digital simulator (RTDS) to propose the best one for the synthetic inertia controller. From the comparative simulation results, it can be concluded that the method using a combination of both the frequency deviation and derivative as input signals, and the under-frequency trigger...

Freedom and Responsibility in Synthetic Genomics: The Synthetic Yeast Project

OpenAIRE

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

2015-01-01

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

Combinatorial metabolic engineering of industrial Gluconobacter oxydans DSM2343 for boosting 5-keto-D-gluconic acid accumulation.

Science.gov (United States)

Yuan, Jianfeng; Wu, Mianbin; Lin, Jianping; Yang, Lirong

2016-05-17

L-(+)-tartaric acid (L-TA) is an important organic acid, which is produced from the cream of tartar or stereospecific hydrolysis of the cis-epoxysuccinate. The former method is limited by the availability of raw material and the latter is dependent on the petrochemical material. Thus, new processes for the economical preparation of L-TA from carbohydrate or renewable resource would be much more attractive. Production of 5-keto-D-gluconate (5-KGA) from glucose by Gluconobacter oxydans is the first step to produce L-TA. The aim of this work is to enhance 5-KGA accumulation using combinatorial metabolic engineering strategies in G. oxydans. The sldAB gene, encoding sorbitol dehydrogenase, was overexpressed in an industrial strain G. oxydans ZJU2 under a carefully selected promoter, P0169. To enhance the efficiency of the oxidation by sldAB, the coenzyme pyrroloquinoline quinone (PQQ) and respiratory chain were engineered. Besides, the role in sldAB overexpression, coenzyme and respiratory chain engineering and their subsequent effects on 5-KGA production were investigated. An efficient, stable recombinant strain was constructed, whereas the 5-KGA production could be enhanced. By self-overexpressing the sldAB gene in G. oxydans ZJU2 under the constitutive promoter P0169, the resulting strain, G. oxydans ZJU3, produced 122.48 ± 0.41 g/L of 5-KGA. Furthermore, through the coenzyme and respiratory chain engineering, the titer and productivity of 5-KGA reached 144.52 ± 2.94 g/L and 2.26 g/(L · h), respectively, in a 15 L fermenter. It could be further improved the 5-KGA titer by 12.10 % through the fed-batch fermentation under the pH shift and dissolved oxygen tension (DOT) control condition, obtained 162 ± 2.12 g/L with the productivity of 2.53 g/(L · h) within 64 h. The 5-KGA production could be significantly enhanced with the combinatorial metabolic engineering strategy in Gluconobacter strain, including sldAB overexpression, coenzyme

Genome-scale regression analysis reveals a linear relationship for promoters and enhancers after combinatorial drug treatment

KAUST Repository

Rapakoulia, Trisevgeni

2017-08-09

Motivation: Drug combination therapy for treatment of cancers and other multifactorial diseases has the potential of increasing the therapeutic effect, while reducing the likelihood of drug resistance. In order to reduce time and cost spent in comprehensive screens, methods are needed which can model additive effects of possible drug combinations. Results: We here show that the transcriptional response to combinatorial drug treatment at promoters, as measured by single molecule CAGE technology, is accurately described by a linear combination of the responses of the individual drugs at a genome wide scale. We also find that the same linear relationship holds for transcription at enhancer elements. We conclude that the described approach is promising for eliciting the transcriptional response to multidrug treatment at promoters and enhancers in an unbiased genome wide way, which may minimize the need for exhaustive combinatorial screens.

Zoledronic acid produces combinatory anti-tumor effects with cisplatin on mesothelioma by increasing p53 expression levels.

Directory of Open Access Journals (Sweden)

Shinya Okamoto

Full Text Available We examined anti-tumor effects of zoledronic acid (ZOL, one of the bisphosphonates agents clinically used for preventing loss of bone mass, on human mesothelioma cells bearing the wild-type p53 gene. ZOL-treated cells showed activation of caspase-3/7, -8 and -9, and increased sub-G1 phase fractions. A combinatory use of ZOL and cisplatin (CDDP, one of the first-line anti-cancer agents for mesothelioma, synergistically or additively produced the cytotoxicity on mesothelioma cells. Moreover, the combination achieved greater anti-tumor effects on mesothelioma developed in the pleural cavity than administration of either ZOL or CDDP alone. ZOL-treated cells as well as CDDP-treated cells induced p53 phosphorylation at Ser 15, a marker of p53 activation, and up-regulated p53 protein expression levels. Down-regulation of p53 levels with siRNA however did not influence the ZOL-mediated cytotoxicity but negated the combinatory effects by ZOL and CDDP. In addition, ZOL treatments augmented cytotoxicity of adenoviruses expressing the p53 gene on mesothelioma. These data demonstrated that ZOL-mediated augmentation of p53, which was not linked with ZOL-induced cytotoxicity, played a role in the combinatory effects with a p53 up-regulating agent, and suggests a possible clinical use of ZOL to mesothelioma with anti-cancer agents.

A Synthetic-Biology-Inspired Therapeutic Strategy for Targeting and Treating Hepatogenous Diabetes.

Science.gov (United States)

Xue, Shuai; Yin, Jianli; Shao, Jiawei; Yu, Yuanhuan; Yang, Linfeng; Wang, Yidan; Xie, Mingqi; Fussenegger, Martin; Ye, Haifeng

2017-02-01

Hepatogenous diabetes is a complex disease that is typified by the simultaneous presence of type 2 diabetes and many forms of liver disease. The chief pathogenic determinant in this pathophysiological network is insulin resistance (IR), an asymptomatic disease state in which impaired insulin signaling in target tissues initiates a variety of organ dysfunctions. However, pharmacotherapies targeting IR remain limited and are generally inapplicable for liver disease patients. Oleanolic acid (OA) is a plant-derived triterpenoid that is frequently used in Chinese medicine as a safe but slow-acting treatment in many liver disorders. Here, we utilized the congruent pharmacological activities of OA and glucagon-like-peptide 1 (GLP-1) in relieving IR and improving liver and pancreas functions and used a synthetic-biology-inspired design principle to engineer a therapeutic gene circuit that enables a concerted action of both drugs. In particular, OA-triggered short human GLP-1 (shGLP-1) expression in hepatogenous diabetic mice rapidly and simultaneously attenuated many disease-specific metabolic failures, whereas OA or shGLP-1 monotherapy failed to achieve corresponding therapeutic effects. Collectively, this work shows that rationally engineered synthetic gene circuits are capable of treating multifactorial diseases in a synergistic manner by multiplexing the targeting efficacies of single therapeutics. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

“Click” Synthesis of Dextran Macrostructures for Combinatorial-Designed Self-Assembled Nanoparticles Encapsulating Diverse Anticancer Therapeutics

Science.gov (United States)

Abeylath, Sampath C.; Amiji, Mansoor

2011-01-01

With the non-specific toxicity of anticancer drugs to healthy tissues upon systemic administration, formulations capable of enhanced selectivity in delivery to the tumor mass and cells are highly desirable. Based on the diversity of the drug payloads, we have investigated a combinatorial-designed strategy where the nano-sized formulations are tailored based on the physicochemical properties of the drug and the delivery needs. Individually functionalized C2 to C12 lipid-, thiol-, and poly(ethylene glycol) (PEG)-modified dextran derivatives were synthesized via “click” chemistry from O-pentynyl dextran and relevant azides. These functionalized dextrans in combination with anticancer drugs form nanoparticles by self-assembling in aqueous medium having PEG surface functionalization and intermolecular disulfide bonds. Using anticancer drugs with logP values ranging from −0.5 to 3.0, the optimized nanoparticles formulations were evaluated for preliminary cellular delivery and cytotoxic effects in SKOV3 human ovarian adenocarcinoma cells. The results show that with the appropriate selection of lipid-modified dextran, one can effectively tailor the self-assembled nano-formulation for intended therapeutic payload. PMID:21978947

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

Directory of Open Access Journals (Sweden)

Anand Kumar Tripathi

2015-03-01

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

Efficiency Intra-Cluster Device-to-Device Relay Selection for Multicast Services Based on Combinatorial Auction

Directory of Open Access Journals (Sweden)

Yong Zhang

2015-12-01

Full Text Available In Long Term Evolution-Advanced (LTE-A networks, Device-to-device (D2D communications can be utilized to enhance the performance of multicast services by leveraging D2D relays to serve nodes with worse channel conditions within a cluster. For traditional D2D relay schemes, D2D links with poor channel condition may be the bottleneck of system sum data rate. In this paper, to optimize the throughput of D2D communications, we introduce an iterative combinatorial auction algorithm for efficient D2D relay selection. In combinatorial auctions, the User Equipments (UEs that fails to correctly receive multicast data from eNodeB (eNB are viewed as bidders that compete for D2D relays, while the eNB is treated as the auctioneer. We also give properties of convergency and low-complexity and present numerical simulations to verify the efficiency of the proposed algorithm.

A combinatorial approach of inclusion complexation and dendrimer synthesization for effective targeting EGFR-TK.

Science.gov (United States)

Shende, Pravin; Patil, Sampada; Gaud, R S

2017-07-01

The aim of the present study was to use a combinatorial approach of inclusion complexation and dendrimer synthesization of gefitinib using solvent-free technique for targeting EGFR-TK to treat Non-Small-Cell Lung Cancer (NSCLC). The inclusion complex of gefitinib with β-cyclodextrin was prepared by trituration method. This complex encapsulated G4 PAMAM dendrimers were synthesized by Michael addition and amidation reactions using green chemistry and then PEGylated by conjugation reaction. FTIR and DSC confirmed the formation of inclusion complex of gefitinib and β-cyclodextrin and PEGylation of G4 PAMAM dendrimers. Gefitinib showed higher solubility, encapsulation efficiency and controlled release profile from PEGylated dendrimers compared to inclusion complex. The PEGylated dendrimers of inclusion complex of gefitinib were found to reduce hemolytic toxicity and lesser GI 50 value on Human lung cancer cell line A-549 by effective targeting EGFR-TK. A combinatorial approach of inclusion complexation and dendrimer synthesization is one of the alternative advanced approaches to treat NSCLC. Copyright © 2017 Elsevier B.V. All rights reserved.

Advanced research and development for plasma processing of polymers with combinatorial plasma-process analyzer

International Nuclear Information System (INIS)

Setsuhara, Yuichi; Cho, Ken; Takenaka, Kosuke; Shiratani, Masaharu; Sekine, Makoto; Hori, Masaru

2010-01-01

A plasma-process analyzer has been developed on the basis of combinatorial method, in which process examinations with continuous variations of plasma-process conditions can be carried out on a substrate holder with an inclined distribution of process parameters. Combinatorial plasma-process analyses have been demonstrated for examinations of plasma-polymer interactions in terms of etching characteristics and surface morphologies in order to show feasibility and effectiveness of the methodology as advanced research and development for next-generation plasma nano processes. The etching properties and surface morphologies have been investigated for polyethylene terephthalate (PET) films exposed to argon-oxygen mixture plasmas. The etching depth data obtained from three independent batches of the experiments showed universal and almost linear dependence with increasing product of (ion saturation current) x (exposure time); i.e. ion dose. Surface roughness of the polymer slightly increased with increasing ion dose, while the mean spacing after plasma exposure was found to decrease monotonically with increasing ion dose but was saturated at the level of approximately 250 nm.

An improved fuzzy synthetic condition assessment of a wind turbine generator system

DEFF Research Database (Denmark)

Li, H.; Hu, Y. G.; Yang, Chao

2013-01-01

This paper presents an improved fuzzy synthetic model that is based on a real-time condition assessment method of a grid-connected wind turbine generator system (WTGS) to improve the operational reliability and optimize the maintenance strategy. First, a condition assessment framework is proposed...... by analyzing the monitoring data of the WTGS. An improved fuzzy synthetic condition assessment method is then proposed that utilizes the concepts of deterioration degree, dynamic limited values and variable weight calculations of the assessment indices. Finally, by using on-line monitoring data of an actual...... 850 kW WTGS, real-time condition assessments are performed that utilize the proposed fuzzy synthetic method; the model’s effectiveness is also compared to a traditional fuzzy assessment method in which constant limited values and constant weights are adopted. The results show that the condition...

Combinatorial interpretations of binomial coefficient analogues related to Lucas sequences

OpenAIRE

Sagan, Bruce; Savage, Carla

2009-01-01

Let s and t be variables. Define polynomials {n} in s, t by {0}=0, {1}=1, and {n}=s{n-1}+t{n-2} for n >= 2. If s, t are integers then the corresponding sequence of integers is called a Lucas sequence. Define an analogue of the binomial coefficients by C{n,k}={n}!/({k}!{n-k}!) where {n}!={1}{2}...{n}. It is easy to see that C{n,k} is a polynomial in s and t. The purpose of this note is to give two combinatorial interpretations for this polynomial in terms of statistics on integer partitions in...

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

Science.gov (United States)

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

2015-08-01

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

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

Science.gov (United States)

Brown, Adam J; James, David C

2016-01-01

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

Norbadione A: synthetic approach and cesium complexation studies

International Nuclear Information System (INIS)

Desage - El Murr, M.

2003-10-01

This work was dedicated to the study of the synthesis and complexation studies of norbadione A: a pigment originating from a mushroom. A synthetic approach, based on a double Suzuki-Miyaura coupling, was developed. This strategy was applied with high yields to the synthesis of various norbadione A analogues, as well as to the synthesis of simple pulvinic acids. Access to functionalized precursors of the molecule was also studied and the final coupling remains to be done. Besides, a speciation study based on electro-spray ionization mass spectrometry was conducted with norbadione A and one of the analogues. This study allowed the assessment of the cesium complexation abilities of each molecule. Structural data was also obtained and complexation constants were calculated. Finally, norbadione A and various synthetic products have been tested via high-throughput screening methods and strong antioxidant properties were observed. Other biological results are also reported. (author)

SYNTHETIC STRATEGY FOR THE PREPARATION OF BIOACTIVE GALACTOGLYCEROLIPIDS

Directory of Open Access Journals (Sweden)

Emiliano Manzo

2011-12-01

Full Text Available The current communication represents an extended abstract of the presentation delivered on the joint Moldo-Italian seminar “New frontiers in natural product chemistry”, held in the Institute of Chemistry, Academy of Sciences of Moldova on 30 September. A simple and efficient strategy for the synthesis of galactoglycerolipids is provided.

Combinatorial Drug Screening Identifies Ewing Sarcoma-specific Sensitivities

DEFF Research Database (Denmark)

Radic-Sarikas, Branka; Tsafou, Kalliopi P; Emdal, Kristina B.

2017-01-01

Improvements in survival for Ewing sarcoma pediatric and adolescent patients have been modest over the past 20 years. Combinations of anticancer agents endure as an option to overcome resistance to single treatments caused by compensatory pathways. Moreover, combinations are thought to lessen any...... associated adverse side effects through reduced dosing, which is particularly important in childhood tumors. Using a parallel phenotypic combinatorial screening approach of cells derived from three pediatric tumor types, we identified Ewing sarcoma-specific interactions of a diverse set of targeted agents...... including approved drugs. We were able to retrieve highly synergistic drug combinations specific for Ewing sarcoma and identified signaling processes important for Ewing sarcoma cell proliferation determined by EWS-FLI1 We generated a molecular target profile of PKC412, a multikinase inhibitor with strong...

Synthetic Adhesive Attachment Discs based on Spider Pyriform Silk Architecture

Science.gov (United States)

Jain, Dharamdeep; Sahni, Vasav; Dhinojwala, Ali

2014-03-01

Among the variety of silks produced by spiders, pyriform silk is used in conjunction with the dragline silk to attach webs to different surfaces. Cob weaver spiders employ different architectural patterns to utilize the pyriform silk and form attachment joints with each pattern having a characteristic adhesive performance. The staple pin architecture is a one of the strongest attachment designs employed by spiders to attach their webs. Here we use a synthetic approach to create the a similar patterned architecture attachment discs on aluminum substrate using thermoplastic polyurethane. Measurable pull off forces are generated when the synthetic discs are peeled off a surface. This innovative adhesive strategy can be a source of design in various biomedical applications. Financial Support from National Science Foundation.

The Classicist and the Frequentist Approach to Probability within a "TinkerPlots2" Combinatorial Problem

Science.gov (United States)

Prodromou, Theodosia

2012-01-01

This article seeks to address a pedagogical theory of introducing the classicist and the frequentist approach to probability, by investigating important elements in 9th grade students' learning process while working with a "TinkerPlots2" combinatorial problem. Results from this research study indicate that, after the students had seen…

Epigenetic-based combinatorial resveratrol and pterostilbene alters DNA damage response by affecting SIRT1 and DNMT enzyme expression, including SIRT1-dependent γ-H2AX and telomerase regulation in triple-negative breast cancer

International Nuclear Information System (INIS)

Kala, Rishabh; Shah, Harsh N.; Martin, Samantha L.; Tollefsbol, Trygve O.

2015-01-01

, the effects of this combination treatment was also explored on DNA methyltransferases (DNMTs) expression. Interestingly, the compounds resulted in a significant down-regulation of DNMT enzymes with no significant effects on DNMT enzyme expression in MCF10A control cells. Collectively, these results provide new insights into the epigenetic mechanisms of a novel combinatorial nutrient control strategy that exhibits synergy and may contribute to future recalcitrant TNBC prevention and/or therapy. The online version of this article (doi:10.1186/s12885-015-1693-z) contains supplementary material, which is available to authorized users

CCLab--a multi-objective genetic algorithm based combinatorial library design software and an application for histone deacetylase inhibitor design.

Science.gov (United States)

Fang, Guanghua; Xue, Mengzhu; Su, Mingbo; Hu, Dingyu; Li, Yanlian; Xiong, Bing; Ma, Lanping; Meng, Tao; Chen, Yuelei; Li, Jingya; Li, Jia; Shen, Jingkang

2012-07-15

The introduction of the multi-objective optimization has dramatically changed the virtual combinatorial library design, which can consider many objectives simultaneously, such as synthesis cost and drug-likeness, thus may increase positive rates of biological active compounds. Here we described a software called CCLab (Combinatorial Chemistry Laboratory) for combinatorial library design based on the multi-objective genetic algorithm. Tests of the convergence ability and the ratio to re-take the building blocks in the reference library were conducted to assess the software in silico, and then it was applied to a real case of designing a 5×6 HDAC inhibitor library. Sixteen compounds in the resulted library were synthesized, and the histone deactetylase (HDAC) enzymatic assays proved that 14 compounds showed inhibitory ratios more than 50% against tested 3 HDAC enzymes at concentration of 20 μg/mL, with IC(50) values of 3 compounds comparable to SAHA. These results demonstrated that the CCLab software could enhance the hit rates of the designed library and would be beneficial for medicinal chemists to design focused library in drug development (the software can be downloaded at: http://202.127.30.184:8080/drugdesign.html). Copyright © 2012 Elsevier Ltd. All rights reserved.

Combinatorial Dansyl Library and its Applications to pH-Responsive Probes.

Science.gov (United States)

Hong, Seong Cheol; Murale, Dhiraj P; Lee, Jun-Seok

2016-01-01

Herein, we report the first 48-membered, dansyl-based, combinatorial fluorescent library. From the electronic and structural properties of the probes, we analyzed their optical properties and chemical yields, with an average of 49 %. The molecules were examined for their pH responses, and DS-2 and DS-45 showed blue-shifts, whereas DS-7 and DS-40 showed red-shifts in wavelength with increasing pH. Finally, cell permeability was investigated by treating SNU-2292 cells. Our results demonstrate the potential application of this library in biosensors, bio-imaging and pH indicators.

Radical scavenging potentials of single and combinatorial herbal formulations in vitro

Directory of Open Access Journals (Sweden)

Okey A. Ojiako

2016-04-01

Full Text Available Reactive oxygen and nitrogen species (RONS are involved in deleterious/beneficial biological processes. The present study sought to investigate the capacity of single and combinatorial herbal formulations of Acanthus montanus, Emilia coccinea, Hibiscus rosasinensis, and Asystasia gangetica to act as superoxide radicals (SOR, hydrogen peroxide (HP, nitric oxide radical (NOR, hydroxyl radical (HR, and 2,2-diphenyl-1-picrylhydrazyl (DPPH radical antagonists using in vitro models. The herbal extracts were single herbal formulations (SHfs, double herbal formulations (DHfs, triple herbal formulations (THfs, and a quadruple herbal formulation (QHf. The phytochemical composition and radical scavenging capacity index (SCI of the herbal formulations were measured using standard methods. The flavonoids were the most abundant phytochemicals present in the herbal extracts. The SCI50 defined the concentration (μg/mL of herbal formulation required to scavenge 50% of the investigated radicals. The SHfs, DHfs, THfs, and QHf SCI50 against the radicals followed the order HR > SOR > DPPH radical > HP > NOR. Although the various herbal formulations exhibited ambivalent antioxidant activities in terms of their radical scavenging capabilities, a broad survey of the results of the present study showed that combinatorial herbal formulations (DHfs, THfs, and QHf appeared to exhibit lower radical scavenging capacities than those of the SHfs in vitro.

Identification and Interrogation of Combinatorial Histone Modifications

Directory of Open Access Journals (Sweden)

Kelly R Karch

2013-12-01

Full Text Available Histone proteins are dynamically modified to mediate a variety of cellular processes including gene transcription, DNA damage repair, and apoptosis. Regulation of these processes occurs through the recruitment of non-histone proteins to chromatin by specific combinations of histone post-translational modifications (PTMs. Mass spectrometry has emerged as an essential tool to discover and quantify histone PTMs both within and between samples in an unbiased manner. Developments in mass spectrometry that allow for characterization of large histone peptides or intact protein has made it possible to determine which modifications occur simultaneously on a single histone polypeptide. A variety of techniques from biochemistry, biophysics, and chemical biology have been employed to determine the biological relevance of discovered combinatorial codes. This review first describes advancements in the field of mass spectrometry that have facilitated histone PTM analysis and then covers notable approaches to probe the biological relevance of these modifications in their nucleosomal context.

Synthetic environments

Science.gov (United States)

Lukes, George E.; Cain, Joel M.

1996-02-01

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

Phthalocyanine-loaded graphene nanoplatform for imaging-guided combinatorial phototherapy

Directory of Open Access Journals (Sweden)

Taratula O

2015-03-01

Full Text Available Olena Taratula,1 Mehulkumar Patel,2 Canan Schumann,1 Michael A Naleway,1 Addison J Pang,1 Huixin He,2 Oleh Taratula1 1Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Portland, OR, USA; 2Department of Chemistry, Rutgers University-Newark, Newark, NJ, USA Abstract: We report a novel cancer-targeted nanomedicine platform for imaging and prospect for future treatment of unresected ovarian cancer tumors by intraoperative multimodal phototherapy. To develop the required theranostic system, novel low-oxygen graphene nanosheets were chemically modified with polypropylenimine dendrimers loaded with phthalocyanine (Pc as a photosensitizer. Such a molecular design prevents fluorescence quenching of the Pc by graphene nanosheets, providing the possibility of fluorescence imaging. Furthermore, the developed nanoplatform was conjugated with poly(ethylene glycol, to improve biocompatibility, and with luteinizing hormone-releasing hormone (LHRH peptide, for tumor-targeted delivery. Notably, a low-power near-infrared (NIR irradiation of single wavelength was used for both heat generation by the graphene nanosheets (photothermal therapy [PTT] and for reactive oxygen species (ROS-production by Pc (photodynamic therapy [PDT]. The combinatorial phototherapy resulted in an enhanced destruction of ovarian cancer cells, with a killing efficacy of 90%–95% at low Pc and low-oxygen graphene dosages, presumably conferring cytotoxicity to the synergistic effects of generated ROS and mild hyperthermia. An animal study confirmed that Pc loaded into the nanoplatform can be employed as a NIR fluorescence agent for imaging-guided drug delivery. Hence, the newly developed Pc-graphene nanoplatform has the significant potential as an effective NIR theranostic probe for imaging and combinatorial phototherapy. Keywords: graphene nanosheets, phthalocyanine, photothermal therapy, photodynamic therapy, theranostic 

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.

Plant synthetic biology: a new platform for industrial biotechnology.

Science.gov (United States)

Fesenko, Elena; Edwards, Robert

2014-05-01

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

Combinatorial Screening for Transgenic Yeasts with High Cellulase Activities in Combination with a Tunable Expression System.

Directory of Open Access Journals (Sweden)

Yoichiro Ito

Full Text Available Combinatorial screening used together with a broad library of gene expression cassettes is expected to produce a powerful tool for the optimization of the simultaneous expression of multiple enzymes. Recently, we proposed a highly tunable protein expression system that utilized multiple genome-integrated target genes to fine-tune enzyme expression in yeast cells. This tunable system included a library of expression cassettes each composed of three gene-expression control elements that in different combinations produced a wide range of protein expression levels. In this study, four gene expression cassettes with graded protein expression levels were applied to the expression of three cellulases: cellobiohydrolase 1, cellobiohydrolase 2, and endoglucanase 2. After combinatorial screening for transgenic yeasts simultaneously secreting these three cellulases, we obtained strains with higher cellulase expressions than a strain harboring three cellulase-expression constructs within one high-performance gene expression cassette. These results show that our method will be of broad use throughout the field of metabolic engineering.

Combinatorial Screening for Transgenic Yeasts with High Cellulase Activities in Combination with a Tunable Expression System

Science.gov (United States)

Ito, Yoichiro; Yamanishi, Mamoru; Ikeuchi, Akinori; Imamura, Chie; Matsuyama, Takashi

2015-01-01

Combinatorial screening used together with a broad library of gene expression cassettes is expected to produce a powerful tool for the optimization of the simultaneous expression of multiple enzymes. Recently, we proposed a highly tunable protein expression system that utilized multiple genome-integrated target genes to fine-tune enzyme expression in yeast cells. This tunable system included a library of expression cassettes each composed of three gene-expression control elements that in different combinations produced a wide range of protein expression levels. In this study, four gene expression cassettes with graded protein expression levels were applied to the expression of three cellulases: cellobiohydrolase 1, cellobiohydrolase 2, and endoglucanase 2. After combinatorial screening for transgenic yeasts simultaneously secreting these three cellulases, we obtained strains with higher cellulase expressions than a strain harboring three cellulase-expression constructs within one high-performance gene expression cassette. These results show that our method will be of broad use throughout the field of metabolic engineering. PMID:26692026

Human mammary progenitor cell fate decisions are productsof interactions with combinatorial microenvironments

DEFF Research Database (Denmark)

LaBarge, Mark A.; Nelson, Celeste M.; Villadsen, René

2009-01-01

factors, ECM, and other cells, as well as physical properties of the ECM. To understand regulation of fate decisions, therefore, would require a means of understanding carefully choreographed combinatorial interactions. Here we used microenvironment protein microarrays to functionally identify...... combinations of cell-extrinsic mammary gland proteins and ECM molecules that imposed specific cell fates on bipotent human mammary progenitor cells.Micropatterned cell culture surfaces were fabricated to distinguish between the instructive effects of cell-cell versus cell-ECM interactions, as well...

Resolving combinatorial ambiguities in dilepton t t¯ event topologies with constrained M2 variables

Science.gov (United States)

Debnath, Dipsikha; Kim, Doojin; Kim, Jeong Han; Kong, Kyoungchul; Matchev, Konstantin T.

2017-10-01

We advocate the use of on-shell constrained M2 variables in order to mitigate the combinatorial problem in supersymmetry-like events with two invisible particles at the LHC. We show that in comparison to other approaches in the literature, the constrained M2 variables provide superior ansätze for the unmeasured invisible momenta and therefore can be usefully applied to discriminate combinatorial ambiguities. We illustrate our procedure with the example of dilepton t t ¯ events. We critically review the existing methods based on the Cambridge MT 2 variable and MAOS reconstruction of invisible momenta, and show that their algorithm can be simplified without loss of sensitivity, due to a perfect correlation between events with complex solutions for the invisible momenta and events exhibiting a kinematic endpoint violation. Then we demonstrate that the efficiency for selecting the correct partition is further improved by utilizing the M2 variables instead. Finally, we also consider the general case when the underlying mass spectrum is unknown, and no kinematic endpoint information is available.

On language acquisition in speech and sign:development drives combinatorial structure in both modalities

Directory of Open Access Journals (Sweden)

Gary eMorgan

2014-11-01

Full Text Available Languages are composed of a conventionalized system of parts which allow speakers and signers to compose an infinite number of form-meaning mappings through phonological and morphological combinations. This level of linguistic organization distinguishes language from other communicative acts such as gestures. In contrast to signs, gestures are made up of meaning units that are mostly holistic. Children exposed to signed and spoken languages from early in life develop grammatical structure following similar rates and patterns. This is interesting, because signed languages are perceived and articulated in very different ways to their spoken counterparts with many signs displaying surface resemblances to gestures. The acquisition of forms and meanings in child signers and talkers might thus have been a different process. Yet in one sense both groups are faced with a similar problem: 'how do I make a language with combinatorial structure’? In this paper I argue first language development itself enables this to happen and by broadly similar mechanisms across modalities. Combinatorial structure is the outcome of phonological simplifications and productivity in using verb morphology by children in sign and speech.

Reward-based hypertension control by a synthetic brain-dopamine interface.

Science.gov (United States)

Rössger, Katrin; Charpin-El Hamri, Ghislaine; Fussenegger, Martin

2013-11-05

Synthetic biology has significantly advanced the design of synthetic trigger-controlled devices that can reprogram mammalian cells to interface with complex metabolic activities. In the brain, the neurotransmitter dopamine coordinates communication with target neurons via a set of dopamine receptors that control behavior associated with reward-driven learning. This dopamine transmission has recently been suggested to increase central sympathetic outflow, resulting in plasma dopamine levels that correlate with corresponding brain activities. By functionally rewiring the human dopamine receptor D1 (DRD1) via the second messenger cyclic adenosine monophosphate (cAMP) to synthetic promoters containing cAMP response element-binding protein 1(CREB1)-specific cAMP-responsive operator modules, we have designed a synthetic dopamine-sensitive transcription controller that reversibly fine-tunes specific target gene expression at physiologically relevant brain-derived plasma dopamine levels. Following implantation of circuit-transgenic human cell lines insulated by semipermeable immunoprotective microcontainers into mice, the designer device interfaced with dopamine-specific brain activities and produced a systemic expression response when the animal's reward system was stimulated by food, sexual arousal, or addictive drugs. Reward-triggered brain activities were able to remotely program peripheral therapeutic implants to produce sufficient amounts of the atrial natriuretic peptide, which reduced the blood pressure of hypertensive mice to the normal physiologic range. Seamless control of therapeutic transgenes by subconscious behavior may provide opportunities for treatment strategies of the future.

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.

Two projects in theoretical neuroscience: A convolution-based metric for neural membrane potentials and a combinatorial connectionist semantic network method

Science.gov (United States)

Evans, Garrett Nolan

In this work, I present two projects that both contribute to the aim of discovering how intelligence manifests in the brain. The first project is a method for analyzing recorded neural signals, which takes the form of a convolution-based metric on neural membrane potential recordings. Relying only on integral and algebraic operations, the metric compares the timing and number of spikes within recordings as well as the recordings' subthreshold features: summarizing differences in these with a single "distance" between the recordings. Like van Rossum's (2001) metric for spike trains, the metric is based on a convolution operation that it performs on the input data. The kernel used for the convolution is carefully chosen such that it produces a desirable frequency space response and, unlike van Rossum's kernel, causes the metric to be first order both in differences between nearby spike times and in differences between same-time membrane potential values: an important trait. The second project is a combinatorial syntax method for connectionist semantic network encoding. Combinatorial syntax has been a point on which those who support a symbol-processing view of intelligent processing and those who favor a connectionist view have had difficulty seeing eye-to-eye. Symbol-processing theorists have persuasively argued that combinatorial syntax is necessary for certain intelligent mental operations, such as reasoning by analogy. Connectionists have focused on the versatility and adaptability offered by self-organizing networks of simple processing units. With this project, I show that there is a way to reconcile the two perspectives and to ascribe a combinatorial syntax to a connectionist network. The critical principle is to interpret nodes, or units, in the connectionist network as bound integrations of the interpretations for nodes that they share links with. Nodes need not correspond exactly to neurons and may correspond instead to distributed sets, or assemblies, of

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

Science.gov (United States)

Velagapudi, Sai Pradeep; Disney, Matthew D

2014-03-21

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

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

Science.gov (United States)

Ciechonska, Marta; Grob, Alice; Isalan, Mark

2016-04-18

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

Combinatorial Alanine Substitution Enables Rapid Optimization of Cytochrome P450BM3 for Selective Hydroxylation of Large Substrates

KAUST Repository

Lewis, Jared C.; Mantovani, Simone M.; Fu, Yu; Snow, Christopher D.; Komor, Russell S.; Wong , Chi-Huey; Arnold, Frances H.

2010-01-01

Made for each other: Combinatorial alanine substitution of active site residues in a thermostable cytochrome P450BM3 variant was used to generate an enzyme that is active with large substrates. Selective hydroxylation of methoxymethylated

The World of Combinatorial Fuzzy Problems and the Efficiency of Fuzzy Approximation Algorithms

OpenAIRE

Yamakami, Tomoyuki

2015-01-01

We re-examine a practical aspect of combinatorial fuzzy problems of various types, including search, counting, optimization, and decision problems. We are focused only on those fuzzy problems that take series of fuzzy input objects and produce fuzzy values. To solve such problems efficiently, we design fast fuzzy algorithms, which are modeled by polynomial-time deterministic fuzzy Turing machines equipped with read-only auxiliary tapes and write-only output tapes and also modeled by polynomia...