Combinatorial approaches to gene recognition.

PubMed

Roytberg, M A; Astakhova, T V; Gelfand, M S

1997-01-01

Recognition of genes via exon assembly approaches leads naturally to the use of dynamic programming. We consider the general graph-theoretical formulation of the exon assembly problem and analyze in detail some specific variants: multicriterial optimization in the case of non-linear gene-scoring functions; context-dependent schemes for scoring exons and related procedures for exon filtering; and highly specific recognition of arbitrary gene segments, oligonucleotide probes and polymerase chain reaction (PCR) primers.

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

PubMed

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).

Graphene Microcapsule Arrays for Combinatorial Electron Microscopy and Spectroscopy in Liquids

DOE PAGES

Yulaev, Alexander; Guo, Hongxuan; Strelcov, Evgheni; ...

2017-04-27

Atomic-scale thickness, molecular impermeability, low atomic number, and mechanical strength make graphene an ideal electron-transparent membrane for material characterization in liquids and gases with scanning electron microscopy and spectroscopy. Here in this paper, we present a novel sample platform made of an array of thousands of identical isolated graphene-capped microchannels with high aspect ratio. A combination of a global wide field of view with high resolution local imaging of the array allows for high throughput in situ studies as well as for combinatorial screening of solutions, liquid interfaces, and immersed samples. We demonstrate the capabilities of this platform by studyingmore » a pure water sample in comparison with alkali halide solutions, a model electrochemical plating process, and beam-induced crystal growth in liquid electrolyte. Spectroscopic characterization of liquid interfaces and immersed objects with Auger and X-ray fluorescence analysis through the graphene membrane are also demonstrated.« less

Measuring and Specifying Combinatorial Coverage of Test Input Configurations

PubMed Central

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

2015-01-01

A key issue in testing is how many tests are needed for a required level of coverage or fault detection. Estimates are often based on error rates in initial testing, or on code coverage. For example, tests may be run until a desired level of statement or branch coverage is achieved. Combinatorial methods present an opportunity for a different approach to estimating required test set size, using characteristics of the test set. This paper describes methods for estimating the coverage of, and ability to detect, t-way interaction faults of a test set based on a covering array. We also develop a connection between (static) combinatorial coverage and (dynamic) code coverage, such that if a specific condition is satisfied, 100% branch coverage is assured. Using these results, we propose practical recommendations for using combinatorial coverage in specifying test requirements. PMID:28133442

Analytical instrumentation infrastructure for combinatorial and high-throughput development of formulated discrete and gradient polymeric sensor materials arrays

NASA Astrophysics Data System (ADS)

Potyrailo, Radislav A.; Hassib, Lamyaa

2005-06-01

Multicomponent polymer-based formulations of optical sensor materials are difficult and time consuming to optimize using conventional approaches. To address these challenges, our long-term goal is to determine relationships between sensor formulation and sensor response parameters using new scientific methodologies. As the first step, we have designed and implemented an automated analytical instrumentation infrastructure for combinatorial and high-throughput development of polymeric sensor materials for optical sensors. Our approach is based on the fabrication and performance screening of discrete and gradient sensor arrays. Simultaneous formation of multiple sensor coatings into discrete 4×6, 6×8, and 8×12 element arrays (3-15μL volume per element) and their screening provides not only a well-recognized acceleration in the screening rate, but also considerably reduces or even eliminates sources of variability, which are randomly affecting sensors response during a conventional one-at-a-time sensor coating evaluation. The application of gradient sensor arrays provides additional capabilities for rapid finding of the optimal formulation parameters.

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.

PubMed

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.

A Comparison of Heuristic and Human Performance on Open Versions of the Traveling Salesperson Problem

ERIC Educational Resources Information Center

MacGregor, James N.; Chronicle, Edward P.; Ormerod, Thomas C.

2006-01-01

We compared the performance of three heuristics with that of subjects on variants of a well-known combinatorial optimization task, the Traveling Salesperson Problem (TSP). The present task consisted of finding the shortest path through an array of points from one side of the array to the other. Like the standard TSP, the task is computationally…

Toxicity and Detoxification Effects of Herbal Caowu via Ultra Performance Liquid Chromatography/Mass Spectrometry Metabolomics Analyzed using Pattern Recognition Method

PubMed Central

Yan, Yan; Zhang, Aihua; Dong, Hui; Yan, Guangli; Sun, Hui; Wu, Xiuhong; Han, Ying; Wang, Xijun

2017-01-01

Background: Caowu (Radix Aconiti kusnezoffii, CW), the root of Aconitum kusnezoffii Reichb., has widely used clinically in rheumatic arthritis, painful joints, and tumors for thousands of years. However, the toxicity of heart and central nervous system induced by CW still limited the application. Materials and Methods: Metabolomics was performed to identify the sensitive and reliable biomarkers and to characterize the phenotypically biochemical perturbations and potential mechanisms of CW-induced toxicity, and the detoxification by combinatorial intervention of CW with Gancao (Radix Glycyrrhizae) (CG), Baishao (Radix Paeoniae Alba) (CB), and Renshen (Radix Ginseng) (CR) was also analyzed by pattern recognition methods. Results: As a result, the metabolites were characterized and responsible for pentose and glucuronate interconversions, tryptophan metabolism, amino sugar and nucleotide sugar metabolism, taurine and hypotaurine metabolism, fructose and mannose metabolism, and starch and sucrose metabolism, six networks of which were the same to the metabolic pathways of Chuanwu (Radix Aconiti, CHW) group. The ascorbate and aldarate metabolism was also characterized by CW group. The urinary metabolomics also revealed CW-induced serious toxicity to heart and liver. Thirteen significant metabolites were identified and had validated as phenotypic toxicity biomarkers of CW, five biomarkers of which were commonly owned in Aconitum. The changes of toxicity metabolites obtained from combinatorial intervention of CG, CB, and CR also were analyzed to investigate the regulation degree of toxicity biomarkers adjusted by different combinatorial interventions at 6th month. Conclusion: Metabolomics analyses coupled with pattern recognition methods in the evaluation of drug toxicity and finding detoxification methods were highlighted in this work. SUMMARY Metabolomics was performed to characterize the biochemical potential mechanisms of Caowu toxicityThirteen significant metabolites were identified and validated as phenotypic toxicity biomarkers of CaowuMetabolite changes of toxicity obtained can be adjusted by different combinatorial interventions.Pattern recognition plot reflects the toxicity effects tendency of the urine metabolic fluctuations according to time after treatment of herbal Caowu. Abbreviations used: CW: Caowu (Radix Aconiti kusnezoffii); CHW: Chuanwu (Radix Aconiti); TCM: Traditional Chinese Medicine; CG: Caowu and Gancao; CB: Caowu and Baishao; CR: Caowu and Renshen; QC: Quality control; UPLC: Ultra performance liquid chromatography; MS: Mass spectrometry; PCA: Principal component analysis; PLS-DA: Partial least squares-discriminant analysis; OPLS: Orthogonal projection to latent structures analysis. PMID:29200734

Real-time monitoring of surface-initiated atom transfer radical polymerization using silicon photonic microring resonators: implications for combinatorial screening of polymer brush growth conditions.

PubMed

Limpoco, F Ted; Bailey, Ryan C

2011-09-28

We directly monitor in parallel and in real time the temporal profiles of polymer brushes simultaneously grown via multiple ATRP reaction conditions on a single substrate using arrays of silicon photonic microring resonators. In addition to probing relative polymerization rates, we show the ability to evaluate the dynamic properties of the in situ grown polymers. This presents a powerful new platform for studying modified interfaces that may allow for the combinatorial optimization of surface-initiated polymerization conditions.

Systems and methods for the combinatorial synthesis of novel materials

DOEpatents

Wu, Xin Di; Wang, Youqi; Goldwasser, Isy

2000-01-01

Methods and apparatus for the preparation of a substrate having an array of diverse materials in predefined regions thereon. A substrate having an array of diverse materials thereon is generally prepared by depositing components of target materials to predefined regions on the substrate, and, in some embodiments, simultaneously reacting the components to form at least two resulting materials. In particular, the present invention provides novel masking systems and methods for applying components of target materials onto a substrate in a combinatorial fashion, thus creating arrays of resulting materials that differ slightly in composition, stoichiometry, and/or thickness. Using the novel masking systems of the present invention, components can be delivered to each site in a uniform distribution, or in a gradient of stoichiometries, thicknesses, compositions, etc. Resulting materials which can be prepared using the methods and apparatus of the present invention include, for example, covalent network solids, ionic solids and molecular solids. Once prepared, these resulting materials can be screened sequentially, or in parallel, for useful properties including, for example, electrical, thermal, mechanical, morphological, optical, magnetic, chemical and other properties.

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

PubMed Central

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

Analytical validation of a psychiatric pharmacogenomic test.

PubMed

Jablonski, Michael R; King, Nina; Wang, Yongbao; Winner, Joel G; Watterson, Lucas R; Gunselman, Sandra; Dechairo, Bryan M

2018-05-01

The aim of this study was to validate the analytical performance of a combinatorial pharmacogenomics test designed to aid in the appropriate medication selection for neuropsychiatric conditions. Genomic DNA was isolated from buccal swabs. Twelve genes (65 variants/alleles) associated with psychotropic medication metabolism, side effects, and mechanisms of actions were evaluated by bead array, MALDI-TOF mass spectrometry, and/or capillary electrophoresis methods (GeneSight Psychotropic, Assurex Health, Inc.). The combinatorial pharmacogenomics test has a dynamic range of 2.5-20 ng/μl of input genomic DNA, with comparable performance for all assays included in the test. Both the precision and accuracy of the test were >99.9%, with individual gene components between 99.4 and 100%. This study demonstrates that the combinatorial pharmacogenomics test is robust and reproducible, making it suitable for clinical use.

Combinatorial algorithms for design of DNA arrays.

PubMed

Hannenhalli, Sridhar; Hubell, Earl; Lipshutz, Robert; Pevzner, Pavel A

2002-01-01

Optimal design of DNA arrays requires the development of algorithms with two-fold goals: reducing the effects caused by unintended illumination (border length minimization problem) and reducing the complexity of masks (mask decomposition problem). We describe algorithms that reduce the number of rectangles in mask decomposition by 20-30% as compared to a standard array design under the assumption that the arrangement of oligonucleotides on the array is fixed. This algorithm produces provably optimal solution for all studied real instances of array design. We also address the difficult problem of finding an arrangement which minimizes the border length and come up with a new idea of threading that significantly reduces the border length as compared to standard designs.

High-Density IgE Recognition of the Major Grass Pollen Allergen Phl p 1 Revealed with Single-Chain IgE Antibody Fragments Obtained by Combinatorial Cloning

PubMed Central

Madritsch, Christoph; Gadermaier, Elisabeth; Roder, Uwe W.; Lupinek, Christian; Valenta, Rudolf; Flicker, Sabine

2015-01-01

The timothy grass pollen allergen Phl p 1 belongs to the group 1 of highly cross-reactive grass pollen allergens with a molecular mass of ~25–30 kDa. Group 1 allergens are recognized by >95% of grass pollen allergic patients. We investigated the IgE recognition of Phl p 1 using allergen-specific IgE-derived single-chain variable Ab fragments (IgE-ScFvs) isolated from a combinatorial library constructed from PBMCs of a grass pollen–allergic patient. IgE-ScFvs reacted with recombinant Phl p 1 and natural group 1 grass pollen allergens. Using synthetic Phl p 1–derived peptides, the binding sites of two ScFvs were mapped to the N terminus of the allergen. In surface plasmon resonance experiments they showed comparable high-affinity binding to Phl p 1 as a complete human IgE-derived Ab recognizing the allergens’ C terminus. In a set of surface plasmon resonance experiments simultaneous allergen recognition of all three binders was demonstrated. Even in the presence of the three binders, allergic patients’ polyclonal IgE reacted with Phl p 1, indicating high-density IgE recognition of the Phl p 1 allergen. Our results show that multiple IgE Abs can bind with high density to Phl p 1, which may explain the high allergenic activity and sensitizing capacity of this allergen. PMID:25637023

Apertureless cantilever-free pen arrays for scanning photochemical printing.

PubMed

Zhou, Yu; Xie, Zhuang; Brown, Keith A; Park, Daniel J; Zhou, Xiaozhu; Chen, Peng-Cheng; Hirtz, Michael; Lin, Qing-Yuan; Dravid, Vinayak P; Schatz, George C; Zheng, Zijian; Mirkin, Chad A

2015-02-25

A novel, apertureless, cantilever-free pen array can be used for dual scanning photochemical and molecular printing. Serial writing with light is enabled by combining self-focusing pyramidal pens with an opaque backing between pens. The elastomeric pens also afford force-tuned illumination and simultaneous delivery of materials and optical energy. These attributes make the technique a promising candidate for maskless high-resolution photopatterning and combinatorial chemistry. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Molecular mechanisms of floral organ specification by MADS domain proteins.

PubMed

Yan, Wenhao; Chen, Dijun; Kaufmann, Kerstin

2016-02-01

Flower development is a model system to understand organ specification in plants. The identities of different types of floral organs are specified by homeotic MADS transcription factors that interact in a combinatorial fashion. Systematic identification of DNA-binding sites and target genes of these key regulators show that they have shared and unique sets of target genes. DNA binding by MADS proteins is not based on 'simple' recognition of a specific DNA sequence, but depends on DNA structure and combinatorial interactions. Homeotic MADS proteins regulate gene expression via alternative mechanisms, one of which may be to modulate chromatin structure and accessibility in their target gene promoters. Copyright © 2015 Elsevier Ltd. All rights reserved.

Generation of Synthetic Copolymer Libraries by Combinatorial Assembly on Nucleic Acid Templates.

PubMed

Kong, Dehui; Yeung, Wayland; Hili, Ryan

2016-07-11

Recent advances in nucleic acid-templated copolymerization have expanded the scope of sequence-controlled synthetic copolymers beyond the molecular architectures witnessed in nature. This has enabled the power of molecular evolution to be applied to synthetic copolymer libraries to evolve molecular function ranging from molecular recognition to catalysis. This Review seeks to summarize different approaches available to generate sequence-defined monodispersed synthetic copolymer libraries using nucleic acid-templated polymerization. Key concepts and principles governing nucleic acid-templated polymerization, as well as the fidelity of various copolymerization technologies, will be described. The Review will focus on methods that enable the combinatorial generation of copolymer libraries and their molecular evolution for desired function.

Magnetohydrodynamic pump with a system for promoting flow of fluid in one direction

DOEpatents

Lemoff, Asuncion V [Union City, CA; Lee, Abraham P [Irvine, CA

2010-07-13

A magnetohydrodynamic pump for pumping a fluid. The pump includes a microfluidic channel for channeling the fluid, a MHD electrode/magnet system operatively connected to the microfluidic channel, and a system for promoting flow of the fluid in one direction in the microfluidic channel. The pump has uses in the medical and biotechnology industries for blood-cell-separation equipment, biochemical assays, chemical synthesis, genetic analysis, drug screening, an array of antigen-antibody reactions, combinatorial chemistry, drug testing, medical and biological diagnostics, and combinatorial chemistry. The pump also has uses in electrochromatography, surface micromachining, laser ablation, inkjet printers, and mechanical micromilling.

Finding the Right Candidate for the Right Position: A Fast NMR-Assisted Combinatorial Method for Optimizing Nucleic Acids Binders.

PubMed

Jiménez-Moreno, Ester; Montalvillo-Jiménez, Laura; Santana, Andrés G; Gómez, Ana M; Jiménez-Osés, Gonzalo; Corzana, Francisco; Bastida, Agatha; Jiménez-Barbero, Jesús; Cañada, Francisco Javier; Gómez-Pinto, Irene; González, Carlos; Asensio, Juan Luis

2016-05-25

Development of strong and selective binders from promiscuous lead compounds represents one of the most expensive and time-consuming tasks in drug discovery. We herein present a novel fragment-based combinatorial strategy for the optimization of multivalent polyamine scaffolds as DNA/RNA ligands. Our protocol provides a quick access to a large variety of regioisomer libraries that can be tested for selective recognition by combining microdialysis assays with simple isotope labeling and NMR experiments. To illustrate our approach, 20 small libraries comprising 100 novel kanamycin-B derivatives have been prepared and evaluated for selective binding to the ribosomal decoding A-Site sequence. Contrary to the common view of NMR as a low-throughput technique, we demonstrate that our NMR methodology represents a valuable alternative for the detection and quantification of complex mixtures, even integrated by highly similar or structurally related derivatives, a common situation in the context of a lead optimization process. Furthermore, this study provides valuable clues about the structural requirements for selective A-site recognition.

Counting It Twice.

ERIC Educational Resources Information Center

Schattschneider, Doris

1991-01-01

Provided are examples from many domains of mathematics that illustrate the Fubini Principle in its discrete version: the value of a summation over a rectangular array is independent of the order of summation. Included are: counting using partitions as in proof by pictures, combinatorial arguments, indirect counting as in the inclusion-exclusion…

Experimental Design for Combinatorial and High Throughput Materials Development

NASA Astrophysics Data System (ADS)

Cawse, James N.

2002-12-01

In the past decade, combinatorial and high throughput experimental methods have revolutionized the pharmaceutical industry, allowing researchers to conduct more experiments in a week than was previously possible in a year. Now high throughput experimentation is rapidly spreading from its origins in the pharmaceutical world to larger industrial research establishments such as GE and DuPont, and even to smaller companies and universities. Consequently, researchers need to know the kinds of problems, desired outcomes, and appropriate patterns for these new strategies. Editor James Cawse's far-reaching study identifies and applies, with specific examples, these important new principles and techniques. Experimental Design for Combinatorial and High Throughput Materials Development progresses from methods that are now standard, such as gradient arrays, to mathematical developments that are breaking new ground. The former will be particularly useful to researchers entering the field, while the latter should inspire and challenge advanced practitioners. The book's contents are contributed by leading researchers in their respective fields. Chapters include: -High Throughput Synthetic Approaches for the Investigation of Inorganic Phase Space -Combinatorial Mapping of Polymer Blends Phase Behavior -Split-Plot Designs -Artificial Neural Networks in Catalyst Development -The Monte Carlo Approach to Library Design and Redesign This book also contains over 200 useful charts and drawings. Industrial chemists, chemical engineers, materials scientists, and physicists working in combinatorial and high throughput chemistry will find James Cawse's study to be an invaluable resource.

Understanding Single-Stranded Telomere End Binding by an Essential Protein

DTIC Science & Technology

2000-08-01

BioPharma Inc., 1885 33rd Street, Boulder, CO 80301 Traditional sequential medicinal chemistry methods have been augmented by combinatorial synthesis...on the same wells that were being analyzed in parallel by RP-HPLC/UV for purity. The sampling protocol for purity determination at Array BioPharma is

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

PubMed

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.

Solubility Interactions and the Design of Chemically Selective Sorbent Coatings for Chemical Sensors and Arrays

DTIC Science & Technology

1990-07-27

sorptionpiezoelectric sorption 63 detector, surface acoustic wave, pattern recognition, array, 16. PRICE CODE molecular recognition , 17. SECURITY...1 PIEZOELECTRIC SORPTION DETECTORS ........................................................... 6 SOLUBILITY... SORPTION AND LINEAR SOLVATION ENERGY RELATIONSHIPS (LSER) ................................................................................... 9

32 bit digital optical computer - A hardware update

NASA Technical Reports Server (NTRS)

Guilfoyle, Peter S.; Carter, James A., III; Stone, Richard V.; Pape, Dennis R.

1990-01-01

Such state-of-the-art devices as multielement linear laser diode arrays, multichannel acoustooptic modulators, optical relays, and avalanche photodiode arrays, are presently applied to the implementation of a 32-bit supercomputer's general-purpose optical central processing architecture. Shannon's theorem, Morozov's control operator method (in conjunction with combinatorial arithmetic), and DeMorgan's law have been used to design an architecture whose 100 MHz clock renders it fully competitive with emerging planar-semiconductor technology. Attention is given to the architecture's multichannel Bragg cells, thermal design and RF crosstalk considerations, and the first and second anamorphic relay legs.

Combinatorial wetting in colour: an optofluidic nose.

PubMed

Raymond, Kevin P; Burgess, Ian B; Kinney, Mackenzie H; Lončar, Marko; Aizenberg, Joanna

2012-10-07

We present a colourimetric litmus test for simple differentiation of organic liquids based on wetting, which achieves chemical specificity without a significant sacrifice in portability or ease-of-use. Chemical specificity is derived from the combination of colourimetric wetting patterns produced by liquids in an array of inverse opal films, each having a graded wettability, but using different surface groups to define that gradient.

2D photonic crystal complete band gap search using a cyclic cellular automaton refination

NASA Astrophysics Data System (ADS)

González-García, R.; Castañón, G.; Hernández-Figueroa, H. E.

2014-11-01

We present a refination method based on a cyclic cellular automaton (CCA) that simulates a crystallization-like process, aided with a heuristic evolutionary method called differential evolution (DE) used to perform an ordered search of full photonic band gaps (FPBGs) in a 2D photonic crystal (PC). The solution is proposed as a combinatorial optimization of the elements in a binary array. These elements represent the existence or absence of a dielectric material surrounded by air, thus representing a general geometry whose search space is defined by the number of elements in such array. A block-iterative frequency-domain method was used to compute the FPBGs on a PC, when present. DE has proved to be useful in combinatorial problems and we also present an implementation feature that takes advantage of the periodic nature of PCs to enhance the convergence of this algorithm. Finally, we used this methodology to find a PC structure with a 19% bandgap-to-midgap ratio without requiring previous information of suboptimal configurations and we made a statistical study of how it is affected by disorder in the borders of the structure compared with a previous work that uses a genetic algorithm.

Laser direct writing of combinatorial libraries of idealized cellular constructs: Biomedical applications

NASA Astrophysics Data System (ADS)

Schiele, Nathan R.; Koppes, Ryan A.; Corr, David T.; Ellison, Karen S.; Thompson, Deanna M.; Ligon, Lee A.; Lippert, Thomas K. M.; Chrisey, Douglas B.

2009-03-01

The ability to control cell placement and to produce idealized cellular constructs is essential for understanding and controlling intercellular processes and ultimately for producing engineered tissue replacements. We have utilized a novel intra-cavity variable aperture excimer laser operated at 193 nm to reproducibly direct write mammalian cells with micrometer resolution to form a combinatorial array of idealized cellular constructs. We deposited patterns of human dermal fibroblasts, mouse myoblasts, rat neural stem cells, human breast cancer cells, and bovine pulmonary artery endothelial cells to study aspects of collagen network formation, breast cancer progression, and neural stem cell proliferation, respectively. Mammalian cells were deposited by matrix assisted pulsed laser evaporation direct write from ribbons comprised of a UV transparent quartz coated with either a thin layer of extracellular matrix or triazene as a dynamic release layer using CAD/CAM control. We demonstrate that through optical imaging and incorporation of a machine vision algorithm, specific cells on the ribbon can be laser deposited in spatial coherence with respect to geometrical arrays and existing cells on the receiving substrate. Having the ability to direct write cells into idealized cellular constructs can help to answer many biomedical questions and advance tissue engineering and cancer research.

Combination Across Domains: An MEG Investigation into the Relationship between Mathematical, Pictorial, and Linguistic Processing

PubMed Central

Bemis, Douglas K.; Pylkkänen, Liina

2013-01-01

Debates surrounding the evolution of language often hinge upon its relationship to cognition more generally and many investigations have attempted to demark the boundary between the two. Though results from these studies suggest that language may recruit domain-general mechanisms during certain types of complex processing, the domain-generality of basic combinatorial mechanisms that lie at the core of linguistic processing is still unknown. Our previous work (Bemis and Pylkkänen, 2011, 2012) used magnetoencephalography to isolate neural activity associated with the simple composition of an adjective and a noun (“red boat”) and found increased activity during this processing localized to the left anterior temporal lobe (lATL), ventro-medial prefrontal cortex (vmPFC), and left angular gyrus (lAG). The present study explores the domain-generality of these effects and their associated combinatorial mechanisms through two parallel non-linguistic combinatorial tasks designed to be as minimal and natural as the linguistic paradigm. In the first task, we used pictures of colored shapes to elicit combinatorial conceptual processing similar to that evoked by the linguistic expressions and find increased activity again localized to the vmPFC during combinatorial processing. This result suggests that a domain-general semantic combinatorial mechanism operates during basic linguistic composition, and that activity generated by its processing localizes to the vmPFC. In the second task, we recorded neural activity as subjects performed simple addition between two small numerals. Consistent with a wide array of recent results, we find no effects related to basic addition that coincide with our linguistic effects and instead find increased activity localized to the intraparietal sulcus. This result suggests that the scope of the previously identified linguistic effects is restricted to compositional operations and does not extend generally to all tasks that are merely similar in form. PMID:23293621

Biomolecular Recognition of Semiconductors and Magnetic Materials to Assemble Nanoparticle Heterostructures

DTIC Science & Technology

2002-01-01

shown that engineered viruses can recognize specific semiconductor surfaces through the selection by combinatorial phage display method. These specific... phage display libraries. The screening method selected for binding affinity of a population of random peptides displayed as part of the pIII minor coat...shorter spacing than expected distance ( M13 phage length: 880 nm) corresponds to the length scale imposed by the phage which formed the tilted

A Mathematical Framework for Image Analysis

DTIC Science & Technology

1991-08-01

The results reported here were derived from the research project ’A Mathematical Framework for Image Analysis ’ supported by the Office of Naval...Research, contract N00014-88-K-0289 to Brown University. A common theme for the work reported is the use of probabilistic methods for problems in image ... analysis and image reconstruction. Five areas of research are described: rigid body recognition using a decision tree/combinatorial approach; nonrigid

Performance evaluation of coherent Ising machines against classical neural networks

NASA Astrophysics Data System (ADS)

Haribara, Yoshitaka; Ishikawa, Hitoshi; Utsunomiya, Shoko; Aihara, Kazuyuki; Yamamoto, Yoshihisa

2017-12-01

The coherent Ising machine is expected to find a near-optimal solution in various combinatorial optimization problems, which has been experimentally confirmed with optical parametric oscillators and a field programmable gate array circuit. The similar mathematical models were proposed three decades ago by Hopfield et al in the context of classical neural networks. In this article, we compare the computational performance of both models.

Optimizing Sensor and Actuator Arrays for ASAC Noise Control

NASA Technical Reports Server (NTRS)

Palumbo, Dan; Cabell, Ran

2000-01-01

This paper summarizes the development of an approach to optimizing the locations for arrays of sensors and actuators in active noise control systems. A type of directed combinatorial search, called Tabu Search, is used to select an optimal configuration from a much larger set of candidate locations. The benefit of using an optimized set is demonstrated. The importance of limiting actuator forces to realistic levels when evaluating the cost function is discussed. Results of flight testing an optimized system are presented. Although the technique has been applied primarily to Active Structural Acoustic Control systems, it can be adapted for use in other active noise control implementations.

Designing a multiroute synthesis scheme in combinatorial chemistry.

PubMed

Akavia, Adi; Senderowitz, Hanoch; Lerner, Alon; Shamir, Ron

2004-01-01

Solid-phase mix-and-split combinatorial synthesis is often used to produce large arrays of compounds to be tested during the various stages of the drug development process. This method can be represented by a synthesis graph in which nodes correspond to grow operations and arcs to beads transferred among the different reaction vessels. In this work, we address the problem of designing such a graph which maximizes the number of produced target compounds (namely, compounds out of an input library of desired molecules), given constraints on the number of beads used for library synthesis and on the number of reaction vessels available for concurrent grow steps. We present a heuristic based on a discrete search for solving this problem, test our solution on several data sets, explore its behavior, and show that it achieves good performance.

Intelligent data processing of an ultrasonic sensor system for pattern recognition improvements

NASA Astrophysics Data System (ADS)

Na, Seung You; Park, Min-Sang; Hwang, Won-Gul; Kee, Chang-Doo

1999-05-01

Though conventional time-of-flight ultrasonic sensor systems are popular due to the advantages of low cost and simplicity, the usage of the sensors is rather narrowly restricted within object detection and distance readings. There is a strong need to enlarge the amount of environmental information for mobile applications to provide intelligent autonomy. Wide sectors of such neighboring object recognition problems can be satisfactorily handled with coarse vision data such as sonar maps instead of accurate laser or optic measurements. For the usage of object pattern recognition, ultrasonic senors have inherent shortcomings of poor directionality and specularity which result in low spatial resolution and indistinctiveness of object patterns. To resolve these problems an array of increased number of sensor elements has been used for large objects. In this paper we propose a method of sensor array system with improved recognition capability using electronic circuits accompanying the sensor array and neuro-fuzzy processing of data fusion. The circuit changes transmitter output voltages of array elements in several steps. Relying upon the known sensor characteristics, a set of different return signals from neighboring senors is manipulated to provide an enhanced pattern recognition in the aspects of inclination angle, size and shift as well as distance of objects. The results show improved resolution of the measurements for smaller targets.

Electronic single-molecule identification of carbohydrate isomers by recognition tunnelling

NASA Astrophysics Data System (ADS)

Im, Jongone; Biswas, Sovan; Liu, Hao; Zhao, Yanan; Sen, Suman; Biswas, Sudipta; Ashcroft, Brian; Borges, Chad; Wang, Xu; Lindsay, Stuart; Zhang, Peiming

2016-12-01

Carbohydrates are one of the four main building blocks of life, and are categorized as monosaccharides (sugars), oligosaccharides and polysaccharides. Each sugar can exist in two alternative anomers (in which a hydroxy group at C-1 takes different orientations) and each pair of sugars can form different epimers (isomers around the stereocentres connecting the sugars). This leads to a vast combinatorial complexity, intractable to mass spectrometry and requiring large amounts of sample for NMR characterization. Combining measurements of collision cross section with mass spectrometry (IM-MS) helps, but many isomers are still difficult to separate. Here, we show that recognition tunnelling (RT) can classify many anomers and epimers via the current fluctuations they produce when captured in a tunnel junction functionalized with recognition molecules. Most importantly, RT is a nanoscale technique utilizing sub-picomole quantities of analyte. If integrated into a nanopore, RT would provide a unique approach to sequencing linear polysaccharides.

Tailoring gas sensor arrays via the design of short peptides sequences as binding elements.

PubMed

Mascini, Marcello; Pizzoni, Daniel; Perez, German; Chiarappa, Emilio; Di Natale, Corrado; Pittia, Paola; Compagnone, Dario

2017-07-15

A semi-combinatorial virtual approach was used to prepare peptide-based gas sensors with binding properties towards five different chemical classes (alcohols, aldehydes, esters, hydrocarbons and ketones). Molecular docking simulations were conducted for a complete tripeptide library (8000 elements) versus 58 volatile compounds belonging to those five chemical classes. By maximizing the differences between chemical classes, a subset of 120 tripeptides was extracted and used as scaffolds for generating a combinatorial library of 7912 tetrapeptides. This library was processed in an analogous way to the former. Five tetrapeptides (IHRI, KSDS, LGFD, TGKF and WHVS) were chosen depending on their virtual affinity and cross-reactivity for the experimental step. The five peptides were covalently bound to gold nanoparticles by adding a terminal cysteine to each tetrapeptide and deposited onto 20MHz quartz crystal microbalances to construct the gas sensors. The behavior of peptides after this chemical modification was simulated at the pH range used in the immobilization step. ΔF signals analyzed by principal component analysis matched the virtually screened data. The array was able to clearly discriminate the 13 volatile compounds tested based on their hydrophobicity and hydrophilicity molecules as well as the molecular weight. Copyright © 2016 Elsevier B.V. All rights reserved.

Causal gene identification using combinatorial V-structure search.

PubMed

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 pattern recognition approach to transistor array parameter variance

NASA Astrophysics Data System (ADS)

da F. Costa, Luciano; Silva, Filipi N.; Comin, Cesar H.

2018-06-01

The properties of semiconductor devices, including bipolar junction transistors (BJTs), are known to vary substantially in terms of their parameters. In this work, an experimental approach, including pattern recognition concepts and methods such as principal component analysis (PCA) and linear discriminant analysis (LDA), was used to experimentally investigate the variation among BJTs belonging to integrated circuits known as transistor arrays. It was shown that a good deal of the devices variance can be captured using only two PCA axes. It was also verified that, though substantially small variation of parameters is observed for BJT from the same array, larger variation arises between BJTs from distinct arrays, suggesting the consideration of device characteristics in more critical analog designs. As a consequence of its supervised nature, LDA was able to provide a substantial separation of the BJT into clusters, corresponding to each transistor array. In addition, the LDA mapping into two dimensions revealed a clear relationship between the considered measurements. Interestingly, a specific mapping suggested by the PCA, involving the total harmonic distortion variation expressed in terms of the average voltage gain, yielded an even better separation between the transistor array clusters. All in all, this work yielded interesting results from both semiconductor engineering and pattern recognition perspectives.

Introduction of statistical information in a syntactic analyzer for document image recognition

NASA Astrophysics Data System (ADS)

Maroneze, André O.; Coüasnon, Bertrand; Lemaitre, Aurélie

2011-01-01

This paper presents an improvement to document layout analysis systems, offering a possible solution to Sayre's paradox (which states that an element "must be recognized before it can be segmented; and it must be segmented before it can be recognized"). This improvement, based on stochastic parsing, allows integration of statistical information, obtained from recognizers, during syntactic layout analysis. We present how this fusion of numeric and symbolic information in a feedback loop can be applied to syntactic methods to improve document description expressiveness. To limit combinatorial explosion during exploration of solutions, we devised an operator that allows optional activation of the stochastic parsing mechanism. Our evaluation on 1250 handwritten business letters shows this method allows the improvement of global recognition scores.

High-Throughput Genetic Analysis and Combinatorial Chiral Separations Based on Capillary Electrophoresis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhong, Wenwan

2003-01-01

Capillary electrophoresis (CE) offers many advantages over conventional analytical methods, such as speed, simplicity, high resolution, low cost, and small sample consumption, especially for the separation of enantiomers. However, chiral method developments still can be time consuming and tedious. They designed a comprehensive enantioseparation protocol employing neutral and sulfated cyclodextrins as chiral selectors for common basic, neutral, and acidic compounds with a 96-capillary array system. By using only four judiciously chosen separation buffers, successful enantioseparations were achieved for 49 out of 54 test compounds spanning a large variety of pKs and structures. Therefore, unknown compounds can be screened in thismore » manner to identify optimal enantioselective conditions in just one rn. In addition to superior separation efficiency for small molecules, CE is also the most powerful technique for DNA separations. Using the same multiplexed capillary system with UV absorption detection, the sequence of a short DNA template can be acquired without any dye-labels. Two internal standards were utilized to adjust the migration time variations among capillaries, so that the four electropherograms for the A, T, C, G Sanger reactions can be aligned and base calling can be completed with a high level of confidence. the CE separation of DNA can be applied to study differential gene expression as well. Combined with pattern recognition techniques, small variations among electropherograms obtained by the separation of cDNA fragments produced from the total RNA samples of different human tissues can be revealed. These variations reflect the differences in total RNA expression among tissues. Thus, this Ce-based approach can serve as an alternative to the DNA array techniques in gene expression analysis.« less

ChIP-less analysis of chromatin states.

PubMed

Su, Zhangli; Boersma, Melissa D; Lee, Jin-Hee; Oliver, Samuel S; Liu, Shichong; Garcia, Benjamin A; Denu, John M

2014-01-01

Histone post-translational modifications (PTMs) are key epigenetic regulators in chromatin-based processes. Increasing evidence suggests that vast combinations of PTMs exist within chromatin histones. These complex patterns, rather than individual PTMs, are thought to define functional chromatin states. However, the ability to interrogate combinatorial histone PTM patterns at the nucleosome level has been limited by the lack of direct molecular tools. Here we demonstrate an efficient, quantitative, antibody-free, chromatin immunoprecipitation-less (ChIP-less) method for interrogating diverse epigenetic states. At the heart of the workflow are recombinant chromatin reader domains, which target distinct chromatin states with combinatorial PTM patterns. Utilizing a newly designed combinatorial histone peptide microarray, we showed that three reader domains (ATRX-ADD, ING2-PHD and AIRE-PHD) displayed greater specificity towards combinatorial PTM patterns than corresponding commercial histone antibodies. Such specific recognitions were employed to develop a chromatin reader-based affinity enrichment platform (matrix-assisted reader chromatin capture, or MARCC). We successfully applied the reader-based platform to capture unique chromatin states, which were quantitatively profiled by mass spectrometry to reveal interconnections between nucleosomal histone PTMs. Specifically, a highly enriched signature that harbored H3K4me0, H3K9me2/3, H3K79me0 and H4K20me2/3 within the same nucleosome was identified from chromatin enriched by ATRX-ADD. This newly reported PTM combination was enriched in heterochromatin, as revealed by the associated DNA. Our results suggest the broad utility of recombinant reader domains as an enrichment tool specific to combinatorial PTM patterns, which are difficult to probe directly by antibody-based approaches. The reader affinity platform is compatible with several downstream analyses to investigate the physical coexistence of nucleosomal PTM states associated with specific genomic loci. Collectively, the reader-based workflow will greatly facilitate our understanding of how distinct chromatin states and reader domains function in gene regulatory mechanisms.

Combinatorial search for green and blue phosphors of high thermal stabilities under UV excitation based on the K(Sr1-x-y)PO4:Tb3+ xEu2+y system.

PubMed

Chan, Ting-Shan; Liu, Yao-Min; Liu, Ru-Shi

2008-01-01

The present investigation aims at the synthesis of KSr 1-x-y PO 4:Tb(3+) x Eu(2+) y phosphors using the combinatorial chemistry method. We have developed square-type arrays consisting of 121 compositions to investigate the optimum composition and luminescence properties of KSrPO 4 host matrix under 365 nm ultraviolet (UV) light. The optimized compositions of phosphors were found to be KSr 0.93PO 4:Tb(3+) 0.07 (green) and KSr 0.995PO 4:Eu(2+) 0.005 (blue). These phosphors showed good thermal luminescence stability better than commercially available YAG:Ce at temperature above 200 degrees C. The result indicates that the KSr 1-x-y PO 4:Tb(3+) x Eu (2+)y can be potentially useful as a UV radiation-converting phosphor for light-emitting diodes.

Combinatorial microfluidic droplet engineering for biomimetic material synthesis

PubMed Central

Bawazer, Lukmaan A.; McNally, Ciara S.; Empson, Christopher J.; Marchant, William J.; Comyn, Tim P.; Niu, Xize; Cho, Soongwon; McPherson, Michael J.; Binks, Bernard P.; deMello, Andrew; Meldrum, Fiona C.

2016-01-01

Although droplet-based systems are used in a wide range of technologies, opportunities for systematically customizing their interface chemistries remain relatively unexplored. This article describes a new microfluidic strategy for rapidly tailoring emulsion droplet compositions and properties. The approach uses a simple platform for screening arrays of droplet-based microfluidic devices and couples this with combinatorial selection of the droplet compositions. Through the application of genetic algorithms over multiple screening rounds, droplets with target properties can be rapidly generated. The potential of this method is demonstrated by creating droplets with enhanced stability, where this is achieved by selecting carrier fluid chemistries that promote titanium dioxide formation at the droplet interfaces. The interface is a mixture of amorphous and crystalline phases, and the resulting composite droplets are biocompatible, supporting in vitro protein expression in their interiors. This general strategy will find widespread application in advancing emulsion properties for use in chemistry, biology, materials, and medicine. PMID:27730209

Ag-NP@Ge-nanotaper/Si-micropillar ordered arrays as ultrasensitive and uniform surface enhanced Raman scattering substrates

NASA Astrophysics Data System (ADS)

Liu, Jing; Meng, Guowen; Li, Zhongbo; Huang, Zhulin; Li, Xiangdong

2015-10-01

Surface-enhanced Raman scattering (SERS) is considered to be an excellent candidate for analytical detection schemes, because of its molecular specificity, rapid response and high sensitivity. Here, SERS-substrates of Ag-nanoparticle (Ag-NP) decorated Ge-nanotapers grafted on hexagonally ordered Si-micropillar (denoted as Ag-NP@Ge-nanotaper/Si-micropillar) arrays are fabricated via a combinatorial process of two-step etching to achieve hexagonal Si-micropillar arrays, chemical vapor deposition of flocky Ge-nanotapers on each Si-micropillar and decoration of Ag-NPs onto the Ge-nanotapers through galvanic displacement. With high density three-dimensional (3D) ``hot spots'' created from the large quantities of the neighboring Ag-NPs and large-scale uniform morphology, the hierarchical Ag-NP@Ge-nanotaper/Si-micropillar arrays exhibit strong and reproducible SERS activity. Using our hierarchical 3D SERS-substrates, both methyl parathion (a commonly used pesticide) and PCB-2 (one congener of highly toxic polychlorinated biphenyls) with concentrations down to 10-7 M and 10-5 M have been detected respectively, showing great potential in SERS-based rapid trace-level detection of toxic organic pollutants in the environment.Surface-enhanced Raman scattering (SERS) is considered to be an excellent candidate for analytical detection schemes, because of its molecular specificity, rapid response and high sensitivity. Here, SERS-substrates of Ag-nanoparticle (Ag-NP) decorated Ge-nanotapers grafted on hexagonally ordered Si-micropillar (denoted as Ag-NP@Ge-nanotaper/Si-micropillar) arrays are fabricated via a combinatorial process of two-step etching to achieve hexagonal Si-micropillar arrays, chemical vapor deposition of flocky Ge-nanotapers on each Si-micropillar and decoration of Ag-NPs onto the Ge-nanotapers through galvanic displacement. With high density three-dimensional (3D) ``hot spots'' created from the large quantities of the neighboring Ag-NPs and large-scale uniform morphology, the hierarchical Ag-NP@Ge-nanotaper/Si-micropillar arrays exhibit strong and reproducible SERS activity. Using our hierarchical 3D SERS-substrates, both methyl parathion (a commonly used pesticide) and PCB-2 (one congener of highly toxic polychlorinated biphenyls) with concentrations down to 10-7 M and 10-5 M have been detected respectively, showing great potential in SERS-based rapid trace-level detection of toxic organic pollutants in the environment. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06001j

A programmable microfluidic static droplet array for droplet generation, transportation, fusion, storage, and retrieval.

PubMed

Jin, Si Hyung; Jeong, Heon-Ho; Lee, Byungjin; Lee, Sung Sik; Lee, Chang-Soo

2015-01-01

We present a programmable microfluidic static droplet array (SDA) device that can perform user-defined multistep combinatorial protocols. It combines the passive storage of aqueous droplets without any external control with integrated microvalves for discrete sample dispensing and dispersion-free unit operation. The addressable picoliter-volume reaction is systematically achieved by consecutively merging programmable sequences of reagent droplets. The SDA device is remarkably reusable and able to perform identical enzyme kinetic experiments at least 30 times via automated cross-contamination-free removal of droplets from individual hydrodynamic traps. Taking all these features together, this programmable and reusable universal SDA device will be a general microfluidic platform that can be reprogrammed for multiple applications.

Differential Effector Engagement by Oncogenic KRAS. | Office of Cancer Genomics

Cancer.gov

KRAS can bind numerous effector proteins, which activate different downstream signaling events. The best known are RAF, phosphatidylinositide (PI)-3' kinase, and RalGDS families, but many additional direct and indirect effectors have been reported. We have assessed how these effectors contribute to several major phenotypes in a quantitative way, using an arrayed combinatorial siRNA screen in which we knocked down 41 KRAS effectors nodes in 92 cell lines.

Domain repertoires as a tool to derive protein recognition rules.

PubMed

Zucconi, A; Panni, S; Paoluzi, S; Castagnoli, L; Dente, L; Cesareni, G

2000-08-25

Several approaches, some of which are described in this issue, have been proposed to assemble a complete protein interaction map. These are often based on high throughput methods that explore the ability of each gene product to bind any other element of the proteome of the organism. Here we propose that a large number of interactions can be inferred by revealing the rules underlying recognition specificity of a small number (a few hundreds) of families of protein recognition modules. This can be achieved through the construction and characterization of domain repertoires. A domain repertoire is assembled in a combinatorial fashion by allowing each amino acid position in the binding site of a given protein recognition domain to vary to include all the residues allowed at that position in the domain family. The repertoire is then searched by phage display techniques with any target of interest and from the primary structure of the binding site of the selected domains one derives rules that are used to infer the formation of complexes between natural proteins in the cell.

An artificial tongue fluorescent sensor array for identification and quantitation of various heavy metal ions.

PubMed

Xu, Wang; Ren, Changliang; Teoh, Chai Lean; Peng, Juanjuan; Gadre, Shubhankar Haribhau; Rhee, Hyun-Woo; Lee, Chi-Lik Ken; Chang, Young-Tae

2014-09-02

Herein, a small-molecule fluorescent sensor array for rapid identification of seven heavy metal ions was designed and synthesized, with its sensing mechanism mimicking that of a tongue. The photoinduced electron transfer and intramolecular charge transfer mechanism result in combinatorial interactions between sensor array and heavy metal ions, which lead to diversified fluorescence wavelength shifts and emission intensity changes. Upon principle component analysis (PCA), this result renders clear identification of each heavy metal ion on a 3D spatial dispersion graph. Further exploration provides a concentration-dependent pattern, allowing both qualitative and quantitative measurements of heavy metal ions. On the basis of this information, a "safe-zone" concept was proposed, which provides rapid exclusion of versatile hazardous species from clean water samples based on toxicity characteristic leaching procedure standards. This type of small-molecule fluorescent sensor array could open a new avenue for multiple heavy metal ion detection and simplified water quality analysis.

Combinatorial electrochemical cell array for high throughput screening of micro-fuel-cells and metal/air batteries.

PubMed

Jiang, Rongzhong

2007-07-01

An electrochemical cell array was designed that contains a common air electrode and 16 microanodes for high throughput screening of both fuel cells (based on polymer electrolyte membrane) and metal/air batteries (based on liquid electrolyte). Electrode materials can easily be coated on the anodes of the electrochemical cell array and screened by switching a graphite probe from one cell to the others. The electrochemical cell array was used to study direct methanol fuel cells (DMFCs), including high throughput screening of electrode catalysts and determination of optimum operating conditions. For screening of DMFCs, there is about 6% relative standard deviation (percentage of standard deviation versus mean value) for discharge current from 10 to 20 mAcm(2). The electrochemical cell array was also used to study tin/air batteries. The effect of Cu content in the anode electrode on the discharge performance of the tin/air battery was investigated. The relative standard deviations for screening of metal/air battery (based on zinc/air) are 2.4%, 3.6%, and 5.1% for discharge current at 50, 100, and 150 mAcm(2), respectively.

Efficient feature subset selection with probabilistic distance criteria. [pattern recognition

NASA Technical Reports Server (NTRS)

Chittineni, C. B.

1979-01-01

Recursive expressions are derived for efficiently computing the commonly used probabilistic distance measures as a change in the criteria both when a feature is added to and when a feature is deleted from the current feature subset. A combinatorial algorithm for generating all possible r feature combinations from a given set of s features in (s/r) steps with a change of a single feature at each step is presented. These expressions can also be used for both forward and backward sequential feature selection.

Optical tools for high-throughput screening of abrasion resistance of combinatorial libraries of organic coatings

NASA Astrophysics Data System (ADS)

Potyrailo, Radislav A.; Chisholm, Bret J.; Olson, Daniel R.; Brennan, Michael J.; Molaison, Chris A.

2002-02-01

Design, validation, and implementation of an optical spectroscopic system for high-throughput analysis of combinatorially developed protective organic coatings are reported. Our approach replaces labor-intensive coating evaluation steps with an automated system that rapidly analyzes 8x6 arrays of coating elements that are deposited on a plastic substrate. Each coating element of the library is 10 mm in diameter and 2 to 5 micrometers thick. Performance of coatings is evaluated with respect to their resistance to wear abrasion because this parameter is one of the primary considerations in end-use applications. Upon testing, the organic coatings undergo changes that are impossible to quantitatively predict using existing knowledge. Coatings are abraded using industry-accepted abrasion test methods at single-or multiple-abrasion conditions, followed by high- throughput analysis of abrasion-induced light scatter. The developed automated system is optimized for the analysis of diffusively scattered light that corresponds to 0 to 30% haze. System precision of 0.1 to 2.5% relative standard deviation provides capability for the reliable ranking of coatings performance. While the system was implemented for high-throughput screening of combinatorially developed organic protective coatings for automotive applications, it can be applied to a variety of other applications where materials ranking can be achieved using optical spectroscopic tools.

Two-dimensional parallel array technology as a new approach to automated combinatorial solid-phase organic synthesis

PubMed

Brennan; Biddison; Frauendorf; Schwarcz; Keen; Ecker; Davis; Tinder; Swayze

1998-01-01

An automated, 96-well parallel array synthesizer for solid-phase organic synthesis has been designed and constructed. The instrument employs a unique reagent array delivery format, in which each reagent utilized has a dedicated plumbing system. An inert atmosphere is maintained during all phases of a synthesis, and temperature can be controlled via a thermal transfer plate which holds the injection molded reaction block. The reaction plate assembly slides in the X-axis direction, while eight nozzle blocks holding the reagent lines slide in the Y-axis direction, allowing for the extremely rapid delivery of any of 64 reagents to 96 wells. In addition, there are six banks of fixed nozzle blocks, which deliver the same reagent or solvent to eight wells at once, for a total of 72 possible reagents. The instrument is controlled by software which allows the straightforward programming of the synthesis of a larger number of compounds. This is accomplished by supplying a general synthetic procedure in the form of a command file, which calls upon certain reagents to be added to specific wells via lookup in a sequence file. The bottle position, flow rate, and concentration of each reagent is stored in a separate reagent table file. To demonstrate the utility of the parallel array synthesizer, a small combinatorial library of hydroxamic acids was prepared in high throughput mode for biological screening. Approximately 1300 compounds were prepared on a 10 μmole scale (3-5 mg) in a few weeks. The resulting crude compounds were generally >80% pure, and were utilized directly for high throughput screening in antibacterial assays. Several active wells were found, and the activity was verified by solution-phase synthesis of analytically pure material, indicating that the system described herein is an efficient means for the parallel synthesis of compounds for lead discovery. Copyright 1998 John Wiley & Sons, Inc.

DESIGN OF A PATTERN RECOGNITION DIGITAL COMPUTER WITH APPLICATION TO THE AUTOMATIC SCANNING OF BUBBLE CHAMBER NEGATIVES

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCormick, B.H.; Narasimhan, R.

1963-01-01

The overall computer system contains three main parts: an input device, a pattern recognition unit (PRU), and a control computer. The bubble chamber picture is divided into a grid of st run. Concent 1-mm squares on the film. It is then processed in parallel in a two-dimensional array of 1024 identical processing modules (stalactites) of the PRU. The array can function as a two- dimensional shift register in which results of successive shifting operations can be accumulated. The pattern recognition process is generally controlled by a conventional arithmetic computer. (A.G.W.)

Molecular codes for neuronal individuality and cell assembly in the brain

PubMed Central

Yagi, Takeshi

2012-01-01

The brain contains an enormous, but finite, number of neurons. The ability of this limited number of neurons to produce nearly limitless neural information over a lifetime is typically explained by combinatorial explosion; that is, by the exponential amplification of each neuron's contribution through its incorporation into “cell assemblies” and neural networks. In development, each neuron expresses diverse cellular recognition molecules that permit the formation of the appropriate neural cell assemblies to elicit various brain functions. The mechanism for generating neuronal assemblies and networks must involve molecular codes that give neurons individuality and allow them to recognize one another and join appropriate networks. The extensive molecular diversity of cell-surface proteins on neurons is likely to contribute to their individual identities. The clustered protocadherins (Pcdh) is a large subfamily within the diverse cadherin superfamily. The clustered Pcdh genes are encoded in tandem by three gene clusters, and are present in all known vertebrate genomes. The set of clustered Pcdh genes is expressed in a random and combinatorial manner in each neuron. In addition, cis-tetramers composed of heteromultimeric clustered Pcdh isoforms represent selective binding units for cell-cell interactions. Here I present the mathematical probabilities for neuronal individuality based on the random and combinatorial expression of clustered Pcdh isoforms and their formation of cis-tetramers in each neuron. Notably, clustered Pcdh gene products are known to play crucial roles in correct axonal projections, synaptic formation, and neuronal survival. Their molecular and biological features induce a hypothesis that the diverse clustered Pcdh molecules provide the molecular code by which neuronal individuality and cell assembly permit the combinatorial explosion of networks that supports enormous processing capability and plasticity of the brain. PMID:22518100

Evidence for morphological composition in compound words using MEG.

PubMed

Brooks, Teon L; Cid de Garcia, Daniela

2015-01-01

Psycholinguistic and electrophysiological studies of lexical processing show convergent evidence for morpheme-based lexical access for morphologically complex words that involves early decomposition into their constituent morphemes followed by some combinatorial operation. Considering that both semantically transparent (e.g., sailboat) and semantically opaque (e.g., bootleg) compounds undergo morphological decomposition during the earlier stages of lexical processing, subsequent combinatorial operations should account for the difference in the contribution of the constituent morphemes to the meaning of these different word types. In this study we use magnetoencephalography (MEG) to pinpoint the neural bases of this combinatorial stage in English compound word recognition. MEG data were acquired while participants performed a word naming task in which three word types, transparent compounds (e.g., roadside), opaque compounds (e.g., butterfly), and morphologically simple words (e.g., brothel) were contrasted in a partial-repetition priming paradigm where the word of interest was primed by one of its constituent morphemes. Analysis of onset latency revealed shorter latencies to name compound words than simplex words when primed, further supporting a stage of morphological decomposition in lexical access. An analysis of the associated MEG activity uncovered a region of interest implicated in morphological composition, the Left Anterior Temporal Lobe (LATL). Only transparent compounds showed increased activity in this area from 250 to 470 ms. Previous studies using sentences and phrases have highlighted the role of LATL in performing computations for basic combinatorial operations. Results are in tune with decomposition models for morpheme accessibility early in processing and suggest that semantics play a role in combining the meanings of morphemes when their composition is transparent to the overall word meaning.

pK(a) based protonation states and microspecies for protein-ligand docking.

PubMed

ten Brink, Tim; Exner, Thomas E

2010-11-01

In this paper we present our reworked approach to generate ligand protonation states with our structure preparation tool SPORES (Structure PrOtonation and REcognition System). SPORES can be used for the preprocessing of proteins and protein-ligand complexes as e.g. taken from the Protein Data Bank as well as for the setup of 3D ligand databases. It automatically assigns atom and bond types, generates different protonation, tautomeric states as well as different stereoisomers. In the revised version, pKa calculations with the ChemAxon software MARVIN are used either to determine the likeliness of a combinatorial generated protonation state or to determine the titrable atoms used in the combinatorial approach. Additionally, the MARVIN software is used to predict microspecies distributions of ligand molecules. Docking studies were performed with our recently introduced program PLANTS (Protein-Ligand ANT System) on all protomers resulting from the three different selection methods for the well established CCDC/ASTEX clean data set demonstrating the usefulness of especially the latter approach.

pKa based protonation states and microspecies for protein-ligand docking

NASA Astrophysics Data System (ADS)

ten Brink, Tim; Exner, Thomas E.

2010-11-01

In this paper we present our reworked approach to generate ligand protonation states with our structure preparation tool SPORES (Structure PrOtonation and REcognition System). SPORES can be used for the preprocessing of proteins and protein-ligand complexes as e.g. taken from the Protein Data Bank as well as for the setup of 3D ligand databases. It automatically assigns atom and bond types, generates different protonation, tautomeric states as well as different stereoisomers. In the revised version, pKa calculations with the ChemAxon software MARVIN are used either to determine the likeliness of a combinatorial generated protonation state or to determine the titrable atoms used in the combinatorial approach. Additionally, the MARVIN software is used to predict microspecies distributions of ligand molecules. Docking studies were performed with our recently introduced program PLANTS (Protein-Ligand ANT System) on all protomers resulting from the three different selection methods for the well established CCDC/ASTEX clean data set demonstrating the usefulness of especially the latter approach.

Frontiers in Chemical Sensors: Novel Principles and Techniques

NASA Astrophysics Data System (ADS)

Orellana, Guillermo; Moreno-Bondi, Maria Cruz

This third volume of Springer Series on Chemical Sensors and Biosensors aims to enable the researcher or technologist to become acquainted with the latest principles and techniques that keep on enlarging the applications in this fascinating field. It deals with the novel luminescence lifetime-based techniques for interrogation of sensor arrays in high-throughput screening, cataluminescence, chemical sensing with hollow waveguides, new ways in sensor design and fabrication by means of either combinatorial methods or engineered indicator/support couples.

Diversity in recognition of glycans by F-type lectins and galectins: molecular, structural, and biophysical aspects

PubMed Central

Vasta, Gerardo R.; Ahmed, Hafiz; Bianchet, Mario A.; Fernández-Robledo, José A.; Amzel, L. Mario

2013-01-01

Although lectins are “hard-wired” in the germline, the presence of tandemly arrayed carbohydrate recognition domains (CRDs), of chimeric structures displaying distinct CRDs, of polymorphic genes resulting in multiple isoforms, and in some cases, of a considerable recognition plasticity of their carbohydrate binding sites, significantly expand the lectin ligand-recognition spectrum and lectin functional diversification. Analysis of structural/functional aspects of galectins and F-lectins—the most recently identified lectin family characterized by a unique CRD sequence motif (a distinctive structural fold) and nominal specificity for l-Fuc—has led to a greater understanding of self/nonself recognition by proteins with tandemly arrayed CRDs. For lectins with a single CRD, however, recognition of self and nonself glycans can only be rationalized in terms of protein oligomerization and ligand clustering and presentation. Spatial and temporal changes in lectin expression, secretion, and local concentrations in extracellular microenvironments, as well as structural diversity and spatial display of their carbohydrate ligands on the host or microbial cell surface, are suggestive of a dynamic interplay of their recognition and effector functions in development and immunity. PMID:22973821

Array-based sensing using nanoparticles: an alternative approach for cancer diagnostics.

PubMed

Le, Ngoc D B; Yazdani, Mahdieh; Rotello, Vincent M

2014-07-01

Array-based sensing using nanoparticles (NPs) provides an attractive alternative to specific biomarker-focused strategies for cancer diagnosis. The physical and chemical properties of NPs provide both the recognition and transduction capabilities required for biosensing. Array-based sensors utilize a combined response from the interactions between sensors and analytes to generate a distinct pattern (fingerprint) for each analyte. These interactions can be the result of either the combination of multiple specific biomarker recognition (specific binding) or multiple selective binding responses, known as chemical nose sensing. The versatility of the latter array-based sensing using NPs can facilitate the development of new personalized diagnostic methodologies in cancer diagnostics, a necessary evolution in the current healthcare system to better provide personalized treatments. This review will describe the basic principle of array-based sensors, along with providing examples of both invasive and noninvasive samples used in cancer diagnosis.

Hidden Markov models for character recognition.

PubMed

Vlontzos, J A; Kung, S Y

1992-01-01

A hierarchical system for character recognition with hidden Markov model knowledge sources which solve both the context sensitivity problem and the character instantiation problem is presented. The system achieves 97-99% accuracy using a two-level architecture and has been implemented using a systolic array, thus permitting real-time (1 ms per character) multifont and multisize printed character recognition as well as handwriting recognition.

Ta2O5-memristor synaptic array with winner-take-all method for neuromorphic pattern matching

NASA Astrophysics Data System (ADS)

Truong, Son Ngoc; Van Pham, Khoa; Yang, Wonsun; Min, Kyeong-Sik; Abbas, Yawar; Kang, Chi Jung; Shin, Sangho; Pedrotti, Ken

2016-08-01

Pattern matching or pattern recognition is one of the elemental components that constitute the very complicated recalling and remembering process in human's brain. To realize this neuromorphic pattern matching, we fabricated and tested a 3 × 3 memristor synaptic array with the winner-take-all method in this research. In the measurement, first, the 3 × 3 Ta2O5 memristor array is programmed to store [LLL], [LHH], and [HLH], where L is a low-resistance state and H is a high-resistance state, at the 1st, 2nd, and 3rd columns, respectively. After the programming, three input patterns, [111], [100], and [010], are applied to the memristor synaptic array. From the measurement results, we confirm that all three input patterns can be recognized well by using a twin memristor crossbar with synaptic arrays. This measurement can be thought of as the first real verification of the twin memristor crossbar with memristive synaptic arrays for neuromorphic pattern recognition.

Harmful Gas Recognition Exploiting a CTL Sensor Array

PubMed Central

Wang, Qihui; Xie, Lijun; Zhu, Bo; Zheng, Yao; Cao, Shihua

2013-01-01

In this paper, a novel cataluminescence (CTL)-based sensor array consisting of nine types of catalytic materials is developed for the recognition of several harmful gases, namely carbon monoxide, acetone, chloroform and toluene. First, the experimental setup is constructed by using sensing nanomaterials, a heating plate, a pneumatic pump, a gas flow meter, a digital temperature device, a camera and a BPCL Ultra Weak Chemiluminescence Analyzer. Then, unique CTL patterns for the four types of harmful gas are obtained from the sensor array. The harmful gases are successful recognized by the PCA method. The optimal conditions are also investigated. Finally, experimental results show high sensitivity, long-term stability and good linearity of the sensor array, which combined with simplicity, make our system a promising application in this field. PMID:24113681

Final Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chidambaram, Dev; Misra, Mano; Heske, Clemens

2014-12-21

The objectives included: Develop high efficiency metal oxide nanotubular array photo-anodes for generating hydrogen by water splitting; Develop density functional theory to understand the effect of the morphology of the nanotubes on the photo-electrochemical (PEC) properties of the photo-anodes; Develop kinetics and formation mechanism of the metal oxide nanotubes under different synthesis conditions; Develop combinatorial approach to prepare hybrid photo-anodes having multiple hetero-atoms incorporation in a single photo anode; Improve the durability of the material; and Scale up the laboratory demonstration to production unit.

Do dyslexic individuals present a reduced visual attention span? Evidence from visual recognition tasks of non-verbal multi-character arrays.

PubMed

Yeari, Menahem; Isser, Michal; Schiff, Rachel

2017-07-01

A controversy has recently developed regarding the hypothesis that developmental dyslexia may be caused, in some cases, by a reduced visual attention span (VAS). To examine this hypothesis, independent of phonological abilities, researchers tested the ability of dyslexic participants to recognize arrays of unfamiliar visual characters. Employing this test, findings were rather equivocal: dyslexic participants exhibited poor performance in some studies but normal performance in others. The present study explored four methodological differences revealed between the two sets of studies that might underlie their conflicting results. Specifically, in two experiments we examined whether a VAS deficit is (a) specific to recognition of multi-character arrays as wholes rather than of individual characters within arrays, (b) specific to characters' position within arrays rather than to characters' identity, or revealed only under a higher attention load due to (c) low-discriminable characters, and/or (d) characters' short exposure. Furthermore, in this study we examined whether pure dyslexic participants who do not have attention disorder exhibit a reduced VAS. Although comorbidity of dyslexia and attention disorder is common and the ability to sustain attention for a long time plays a major rule in the visual recognition task, the presence of attention disorder was neither evaluated nor ruled out in previous studies. Findings did not reveal any differences between the performance of dyslexic and control participants on eight versions of the visual recognition task. These findings suggest that pure dyslexic individuals do not present a reduced visual attention span.

Effects of filler type and content on mechanical properties of photopolymerizable composites measured across two-dimensional combinatorial arrays.

PubMed

Lin-Gibson, Sheng; Sung, Lipiin; Forster, Aaron M; Hu, Haiqing; Cheng, Yajun; Lin, Nancy J

2009-07-01

Multicomponent formulations coupled with complex processing conditions govern the final properties of photopolymerizable dental composites. In this study, a single test substrate was fabricated to support multiple formulations with a gradient in degree of conversion (DC), allowing the evaluation of multiple processing conditions and formulations on one specimen. Mechanical properties and damage response were evaluated as a function of filler type/content and irradiation. DC, surface roughness, modulus, hardness, scratch deformation and cytotoxicity were quantified using techniques including near-infrared spectroscopy, laser confocal scanning microscopy, depth-sensing indentation, scratch testing and cell viability. Scratch parameters (depth, width, percent recovery) were correlated to composite modulus and hardness. Total filler content, nanofiller and irradiation time/intensity all affected the final properties, with the dominant factor for improved properties being a higher DC. This combinatorial platform accelerates the screening of dental composites through the direct comparison of properties and processing conditions across the same sample.

Development of a poly(dimethylacrylamide) based matrix material for solid phase high density peptide array synthesis employing a laser based material transfer

NASA Astrophysics Data System (ADS)

Ridder, Barbara; Foertsch, Tobias C.; Welle, Alexander; Mattes, Daniela S.; von Bojnicic-Kninski, Clemens M.; Loeffler, Felix F.; Nesterov-Mueller, Alexander; Meier, Michael A. R.; Breitling, Frank

2016-12-01

Poly(dimethylacrylamide) (PDMA) based matrix materials were developed for laser-based in situ solid phase peptide synthesis to produce high density arrays. In this specific array synthesis approach, amino acid derivatives are embedded into a matrix material, serving as a ;solid; solvent material at room temperature. Then, a laser pulse transfers this mixture to the target position on a synthesis slide, where the peptide array is synthesized. Upon heating above the glass transition temperature of the matrix material, it softens, allowing diffusion of the amino acid derivatives to the synthesis surface and serving as a solvent for peptide bond formation. Here, we synthesized PDMA six-arm star polymers, offering the desired matrix material properties, using atom transfer radical polymerization. With the synthesized polymers as matrix material, we structured and synthesized arrays with combinatorial laser transfer. With densities of up to 20,000 peptide spots per cm2, the resolution could be increased compared to the commercially available standard matrix material. Time-of-Flight Secondary Ion Mass Spectrometry experiments revealed the penetration behavior of an amino acid derivative into the prepared acceptor synthesis surface and the effectiveness of the washing protocols.

Multiobjective optimization of combinatorial libraries.

PubMed

Agrafiotis, D K

2002-01-01

Combinatorial chemistry and high-throughput screening have caused a fundamental shift in the way chemists contemplate experiments. Designing a combinatorial library is a controversial art that involves a heterogeneous mix of chemistry, mathematics, economics, experience, and intuition. Although there seems to be little agreement as to what constitutes an ideal library, one thing is certain: only one property or measure seldom defines the quality of the design. In most real-world applications, a good experiment requires the simultaneous optimization of several, often conflicting, design objectives, some of which may be vague and uncertain. In this paper, we discuss a class of algorithms for subset selection rooted in the principles of multiobjective optimization. Our approach is to employ an objective function that encodes all of the desired selection criteria, and then use a simulated annealing or evolutionary approach to identify the optimal (or a nearly optimal) subset from among the vast number of possibilities. Many design criteria can be accommodated, including diversity, similarity to known actives, predicted activity and/or selectivity determined by quantitative structure-activity relationship (QSAR) models or receptor binding models, enforcement of certain property distributions, reagent cost and availability, and many others. The method is robust, convergent, and extensible, offers the user full control over the relative significance of the various objectives in the final design, and permits the simultaneous selection of compounds from multiple libraries in full- or sparse-array format.

Combinatorial materials research applied to the development of new surface coatings VII: An automated system for adhesion testing

NASA Astrophysics Data System (ADS)

Chisholm, Bret J.; Webster, Dean C.; Bennett, James C.; Berry, Missy; Christianson, David; Kim, Jongsoo; Mayo, Bret; Gubbins, Nathan

2007-07-01

An automated, high-throughput adhesion workflow that enables pseudobarnacle adhesion and coating/substrate adhesion to be measured on coating patches arranged in an array format on 4×8in.2 panels was developed. The adhesion workflow consists of the following process steps: (1) application of an adhesive to the coating array; (2) insertion of panels into a clamping device; (3) insertion of aluminum studs into the clamping device and onto coating surfaces, aligned with the adhesive; (4) curing of the adhesive; and (5) automated removal of the aluminum studs. Validation experiments comparing data generated using the automated, high-throughput workflow to data obtained using conventional, manual methods showed that the automated system allows for accurate ranking of relative coating adhesion performance.

Spatiotemporal Pixelization to Increase the Recognition Score of Characters for Retinal Prostheses

PubMed Central

Kim, Hyun Seok; Park, Kwang Suk

2017-01-01

Most of the retinal prostheses use a head-fixed camera and a video processing unit. Some studies proposed various image processing methods to improve visual perception for patients. However, previous studies only focused on using spatial information. The present study proposes a spatiotemporal pixelization method mimicking fixational eye movements to generate stimulation images for artificial retina arrays by combining spatial and temporal information. Input images were sampled with a resolution that was four times higher than the number of pixel arrays. We subsampled this image and generated four different phosphene images. We then evaluated the recognition scores of characters by sequentially presenting phosphene images with varying pixel array sizes (6 × 6, 8 × 8 and 10 × 10) and stimulus frame rates (10 Hz, 15 Hz, 20 Hz, 30 Hz, and 60 Hz). The proposed method showed the highest recognition score at a stimulus frame rate of approximately 20 Hz. The method also significantly improved the recognition score for complex characters. This method provides a new way to increase practical resolution over restricted spatial resolution by merging the higher resolution image into high-frame time slots. PMID:29073735

Screening combinatorial arrays of inorganic materials with spectroscopy or microscopy

DOEpatents

Schultz, Peter G.; Xiang, Xiaodong; Goldwasser, Isy

2004-02-03

Methods and apparatus for the preparation and use of a substrate having an array of diverse materials in predefined regions thereon. A substrate having an array of diverse materials thereon is generally prepared by delivering components of materials to predefined regions on a substrate, and simultaneously reacting the components to form at least two materials. Materials which can be prepared using the methods and apparatus of the present invention include, for example, covalent network solids, ionic solids and molecular solids. More particularly, materials which can be prepared using the methods and apparatus of the present invention include, for example, inorganic materials, intermetallic materials, metal alloys, ceramic materials, organic materials, organometallic materials, non-biological organic polymers, composite materials (e.g., inorganic composites, organic composites, or combinations thereof), etc. Once prepared, these materials can be screened for useful properties including, for example, electrical, thermal, mechanical, morphological, optical, magnetic, chemical, or other properties. Thus, the present invention provides methods for the parallel synthesis and analysis of novel materials having useful properties.

Polymer arrays from the combinatorial synthesis of novel materials

DOEpatents

Schultz, Peter G.; Xiang, Xiao-Dong; Goldwasser, Isy; Briceno, Gabriel; Sun, Xiao-Dong

2004-09-21

Methods and apparatus for the preparation and use of a substrate having an array of diverse materials in predefined regions thereon. A substrate having an array of diverse materials thereon is generally prepared by delivering components of materials to predefined regions on a substrate, and simultaneously reacting the components to form at least two materials. Materials which can be prepared using the methods and apparatus of the present invention include, for example, covalent network solids, ionic solids and molecular solids. More particularly, materials which can be prepared using the methods and apparatus of the present invention include, for example, inorganic materials, intermetallic materials, metal alloys, ceramic materials, organic materials, organometallic materials, non-biological organic polymers, composite materials (e.g., inorganic composites, organic composites, or combinations thereof), etc. Once prepared, these materials can be screened for useful properties including, for example, electrical, thermal, mechanical, morphological, optical, magnetic, chemical, or other properties. Thus, the present invention provides methods for the parallel synthesis and analysis of novel materials having useful properties.

Synthesis and screening combinatorial arrays of zeolites

DOEpatents

Schultz, Peter G.; Xiang, Xiaodong; Goldwasser, Isy

2003-11-18

Methods and apparatus for the preparation and use of a substrate having an array of diverse materials in predefined regions thereon. A substrate having an array of diverse materials thereon is generally prepared by delivering components of materials to predefined regions on a substrate, and simultaneously reacting the components to form at least two materials. Materials which can be prepared using the methods and apparatus of the present invention include, for example, covalent network solids, ionic solids and molecular solids. More particularly, materials which can be prepared using the methods and apparatus of the present invention include, for example, inorganic materials, intermetallic materials, metal alloys, ceramic materials, organic materials, organometallic materials, non-biological organic polymers, composite materials (e.g., inorganic composites, organic composites, or combinations thereof), etc. Once prepared, these materials can be screened for useful properties including, for example, electrical, thermal, mechanical, morphological, optical, magnetic, chemical, or other properties. Thus, the present invention provides methods for the parallel synthesis and analysis of novel materials having useful properties.

Probing the dynamic reversibility and generation of dynamic combinatorial libraries in the presence of bacterial model oligopeptides as templating guests of tetra-carbohydrazide macrocycles using electrospray mass spectrometry.

PubMed

Nour, Hany F; Islam, Tuhidul; Fernández-Lahore, Marcelo; Kuhnert, Nikolai

2012-12-30

Over the past few decades, bacterial resistance to antibiotics has emerged as a real threat to human health. Accordingly, there is an urgent demand for the development of innovative strategies for discovering new antibiotics. We present the first use of tetra-carbohydrazide cyclophane macrocycles in dynamic combinatorial chemistry (DCC) and molecular recognition as chiral hosts binding oligopeptides, which mimic bacterial cell wall. This study introduces an innovative application of electrospray ionisation time-of-flight mass spectrometry (ESI-TOF MS) to oligopeptides recognition using DCC. A small dynamic library composed of eight functionalised macrocycles has been generated in solution and all members were characterised by ESI-TOF MS. We also probed the dynamic reversibility and mechanism of formation of tetra-carbohydrazide cyclophanes in real-time using ESI-TOF MS. Dynamic reversibility of tetra-carbohydrazide cyclophanes is favored under thermodynamic control. The mechanism of formation of tetra-carbohydrazide cyclophanes involves key dialdehyde intermediates, which have been detected and assigned according to their high-resolution m/z values. Three members of the dynamic library bind efficiently in the gas phase to a selection of oligopeptides, unique to bacteria, allowing observation of host/guest complex ions in the gas phase. We probed the mechanism of the [2+2]-cyclocondensation reaction forming library members, proved dynamic reversibility of tetra-carbohydrazide cyclophanes and showed that complex ions formed between library members and hosts can be observed in the gas phase, allowing the solution of an important problem of biological interest. Copyright © 2012 John Wiley & Sons, Ltd.

Combinatorial peptide libraries and biometric score matrices permit the quantitative analysis of specific and degenerate interactions between clonotypic TCR and MHC peptide ligands.

PubMed

Zhao, Y; Gran, B; Pinilla, C; Markovic-Plese, S; Hemmer, B; Tzou, A; Whitney, L W; Biddison, W E; Martin, R; Simon, R

2001-08-15

The interaction of TCRs with MHC peptide ligands can be highly flexible, so that many different peptides are recognized by the same TCR in the context of a single restriction element. We provide a quantitative description of such interactions, which allows the identification of T cell epitopes and molecular mimics. The response of T cell clones to positional scanning synthetic combinatorial libraries is analyzed with a mathematical approach that is based on a model of independent contribution of individual amino acids to peptide Ag recognition. This biometric analysis compares the information derived from these libraries composed of trillions of decapeptides with all the millions of decapeptides contained in a protein database to rank and predict the most stimulatory peptides for a given T cell clone. We demonstrate the predictive power of the novel strategy and show that, together with gene expression profiling by cDNA microarrays, it leads to the identification of novel candidate autoantigens in the inflammatory autoimmune disease, multiple sclerosis.

A Combinatorial Kin Discrimination System in Bacillus subtilis.

PubMed

Lyons, Nicholas A; Kraigher, Barbara; Stefanic, Polonca; Mandic-Mulec, Ines; Kolter, Roberto

2016-03-21

Multicellularity inherently involves a number of cooperative behaviors that are potentially susceptible to exploitation but can be protected by mechanisms such as kin discrimination. Discrimination of kin from non-kin has been observed in swarms of the bacterium Bacillus subtilis, but the underlying molecular mechanism has been unknown. We used genetic, transcriptomic, and bioinformatic analyses to uncover kin recognition factors in this organism. Our results identified many molecules involved in cell-surface modification and antimicrobial production and response. These genes varied significantly in expression level and mutation phenotype among B. subtilis strains, suggesting interstrain variation in the exact kin discrimination mechanism used. Genome analyses revealed a substantial diversity of antimicrobial genes present in unique combinations in different strains, with many likely acquired by horizontal gene transfer. The dynamic combinatorial effect derived from this plethora of kin discrimination genes creates a tight relatedness cutoff for cooperation that has likely led to rapid diversification within the species. Our data suggest that genes likely originally selected for competitive purposes also generate preferential interactions among kin, thus stabilizing multicellular lifestyles. Copyright © 2016 Elsevier Ltd. All rights reserved.

Method for the electro-addressable functionalization of electrode arrays

DOEpatents

Harper, Jason C.; Polsky, Ronen; Dirk, Shawn M.; Wheeler, David R.; Arango, Dulce C.; Brozik, Susan M.

2015-12-15

A method for preparing an electrochemical biosensor uses bias-assisted assembly of unreactive -onium molecules on an electrode array followed by post-assembly electro-addressable conversion of the unreactive group to a chemical or biological recognition group. Electro-addressable functionalization of electrode arrays enables the multi-target electrochemical sensing of biological and chemical analytes.

64 x 64 thresholding photodetector array for optical pattern recognition

NASA Astrophysics Data System (ADS)

Langenbacher, Harry; Chao, Tien-Hsin; Shaw, Timothy; Yu, Jeffrey W.

1993-10-01

A high performance 32 X 32 peak detector array is introduced. This detector consists of a 32 X 32 array of thresholding photo-transistor cells, manufactured with a standard MOSIS digital 2-micron CMOS process. A built-in thresholding function that is able to perform 1024 thresholding operations in parallel strongly distinguishes this chip from available CCD detectors. This high speed detector offers responses from one to 10 milliseconds that is much higher than the commercially available CCD detectors operating at a TV frame rate. The parallel multiple peaks thresholding detection capability makes it particularly suitable for optical correlator and optoelectronically implemented neural networks. The principle of operation, circuit design and the performance characteristics are described. Experimental demonstration of correlation peak detection is also provided. Recently, we have also designed and built an advanced version of a 64 X 64 thresholding photodetector array chip. Experimental investigation of using this chip for pattern recognition is ongoing.

Baby, Where Did You Get Those Eyes?: IEEE Pulse talks with Mark Sagar about the new face of artificial intelligence.

PubMed

Campbell, Sarah

2015-01-01

Mark Sagar is changing the way we look at computers by giving them faces?disconcertingly realistic human faces. Sagar first gained widespread recognition for his pioneering work in rendering faces for Hollywood movies, including Avatar and King Kong. With a Ph.D. degree in bioengineering and two Academy Awards under his belt, Sagar now directs a research lab at the University of Auckland, New Zealand, a combinatorial hub where artificial intelligence (AI), neuroscience, computer science, philosophy, and cognitive psychology intersect in creating interactive, intelligent technologies.

Lipid-based nanotubes as functional architectures with embedded fluorescence and recognition capabilities.

PubMed

John, George; Mason, Megan; Ajayan, Pulickel M; Dordick, Jonathan S

2004-11-24

A limited combinatorial strategy was used to synthesize a small library of soft lipid-based materials ranging from structurally unordered fibers to highly uniform nanotubes. The latter nanotubes are comprised of a bilayer structure with interdigitated alkyl chains associated through hydrophobic interactions. These tubes contain accessible 2,6-diaminopyridine linkers that can interact with thymidine and related nucleosides through multipoint hydrogen bonding, thereby quenching the intrinsic fluorescence of the aromatic linker. These results are the first example of a systematic strategy to design functional lipid nanotubes with precise structural and functional features.

Single particle electrochemical sensors and methods of utilization

DOEpatents

Schoeniger, Joseph [Oakland, CA; Flounders, Albert W [Berkeley, CA; Hughes, Robert C [Albuquerque, NM; Ricco, Antonio J [Los Gatos, CA; Wally, Karl [Lafayette, CA; Kravitz, Stanley H [Placitas, NM; Janek, Richard P [Oakland, CA

2006-04-04

The present invention discloses an electrochemical device for detecting single particles, and methods for using such a device to achieve high sensitivity for detecting particles such as bacteria, viruses, aggregates, immuno-complexes, molecules, or ionic species. The device provides for affinity-based electrochemical detection of particles with single-particle sensitivity. The disclosed device and methods are based on microelectrodes with surface-attached, affinity ligands (e.g., antibodies, combinatorial peptides, glycolipids) that bind selectively to some target particle species. The electrodes electrolyze chemical species present in the particle-containing solution, and particle interaction with a sensor element modulates its electrolytic activity. The devices may be used individually, employed as sensors, used in arrays for a single specific type of particle or for a range of particle types, or configured into arrays of sensors having both these attributes.

Antenna array geometry optimization for a passive coherent localisation system

NASA Astrophysics Data System (ADS)

Knott, Peter; Kuschel, Heiner; O'Hagan, Daniel

2012-11-01

Passive Coherent Localisation (PCL), also known as Passive Radar, making use of RF sources of opportunity such as Radio or TV Broadcasting Stations, Cellular Phone Network Base Stations, etc. is an advancing technology for covert operation because no active radar transmitter is required. It is also an attractive addition to existing active radar stations because it has the potential to discover low-flying and low-observable targets. The CORA (Covert Radar) experimental passive radar system currently developed at Fraunhofer-FHR features a multi-channel digital radar receiver and a circular antenna array with separate elements for the VHF- and the UHF-range and is used to exploit alternatively Digital Audio (DAB) or Video Broadcasting (DVB-T) signals. For an extension of the system, a wideband antenna array is being designed for which a new discone antenna element has been developed covering the full DVB-T frequency range. The present paper describes the outline of the system and the numerical modelling and optimisation methods applied to solve the complex task of antenna array design: Electromagnetic full wave analysis is required for the parametric design of the antenna elements while combinatorial optimization methods are applied to find the best array positions and excitation coefficients for a regular omni-directional antenna performance. The different steps are combined in an iterative loop until the optimum array layout is found. Simulation and experimental results for the current system will be shown.

How the brain assigns a neural tag to arbitrary points in a high-dimensional space

NASA Astrophysics Data System (ADS)

Stevens, Charles

Brains in almost all organisms need to deal with very complex stimuli. For example, most mammals are very good at face recognition, and faces are very complex objects indeed. For example, modern face recognition software represents a face as a point in a 10,000 dimensional space. Every human must be able to learn to recognize any of the 7 billion faces in the world, and can recognize familiar faces after a display of the face is viewed for only a few hundred milliseconds. Because we do not understand how faces are assigned locations in a high-dimensional space by the brain, attacking the problem of how face recognition is accomplished is very difficult. But a much easier problem of the same sort can be studied for odor recognition. For the mouse, each odor is assigned a point in a 1000 dimensional space, and the fruit fly assigns any odor a location in only a 50 dimensional space. A fly has about 50 distinct types of odorant receptor neurons (ORNs), each of which produce nerve impulses at a specific rate for each different odor. This pattern of firing produced across 50 ORNs is called `a combinatorial odor code', and this code assigns every odor a point in a 50 dimensional space that is used to identify the odor. In order to learn the odor, the brain must alter the strength of synapses. The combinatorial code cannot itself by used to change synaptic strength because all odors use same neurons to form the code, and so all synapses would be changed for any odor and the odors could not be distinguished. In order to learn an odor, the brain must assign a set of neurons - the odor tag - that have the property that these neurons (1) should make use of all of the information available about the odor, and (2) insure that any two tags overlap as little as possible (so one odor does not modify synapses used by other odors). In the talk, I will explain how the olfactory system of both the fruit fly and the mouse produce a tag for each odor that has these two properties. Supported by NSF.

Ag-NP@Ge-nanotaper/Si-micropillar ordered arrays as ultrasensitive and uniform surface enhanced Raman scattering substrates.

PubMed

Liu, Jing; Meng, Guowen; Li, Zhongbo; Huang, Zhulin; Li, Xiangdong

2015-11-21

Surface-enhanced Raman scattering (SERS) is considered to be an excellent candidate for analytical detection schemes, because of its molecular specificity, rapid response and high sensitivity. Here, SERS-substrates of Ag-nanoparticle (Ag-NP) decorated Ge-nanotapers grafted on hexagonally ordered Si-micropillar (denoted as Ag-NP@Ge-nanotaper/Si-micropillar) arrays are fabricated via a combinatorial process of two-step etching to achieve hexagonal Si-micropillar arrays, chemical vapor deposition of flocky Ge-nanotapers on each Si-micropillar and decoration of Ag-NPs onto the Ge-nanotapers through galvanic displacement. With high density three-dimensional (3D) "hot spots" created from the large quantities of the neighboring Ag-NPs and large-scale uniform morphology, the hierarchical Ag-NP@Ge-nanotaper/Si-micropillar arrays exhibit strong and reproducible SERS activity. Using our hierarchical 3D SERS-substrates, both methyl parathion (a commonly used pesticide) and PCB-2 (one congener of highly toxic polychlorinated biphenyls) with concentrations down to 10(-7) M and 10(-5) M have been detected respectively, showing great potential in SERS-based rapid trace-level detection of toxic organic pollutants in the environment.

Molecular computational elements encode large populations of small objects

NASA Astrophysics Data System (ADS)

Prasanna de Silva, A.; James, Mark R.; McKinney, Bernadine O. F.; Pears, David A.; Weir, Sheenagh M.

2006-10-01

Since the introduction of molecular computation, experimental molecular computational elements have grown to encompass small-scale integration, arithmetic and games, among others. However, the need for a practical application has been pressing. Here we present molecular computational identification (MCID), a demonstration that molecular logic and computation can be applied to a widely relevant issue. Examples of populations that need encoding in the microscopic world are cells in diagnostics or beads in combinatorial chemistry (tags). Taking advantage of the small size (about 1nm) and large `on/off' output ratios of molecular logic gates and using the great variety of logic types, input chemical combinations, switching thresholds and even gate arrays in addition to colours, we produce unique identifiers for members of populations of small polymer beads (about 100μm) used for synthesis of combinatorial libraries. Many millions of distinguishable tags become available. This method should be extensible to far smaller objects, with the only requirement being a `wash and watch' protocol. Our focus on converting molecular science into technology concerning analog sensors, turns to digital logic devices in the present work.

Molecular computational elements encode large populations of small objects.

PubMed

de Silva, A Prasanna; James, Mark R; McKinney, Bernadine O F; Pears, David A; Weir, Sheenagh M

2006-10-01

Since the introduction of molecular computation, experimental molecular computational elements have grown to encompass small-scale integration, arithmetic and games, among others. However, the need for a practical application has been pressing. Here we present molecular computational identification (MCID), a demonstration that molecular logic and computation can be applied to a widely relevant issue. Examples of populations that need encoding in the microscopic world are cells in diagnostics or beads in combinatorial chemistry (tags). Taking advantage of the small size (about 1 nm) and large 'on/off' output ratios of molecular logic gates and using the great variety of logic types, input chemical combinations, switching thresholds and even gate arrays in addition to colours, we produce unique identifiers for members of populations of small polymer beads (about 100 microm) used for synthesis of combinatorial libraries. Many millions of distinguishable tags become available. This method should be extensible to far smaller objects, with the only requirement being a 'wash and watch' protocol. Our focus on converting molecular science into technology concerning analog sensors, turns to digital logic devices in the present work.

Using peptide array to identify binding motifs and interaction networks for modular domains.

PubMed

Li, Shawn S-C; Wu, Chenggang

2009-01-01

Specific protein-protein interactions underlie all essential biological processes and form the basis of cellular signal transduction. The recognition of a short, linear peptide sequence in one protein by a modular domain in another represents a common theme of macromolecular recognition in cells, and the importance of this mode of protein-protein interaction is highlighted by the large number of peptide-binding domains encoded by the human genome. This phenomenon also provides a unique opportunity to identify protein-protein binding events using peptide arrays and complementary biochemical assays. Accordingly, high-density peptide array has emerged as a useful tool by which to map domain-mediated protein-protein interaction networks at the proteome level. Using the Src-homology 2 (SH2) and 3 (SH3) domains as examples, we describe the application of oriented peptide array libraries in uncovering specific motifs recognized by an SH2 domain and the use of high-density peptide arrays in identifying interaction networks mediated by the SH3 domain. Methods reviewed here could also be applied to other modular domains, including catalytic domains, that recognize linear peptide sequences.

Immobilized OBOC combinatorial bead array to facilitate multiplicative screening.

PubMed

Xiao, Wenwu; Bononi, Fernanda C; Townsend, Jared; Li, Yuanpei; Liu, Ruiwu; Lam, Kit S

2013-07-01

One-bead-one-compound (OBOC) combinatorial library screening has been broadly utilized for the last two decades to identify small molecules, peptides or peptidomimetics targeting variable screening probes such as cell surface receptors, bacteria, protein kinases, phosphatases, proteases etc. In previous screening methods, library beads were suspended in solution and screened against one single probe. Only the positive beads were tracked and isolated for additional screens and finally selected for chemical decoding. During this process, the remaining negative beads were not tracked and discarded. Here we report a novel bead immobilization method such that a bead library array can be conveniently prepared and screened in its entirety, sequentially many times with a series of distinct probes. This method not only allows us to increase the screening efficiency but also permits us to determine the binding profile of each and every library bead against a large number of target receptors. As proof of concept, we serially screened a random OBOC disulfide containing cyclic heptapeptide library with three water soluble dyes as model probes: malachite green, bromocresol purple and indigo carmine. This multiplicative screening approach resulted in a rapid determination of the binding profile of each and every bead respective to each of the three dyes. Beads that interacted with malachite green only, bromocresol purple only, or both indigo carmine and bromocresol purple were isolated, and their peptide sequences were determined with microsequencer. Ultimately, the novel OBOC multiplicative screening approach could play a key role in the enhancement of existing on-bead assays such as whole cell binding, bacteria binding, protein binding, posttranslational modifications etc. with increased efficiency, capacity, and specificity.

Rapid recognition of volatile organic compounds with colorimetric sensor arrays for lung cancer screening.

PubMed

Zhong, Xianhua; Li, Dan; Du, Wei; Yan, Mengqiu; Wang, You; Huo, Danqun; Hou, Changjun

2018-06-01

Volatile organic compounds (VOCs) in breath can be used as biomarkers to identify early stages of lung cancer. Herein, we report a disposable colorimetric array that has been constructed from diverse chemo-responsive colorants. Distinguishable difference maps were plotted within 4 min for specifically targeted VOCs. Through the consideration of various chemical interactions with VOCs, the arrays successfully discriminate between 20 different volatile organic compounds in breath that are related to lung cancer. VOCs were identified either with the visualized difference maps or through pattern recognition with an accuracy of at least 90%. No uncertainties or errors were observed in the hierarchical cluster analysis (HCA). Finally, good reproducibility and stability of the array was achieved against changes in humidity. Generally, this work provides fundamental support for construction of simple and rapid VOC sensors. More importantly, this approach provides a hypothesis-free array method for breath testing via VOC profiling. Therefore, this small, rapid, non-invasive, inexpensive, and visualized sensor array is a powerful and promising tool for early screening of lung cancer. Graphical abstract A disposable colorimetric array has been developed with broadly chemo-responsive dyes to incorporate various chemical interactions, through which the arrays successfully discriminate 20 VOCs that are related to lung cancer via difference maps alone or chemometrics within 4 min. The hydrophobic porous matrix provides good stability against changes in humidity.

Simplified biased random walk model for RecA-protein-mediated homology recognition offers rapid and accurate self-assembly of long linear arrays of binding sites

NASA Astrophysics Data System (ADS)

Kates-Harbeck, Julian; Tilloy, Antoine; Prentiss, Mara

2013-07-01

Inspired by RecA-protein-based homology recognition, we consider the pairing of two long linear arrays of binding sites. We propose a fully reversible, physically realizable biased random walk model for rapid and accurate self-assembly due to the spontaneous pairing of matching binding sites, where the statistics of the searched sample are included. In the model, there are two bound conformations, and the free energy for each conformation is a weakly nonlinear function of the number of contiguous matched bound sites.

Molecularly Imprinted Sol-Gel-Based QCM Sensor Arrays for the Detection and Recognition of Volatile Aldehydes.

PubMed

Liu, Chuanjun; Wyszynski, Bartosz; Yatabe, Rui; Hayashi, Kenshi; Toko, Kiyoshi

2017-02-16

The detection and recognition of metabolically derived aldehydes, which have been identified as important products of oxidative stress and biomarkers of cancers; are considered as an effective approach for early cancer detection as well as health status monitoring. Quartz crystal microbalance (QCM) sensor arrays based on molecularly imprinted sol-gel (MISG) materials were developed in this work for highly sensitive detection and highly selective recognition of typical aldehyde vapors including hexanal (HAL); nonanal (NAL) and bezaldehyde (BAL). The MISGs were prepared by a sol-gel procedure using two matrix precursors: tetraethyl orthosilicate (TEOS) and tetrabutoxytitanium (TBOT). Aminopropyltriethoxysilane (APT); diethylaminopropyltrimethoxysilane (EAP) and trimethoxy-phenylsilane (TMP) were added as functional monomers to adjust the imprinting effect of the matrix. Hexanoic acid (HA); nonanoic acid (NA) and benzoic acid (BA) were used as psuedotemplates in view of their analogous structure to the target molecules as well as the strong hydrogen-bonding interaction with the matrix. Totally 13 types of MISGs with different components were prepared and coated on QCM electrodes by spin coating. Their sensing characters towards the three aldehyde vapors with different concentrations were investigated qualitatively. The results demonstrated that the response of individual sensors to each target strongly depended on the matrix precursors; functional monomers and template molecules. An optimization of the 13 MISG materials was carried out based on statistical analysis such as principle component analysis (PCA); multivariate analysis of covariance (MANCOVA) and hierarchical cluster analysis (HCA). The optimized sensor array consisting of five channels showed a high discrimination ability on the aldehyde vapors; which was confirmed by quantitative comparison with a randomly selected array. It was suggested that both the molecularly imprinting (MIP) effect and the matrix effect contributed to the sensitivity and selectivity of the optimized sensor array. The developed MISGs were expected to be promising materials for the detection and recognition of volatile aldehydes contained in exhaled breath or human body odor.

Molecularly Imprinted Sol-Gel-Based QCM Sensor Arrays for the Detection and Recognition of Volatile Aldehydes

PubMed Central

Liu, Chuanjun; Wyszynski, Bartosz; Yatabe, Rui; Hayashi, Kenshi; Toko, Kiyoshi

2017-01-01

The detection and recognition of metabolically derived aldehydes, which have been identified as important products of oxidative stress and biomarkers of cancers; are considered as an effective approach for early cancer detection as well as health status monitoring. Quartz crystal microbalance (QCM) sensor arrays based on molecularly imprinted sol-gel (MISG) materials were developed in this work for highly sensitive detection and highly selective recognition of typical aldehyde vapors including hexanal (HAL); nonanal (NAL) and bezaldehyde (BAL). The MISGs were prepared by a sol-gel procedure using two matrix precursors: tetraethyl orthosilicate (TEOS) and tetrabutoxytitanium (TBOT). Aminopropyltriethoxysilane (APT); diethylaminopropyltrimethoxysilane (EAP) and trimethoxy-phenylsilane (TMP) were added as functional monomers to adjust the imprinting effect of the matrix. Hexanoic acid (HA); nonanoic acid (NA) and benzoic acid (BA) were used as psuedotemplates in view of their analogous structure to the target molecules as well as the strong hydrogen-bonding interaction with the matrix. Totally 13 types of MISGs with different components were prepared and coated on QCM electrodes by spin coating. Their sensing characters towards the three aldehyde vapors with different concentrations were investigated qualitatively. The results demonstrated that the response of individual sensors to each target strongly depended on the matrix precursors; functional monomers and template molecules. An optimization of the 13 MISG materials was carried out based on statistical analysis such as principle component analysis (PCA); multivariate analysis of covariance (MANCOVA) and hierarchical cluster analysis (HCA). The optimized sensor array consisting of five channels showed a high discrimination ability on the aldehyde vapors; which was confirmed by quantitative comparison with a randomly selected array. It was suggested that both the molecularly imprinting (MIP) effect and the matrix effect contributed to the sensitivity and selectivity of the optimized sensor array. The developed MISGs were expected to be promising materials for the detection and recognition of volatile aldehydes contained in exhaled breath or human body odor. PMID:28212347

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

ERIC Educational Resources Information Center

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…

Colorful solar selective absorber integrated with different colored units.

PubMed

Chen, Feiliang; Wang, Shao-Wei; Liu, Xingxing; Ji, Ruonan; Li, Zhifeng; Chen, Xiaoshuang; Chen, Yuwei; Lu, Wei

2016-01-25

Solar selective absorbers are the core part for solar thermal technologies such as solar water heaters, concentrated solar power, solar thermoelectric generators and solar thermophotovoltaics. Colorful solar selective absorber can provide new freedom and flexibility beyond energy performance, which will lead to wider utilization of solar technologies. In this work, we present a monolithic integration of colored solar absorber array with different colors on a single substrate based on a multilayered structure of Cu/TiN(x)O(y)/TiO(2)/Si(3)N(4)/SiO(2). A colored solar absorber array with 16 color units is demonstrated experimentally by using combinatorial deposition technique via changing the thickness of SiO(2) layer. The solar absorptivity and thermal emissivity of all the color units is higher than 92% and lower than 5.5%, respectively. The colored solar selective absorber array can have colorful appearance and designable patterns while keeping high energy performance at the same time. It is a new candidate for a number of solar applications, especially for architecture integration and military camouflage.

Binary zone-plate array for a parallel joint transform correlator applied to face recognition.

PubMed

Kodate, K; Hashimoto, A; Thapliya, R

1999-05-10

Taking advantage of small aberrations, high efficiency, and compactness, we developed a new, to our knowledge, design procedure for a binary zone-plate array (BZPA) and applied it to a parallel joint transform correlator for the recognition of the human face. Pairs of reference and unknown images of faces are displayed on a liquid-crystal spatial light modulator (SLM), Fourier transformed by the BZPA, intensity recorded on an optically addressable SLM, and inversely Fourier transformed to obtain correlation signals. Consideration of the bandwidth allows the relations among the channel number, the numerical aperture of the zone plates, and the pattern size to be determined. Experimentally a five-channel parallel correlator was implemented and tested successfully with a 100-person database. The design and the fabrication of a 20-channel BZPA for phonetic character recognition are also included.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yulaev, Alexander; Guo, Hongxuan; Strelcov, Evgheni

Atomic-scale thickness, molecular impermeability, low atomic number, and mechanical strength make graphene an ideal electron-transparent membrane for material characterization in liquids and gases with scanning electron microscopy and spectroscopy. Here in this paper, we present a novel sample platform made of an array of thousands of identical isolated graphene-capped microchannels with high aspect ratio. A combination of a global wide field of view with high resolution local imaging of the array allows for high throughput in situ studies as well as for combinatorial screening of solutions, liquid interfaces, and immersed samples. We demonstrate the capabilities of this platform by studyingmore » a pure water sample in comparison with alkali halide solutions, a model electrochemical plating process, and beam-induced crystal growth in liquid electrolyte. Spectroscopic characterization of liquid interfaces and immersed objects with Auger and X-ray fluorescence analysis through the graphene membrane are also demonstrated.« less

Combinatorial Libraries of Arrayable Single-Chain Antibodies

NASA Astrophysics Data System (ADS)

Benhar, Itai

Antibodies that bind their respective targets with high affinity and specificity have proven to be essential reagents for biological research. Antibody phage display has become the leading tool for the rapid isolation of single-chain variable fragment (scFv) antibodies in vitro for research applications, but there is usually a gap between scFv isolation and its application in an array format suitable for high-throughput proteomics. In this chapter, we present our antibody phage display system where antibody isolation and scFv immobilization are facilitated by the design of the phagemid vector used as platform. In our system, the scFvs are fused at their C-termini to a cellulose-binding domain (CBD) and can be immobilized onto cellulose-based filters. This made it possible to develop a unique filter lift screen that allowed the efficient screen for multiple binding specificities, and to directly apply library-derived scFvs in an antibody spotted microarray.

Whole organism lineage tracing by combinatorial and cumulative genome editing

PubMed Central

McKenna, Aaron; Findlay, Gregory M.; Gagnon, James A.; Horwitz, Marshall S.; Schier, Alexander F.; Shendure, Jay

2016-01-01

Multicellular systems develop from single cells through distinct lineages. However, current lineage tracing approaches scale poorly to whole, complex organisms. Here we use genome editing to progressively introduce and accumulate diverse mutations in a DNA barcode over multiple rounds of cell division. The barcode, an array of CRISPR/Cas9 target sites, marks cells and enables the elucidation of lineage relationships via the patterns of mutations shared between cells. In cell culture and zebrafish, we show that rates and patterns of editing are tunable, and that thousands of lineage-informative barcode alleles can be generated. By sampling hundreds of thousands of cells from individual zebrafish, we find that most cells in adult organs derive from relatively few embryonic progenitors. In future analyses, genome editing of synthetic target arrays for lineage tracing (GESTALT) can be used to generate large-scale maps of cell lineage in multicellular systems for normal development and disease. PMID:27229144

Optimizing an Actuator Array for the Control of Multi-Frequency Noise in Aircraft Interiors

NASA Technical Reports Server (NTRS)

Palumbo, D. L.; Padula, S. L.

1997-01-01

Techniques developed for selecting an optimized actuator array for interior noise reduction at a single frequency are extended to the multi-frequency case. Transfer functions for 64 actuators were obtained at 5 frequencies from ground testing the rear section of a fully trimmed DC-9 fuselage. A single loudspeaker facing the left side of the aircraft was the primary source. A combinatorial search procedure (tabu search) was employed to find optimum actuator subsets of from 2 to 16 actuators. Noise reduction predictions derived from the transfer functions were used as a basis for evaluating actuator subsets during optimization. Results indicate that it is necessary to constrain actuator forces during optimization. Unconstrained optimizations selected actuators which require unrealistically large forces. Two methods of constraint are evaluated. It is shown that a fast, but approximate, method yields results equivalent to an accurate, but computationally expensive, method.

Discovery of Peptidomimetic Ligands of EED as Allosteric Inhibitors of PRC2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barnash, Kimberly D.; The, Juliana; Norris-Drouin, Jacqueline L.

The function of EED within polycomb repressive complex 2 (PRC2) is mediated by a complex network of protein–protein interactions. Allosteric activation of PRC2 by binding of methylated proteins to the embryonic ectoderm development (EED) aromatic cage is essential for full catalytic activity, but details of this regulation are not fully understood. EED’s recognition of the product of PRC2 activity, histone H3 lysine 27 trimethylation (H3K27me3), stimulates PRC2 methyltransferase activity at adjacent nucleosomes leading to H3K27me3 propagation and, ultimately, gene repression. By coupling combinatorial chemistry and structure-based design, we optimized a low-affinity methylated jumonji, AT-rich interactive domain 2 (Jarid2) peptide tomore » a smaller, more potent peptidomimetic ligand (K d = 1.14 ± 0.14 μM) of the aromatic cage of EED. Our strategy illustrates the effectiveness of applying combinatorial chemistry to achieve both ligand potency and property optimization. Furthermore, the resulting ligands, UNC5114 and UNC5115, demonstrate that targeted disruption of EED’s reader function can lead to allosteric inhibition of PRC2 catalytic activity.« less

Directional harmonic theory: a computational Gestalt model to account for illusory contour and vertex formation.

PubMed

Lehar, Steven

2003-01-01

Visual illusions and perceptual grouping phenomena offer an invaluable tool for probing the computational mechanism of low-level visual processing. Some illusions, like the Kanizsa figure, reveal illusory contours that form edges collinear with the inducing stimulus. This kind of illusory contour has been modeled by neural network models by way of cells equipped with elongated spatial receptive fields designed to detect and complete the collinear alignment. There are, however, other illusory groupings which are not so easy to account for in neural network terms. The Ehrenstein illusion exhibits an illusory contour that forms a contour orthogonal to the stimulus instead of collinear with it. Other perceptual grouping effects reveal illusory contours that exhibit a sharp corner or vertex, and still others take the form of vertices defined by the intersection of three, four, or more illusory contours that meet at a point. A direct extension of the collinear completion models to account for these phenomena tends towards a combinatorial explosion, because it would suggest cells with specialized receptive fields configured to perform each of those completion types, each of which would have to be replicated at every location and every orientation across the visual field. These phenomena therefore challenge the adequacy of the neural network approach to account for these diverse perceptual phenomena. I have proposed elsewhere an alternative paradigm of neurocomputation in the harmonic resonance theory (Lehar 1999, see website), whereby pattern recognition and completion are performed by spatial standing waves across the neural substrate. The standing waves perform a computational function analogous to that of the spatial receptive fields of the neural network approach, except that, unlike that paradigm, a single resonance mechanism performs a function equivalent to a whole array of spatial receptive fields of different spatial configurations and of different orientations, and thereby avoids the combinatorial explosion inherent in the older paradigm. The present paper presents the directional harmonic model, a more specific development of the harmonic resonance theory, designed to account for specific perceptual grouping phenomena. Computer simulations of the directional harmonic model show that it can account for collinear contours as observed in the Kanizsa figure, orthogonal contours as seen in the Ehrenstein illusion, and a number of illusory vertex percepts composed of two, three, or more illusory contours that meet in a variety of configurations.

Recognition of the epicardial breakthrough on body surface isopotential maps: influence of the inter-electrode distance on the patterns reflecting the epicardial breakthrough.

PubMed

Toyama, J; Tabata, O

1981-10-01

The epicardial breakthrough can be recognized from the localized depression of the body surface potential, which is characterized by a localized bend of the equipotential lines or a send-minimum on isopotential maps. Recognition of epicardial breakthrough with isopotential maps enables us to diagnose location of the block site of the bundle branch blocks more precisely than by ECG or VCG. However, the optimum inter-electrode distance for detection of such a localized potential has not been determined. In the present study, influence of the inter-electrode distance on the characteristic patterns reflecting the epicardial breakthrough was studied on 16 healthy persons using 9 x 9 electrode arrays with inter-electrode distance of 1.25 cm, 5 x 5 with 2.5 cm, and 3 x 3 with 5 cm. Breakthrough was recognized in 15 out of 16 cases (94%) on maps recorded with electrode arrays with inter-electrode distance of 1.25 and 2.5 cm. However, detectability of the breakthrough was reduced to 10 out of 16 cases (63%) with electrode array having inter-electrode distance of 5 cm. In conclusion, it is preferable to use an electrode array with an inter-electrode distance of no more than 2.5 cm for the purpose of breakthrough recognition.

Current state and future prospects of immunotherapy for glioma.

PubMed

Kamran, Neha; Alghamri, Mahmoud S; Nunez, Felipe J; Shah, Diana; Asad, Antonela S; Candolfi, Marianela; Altshuler, David; Lowenstein, Pedro R; Castro, Maria G

2018-02-01

There is a large unmet need for effective therapeutic approaches for glioma, the most malignant brain tumor. Clinical and preclinical studies have enormously expanded our knowledge about the molecular aspects of this deadly disease and its interaction with the host immune system. In this review we highlight the wide array of immunotherapeutic interventions that are currently being tested in glioma patients. Given the molecular heterogeneity, tumor immunoediting and the profound immunosuppression that characterize glioma, it has become clear that combinatorial approaches targeting multiple pathways tailored to the genetic signature of the tumor will be required in order to achieve optimal therapeutic efficacy.

A Novel Receptor-Like Kinase Involved in Fungal Pathogen Defense in Arabidopsis thaliana

USDA-ARS?s Scientific Manuscript database

Plants are under constant attack from a variety of disease causing organisms. Lacking an adaptive immune system, plants repel pathogen attack via an array of pathogen recognition machinery. Receptor-like kinases (RLKs) are involved in the recognition of pathogen-associated molecular patterns (PAMPs)...

Pattern Recognition by Retina-Like Devices.

ERIC Educational Resources Information Center

Weiman, Carl F. R.; Rothstein, Jerome

This study has investigated some pattern recognition capabilities of devices consisting of arrays of cooperating elements acting in parallel. The problem of recognizing straight lines in general position on the quadratic lattice has been completely solved by applying parallel acting algorithms to a special code for lines on the lattice. The…

A Strategic Design of an Opto-Chemical Security Device with Resettable and Reconfigurable Password Based Upon Dual Channel Two-in-One Chemosensor Molecule.

PubMed

Majumdar, Tapas; Haldar, Basudeb; Mallick, Arabinda

2017-02-20

A simple strategy is proposed to design and develop an intelligent device based on dual channel ion responsive spectral properties of a commercially available molecule, harmine (HM). The system can process different sets of opto-chemical inputs generating different patterns as fluorescence outputs at specific wavelengths which can provide an additional level of protection exploiting both password and pattern recognitions. The proposed system could have the potential to come up with highly secured combinatorial locks at the molecular level that could pose valuable real time and on-site applications for user authentication.

A Strategic Design of an Opto-Chemical Security Device with Resettable and Reconfigurable Password Based Upon Dual Channel Two-in-One Chemosensor Molecule

NASA Astrophysics Data System (ADS)

Majumdar, Tapas; Haldar, Basudeb; Mallick, Arabinda

2017-02-01

A simple strategy is proposed to design and develop an intelligent device based on dual channel ion responsive spectral properties of a commercially available molecule, harmine (HM). The system can process different sets of opto-chemical inputs generating different patterns as fluorescence outputs at specific wavelengths which can provide an additional level of protection exploiting both password and pattern recognitions. The proposed system could have the potential to come up with highly secured combinatorial locks at the molecular level that could pose valuable real time and on-site applications for user authentication.

Polarimetric Imaging System for Automatic Target Detection and Recognition

DTIC Science & Technology

2000-03-01

technique shown in Figure 4(b) can also be used to integrate polarizer arrays with other types of imaging sensors, such as LWIR cameras and uncooled...vertical stripe pattern in this φ image is caused by nonuniformities in the particular polarizer array used. 2. CIRCULAR POLARIZATION IMAGING USING

Recognition Time for Letters and Nonletters: Effects of Serial Position, Array Size, and Processing Order.

ERIC Educational Resources Information Center

Mason, Mildred

1982-01-01

Three experiments report additional evidence that it is a mistake to account for all interletter effects solely in terms of sensory variables. These experiments attest to the importance of structural variables such as retina location, array size, and ordinal position. (Author/PN)

Drosophila Nanos acts as a molecular clamp that modulates the RNA-binding and repression activities of Pumilio.

PubMed

Weidmann, Chase A; Qiu, Chen; Arvola, René M; Lou, Tzu-Fang; Killingsworth, Jordan; Campbell, Zachary T; Tanaka Hall, Traci M; Goldstrohm, Aaron C

2016-08-02

Collaboration among the multitude of RNA-binding proteins (RBPs) is ubiquitous, yet our understanding of these key regulatory complexes has been limited to single RBPs. We investigated combinatorial translational regulation by Drosophila Pumilio (Pum) and Nanos (Nos), which control development, fertility, and neuronal functions. Our results show how the specificity of one RBP (Pum) is modulated by cooperative RNA recognition with a second RBP (Nos) to synergistically repress mRNAs. Crystal structures of Nos-Pum-RNA complexes reveal that Nos embraces Pum and RNA, contributes sequence-specific contacts, and increases Pum RNA-binding affinity. Nos shifts the recognition sequence and promotes repression complex formation on mRNAs that are not stably bound by Pum alone, explaining the preponderance of sub-optimal Pum sites regulated in vivo. Our results illuminate the molecular mechanism of a regulatory switch controlling crucial gene expression programs, and provide a framework for understanding how the partnering of RBPs evokes changes in binding specificity that underlie regulatory network dynamics.

Drosophila Nanos acts as a molecular clamp that modulates the RNA-binding and repression activities of Pumilio

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weidmann, Chase A.; Qiu, Chen; Arvola, René M.

Collaboration among the multitude of RNA-binding proteins (RBPs) is ubiquitous, yet our understanding of these key regulatory complexes has been limited to single RBPs. We investigated combinatorial translational regulation byDrosophilaPumilio (Pum) and Nanos (Nos), which control development, fertility, and neuronal functions. Our results show how the specificity of one RBP (Pum) is modulated by cooperative RNA recognition with a second RBP (Nos) to synergistically repress mRNAs. Crystal structures of Nos-Pum-RNA complexes reveal that Nos embraces Pum and RNA, contributes sequence-specific contacts, and increases Pum RNA-binding affinity. Nos shifts the recognition sequence and promotes repression complex formation on mRNAs that aremore » not stably bound by Pum alone, explaining the preponderance of sub-optimal Pum sites regulatedin vivo. Our results illuminate the molecular mechanism of a regulatory switch controlling crucial gene expression programs, and provide a framework for understanding how the partnering of RBPs evokes changes in binding specificity that underlie regulatory network dynamics.« less

Digital and optical shape representation and pattern recognition; Proceedings of the Meeting, Orlando, FL, Apr. 4-6, 1988

NASA Technical Reports Server (NTRS)

Juday, Richard D. (Editor)

1988-01-01

The present conference discusses topics in pattern-recognition correlator architectures, digital stereo systems, geometric image transformations and their applications, topics in pattern recognition, filter algorithms, object detection and classification, shape representation techniques, and model-based object recognition methods. Attention is given to edge-enhancement preprocessing using liquid crystal TVs, massively-parallel optical data base management, three-dimensional sensing with polar exponential sensor arrays, the optical processing of imaging spectrometer data, hybrid associative memories and metric data models, the representation of shape primitives in neural networks, and the Monte Carlo estimation of moment invariants for pattern recognition.

An electronic nose for quantitative determination of gas concentrations

NASA Astrophysics Data System (ADS)

Jasinski, Grzegorz; Kalinowski, Paweł; Woźniak, Łukasz

2016-11-01

The practical application of human nose for fragrance recognition is severely limited by the fact that our sense of smell is subjective and gets tired easily. Consequently, there is considerable need for an instrument that can be a substitution of the human sense of smell. Electronic nose devices from the mid 1980s are used in growing number of applications. They comprise an array of several electrochemical gas sensors with partial specificity and a pattern recognition algorithms. Most of such systems, however, is only used for qualitative measurements. In this article usage of such system in quantitative determination of gas concentration is demonstrated. Electronic nose consist of a sensor array with eight commercially available Taguchi type gas sensor. Performance of three different pattern recognition algorithms is compared, namely artificial neural network, partial least squares regression and support vector machine regression. The electronic nose is used for ammonia and nitrogen dioxide concentration determination.

A neural approach for improving the measurement capability of an electronic nose

NASA Astrophysics Data System (ADS)

Chimenti, M.; DeRossi, D.; Di Francesco, F.; Domenici, C.; Pieri, G.; Pioggia, G.; Salvetti, O.

2003-06-01

Electronic noses, instruments for automatic recognition of odours, are typically composed of an array of partially selective sensors, a sampling system, a data acquisition device and a data processing system. For the purpose of evaluating the quality of olive oil, an electronic nose based on an array of conducting polymer sensors capable of discriminating olive oil aromas was developed. The selection of suitable pattern recognition techniques for a particular application can enhance the performance of electronic noses. Therefore, an advanced neural recognition algorithm for improving the measurement capability of the device was designed and implemented. This method combines multivariate statistical analysis and a hierarchical neural-network architecture based on self-organizing maps and error back-propagation. The complete system was tested using samples composed of characteristic olive oil aromatic components in refined olive oil. The results obtained have shown that this approach is effective in grouping aromas into different categories representative of their chemical structure.

The disadvantage of combinatorial communication.

PubMed Central

Lachmann, Michael; Bergstrom, Carl T.

2004-01-01

Combinatorial communication allows rapid and efficient transfer of detailed information, yet combinatorial communication is used by few, if any, non-human species. To complement recent studies illustrating the advantages of combinatorial communication, we highlight a critical disadvantage. We use the concept of information value to show that deception poses a greater and qualitatively different threat to combinatorial signalling than to non-combinatorial systems. This additional potential for deception may represent a strategic barrier that has prevented widespread evolution of combinatorial communication. Our approach has the additional benefit of drawing clear distinctions among several types of deception that can occur in communication systems. PMID:15556886

The disadvantage of combinatorial communication.

PubMed

Lachmann, Michael; Bergstrom, Carl T

2004-11-22

Combinatorial communication allows rapid and efficient transfer of detailed information, yet combinatorial communication is used by few, if any, non-human species. To complement recent studies illustrating the advantages of combinatorial communication, we highlight a critical disadvantage. We use the concept of information value to show that deception poses a greater and qualitatively different threat to combinatorial signalling than to non-combinatorial systems. This additional potential for deception may represent a strategic barrier that has prevented widespread evolution of combinatorial communication. Our approach has the additional benefit of drawing clear distinctions among several types of deception that can occur in communication systems.

View Combination: A Generalization Mechanism for Visual Recognition

ERIC Educational Resources Information Center

Friedman, Alinda; Waller, David; Thrash, Tyler; Greenauer, Nathan; Hodgson, Eric

2011-01-01

We examined whether view combination mechanisms shown to underlie object and scene recognition can integrate visual information across views that have little or no three-dimensional information at either the object or scene level. In three experiments, people learned four "views" of a two dimensional visual array derived from a three-dimensional…

Least Squares Neural Network-Based Wireless E-Nose System Using an SnO₂ Sensor Array.

PubMed

Shahid, Areej; Choi, Jong-Hyeok; Rana, Abu Ul Hassan Sarwar; Kim, Hyun-Seok

2018-05-06

Over the last few decades, the development of the electronic nose (E-nose) for detection and quantification of dangerous and odorless gases, such as methane (CH₄) and carbon monoxide (CO), using an array of SnO₂ gas sensors has attracted considerable attention. This paper addresses sensor cross sensitivity by developing a classifier and estimator using an artificial neural network (ANN) and least squares regression (LSR), respectively. Initially, the ANN was implemented using a feedforward pattern recognition algorithm to learn the collective behavior of an array as the signature of a particular gas. In the second phase, the classified gas was quantified by minimizing the mean square error using LSR. The combined approach produced 98.7% recognition probability, with 95.5 and 94.4% estimated gas concentration accuracies for CH₄ and CO, respectively. The classifier and estimator parameters were deployed in a remote microcontroller for the actualization of a wireless E-nose system.

On the Temporal Stability of Analyte Recognition with an E-Nose Based on a Metal Oxide Sensor Array in Practical Applications.

PubMed

Kiselev, Ilia; Sysoev, Victor; Kaikov, Igor; Koronczi, Ilona; Adil Akai Tegin, Ruslan; Smanalieva, Jamila; Sommer, Martin; Ilicali, Coskan; Hauptmannl, Michael

2018-02-11

The paper deals with a functional instability of electronic nose (e-nose) units which significantly limits their real-life applications. Here we demonstrate how to approach this issue with example of an e-nose based on a metal oxide sensor array developed at the Karlsruhe Institute of Technology (Germany). We consider the instability of e-nose operation at different time scales ranging from minutes to many years. To test the e-nose we employ open-air and headspace sampling of analyte odors. The multivariate recognition algorithm to process the multisensor array signals is based on the linear discriminant analysis method. Accounting for the received results, we argue that the stability of device operation is mostly affected by accidental changes in the ambient air composition. To overcome instabilities, we introduce the add-training procedure which is found to successfully manage both the temporal changes of ambient and the drift of multisensor array properties, even long-term. The method can be easily implemented in practical applications of e-noses and improve prospects for device marketing.

Molecularly imprinted polymer based microtiter chemiluminescence array for determination of phenothiazines and benzodiazepines in pork.

PubMed

Xia, Wan Qiu; Huang, Jun; Wang, Geng Nan; Liu, Jing; Wang, Jian Ping

2018-05-25

In this study, a molecularly imprinted polymer based chemiluminescence array capable of simultaneous determining phenothiazines and benzodiazepines was first reported. Two polymers were coated in different wells of the conventional 96-well microtiter plate as the recognition reagents, and the added analytes competed with a horseradish peroxidase-labeled bi-hapten conjugate to bind the recognition reagents. The light signal was induced by using a highly effective luminol-H 2 O 2 -IMP system. The assay procedure consisted of only one sample-loading step prior to data acquisition. Then, the array was used to determine 4 phenothiazines and 5 benzodiazepines in pork simultaneously. The limits of detection for the 9 drugs were in a range of 0.001-0.01 ng/mL, and the recoveries from the fortified blank pork were in a range of 63.5%-94.1%. Furthermore, the array could be reused for 8 times. The detection results for some real pork samples were consistent with an ultra performance liquid chromatography method. Copyright © 2018 Elsevier Inc. All rights reserved.

On the Temporal Stability of Analyte Recognition with an E-Nose Based on a Metal Oxide Sensor Array in Practical Applications

PubMed Central

Kaikov, Igor; Koronczi, Ilona; Adil Akai Tegin, Ruslan; Smanalieva, Jamila; Sommer, Martin; Ilicali, Coskan; Hauptmannl, Michael

2018-01-01

The paper deals with a functional instability of electronic nose (e-nose) units which significantly limits their real-life applications. Here we demonstrate how to approach this issue with example of an e-nose based on a metal oxide sensor array developed at the Karlsruhe Institute of Technology (Germany). We consider the instability of e-nose operation at different time scales ranging from minutes to many years. To test the e-nose we employ open-air and headspace sampling of analyte odors. The multivariate recognition algorithm to process the multisensor array signals is based on the linear discriminant analysis method. Accounting for the received results, we argue that the stability of device operation is mostly affected by accidental changes in the ambient air composition. To overcome instabilities, we introduce the add-training procedure which is found to successfully manage both the temporal changes of ambient and the drift of multisensor array properties, even long-term. The method can be easily implemented in practical applications of e-noses and improve prospects for device marketing. PMID:29439468

A facial expression of pax: Assessing children's "recognition" of emotion from faces.

PubMed

Nelson, Nicole L; Russell, James A

2016-01-01

In a classic study, children were shown an array of facial expressions and asked to choose the person who expressed a specific emotion. Children were later asked to name the emotion in the face with any label they wanted. Subsequent research often relied on the same two tasks--choice from array and free labeling--to support the conclusion that children recognize basic emotions from facial expressions. Here five studies (N=120, 2- to 10-year-olds) showed that these two tasks produce illusory recognition; a novel nonsense facial expression was included in the array. Children "recognized" a nonsense emotion (pax or tolen) and two familiar emotions (fear and jealousy) from the same nonsense face. Children likely used a process of elimination; they paired the unknown facial expression with a label given in the choice-from-array task and, after just two trials, freely labeled the new facial expression with the new label. These data indicate that past studies using this method may have overestimated children's expression knowledge. Copyright © 2015 Elsevier Inc. All rights reserved.

Proposed biomimetic molecular sensor array for astrobiology applications

NASA Astrophysics Data System (ADS)

Cullen, D. C.; Grant, W. D.; Piletsky, S.; Sims, M. R.

2001-08-01

A key objective of future astrobiology lander missions, e.g. to Mars and Europa, is the detection of biomarkers - molecules whose presence indicates the existence of either current or extinct life. To address limitations of current analytical methods for biomarker detection, we describe the methodology of a new project for demonstration of a robust molecular-recognition sensor array for astrobiology biomarkers. The sensor array will be realised by assembling components that have been demonstrated individually in previous or current research projects. The major components are (1) robust artificial molecular receptors comprised of molecular imprinted polymer (MIP) recognition systems and (2) a sensor array comprised of both optical and electrochemical sensor elements. These components will be integrated together using ink-jet printing technology coupled with in situ photo-polymerisation of MIPs. For demonstration, four model biomarkers are chosen as targets and represent various classes of potential biomarkers. Objectives of the proposed work include (1) demonstration of practical proof-of-concept, (2) identify areas for further development and (3) provide performance and design data for follow-up projects leading to astrobiology missions.

Why is combinatorial communication rare in the natural world, and why is language an exception to this trend?

PubMed

Scott-Phillips, Thomas C; Blythe, Richard A

2013-11-06

In a combinatorial communication system, some signals consist of the combinations of other signals. Such systems are more efficient than equivalent, non-combinatorial systems, yet despite this they are rare in nature. Why? Previous explanations have focused on the adaptive limits of combinatorial communication, or on its purported cognitive difficulties, but neither of these explains the full distribution of combinatorial communication in the natural world. Here, we present a nonlinear dynamical model of the emergence of combinatorial communication that, unlike previous models, considers how initially non-communicative behaviour evolves to take on a communicative function. We derive three basic principles about the emergence of combinatorial communication. We hence show that the interdependence of signals and responses places significant constraints on the historical pathways by which combinatorial signals might emerge, to the extent that anything other than the most simple form of combinatorial communication is extremely unlikely. We also argue that these constraints can be bypassed if individuals have the socio-cognitive capacity to engage in ostensive communication. Humans, but probably no other species, have this ability. This may explain why language, which is massively combinatorial, is such an extreme exception to nature's general trend for non-combinatorial communication.

Programming Recognition Arrays through Double Chalcogen-Bonding Interactions.

PubMed

Biot, Nicolas; Bonifazi, Davide

2018-04-11

In this work, we have programmed and synthesized a recognition motif constructed around a chalcogenazolo-pyridine scaffold (CGP) that, through the formation of frontal double chalcogen-bonding interactions, associates into dimeric EX-type complexes. The reliability of the double chalcogen-bonding interaction has been shown at the solid-state by X-ray analysis, depicting the strongest recognition persistence for a Te-congener. The high recognition fidelity, chemical and thermal stability and easy derivatization at the 2-position makes CGP a convenient motif for constructing supramolecular architectures through programmed chalcogen-bonding interactions. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Classification of 2-dimensional array patterns: assembling many small neural networks is better than using a large one.

PubMed

Chen, Liang; Xue, Wei; Tokuda, Naoyuki

2010-08-01

In many pattern classification/recognition applications of artificial neural networks, an object to be classified is represented by a fixed sized 2-dimensional array of uniform type, which corresponds to the cells of a 2-dimensional grid of the same size. A general neural network structure, called an undistricted neural network, which takes all the elements in the array as inputs could be used for problems such as these. However, a districted neural network can be used to reduce the training complexity. A districted neural network usually consists of two levels of sub-neural networks. Each of the lower level neural networks, called a regional sub-neural network, takes the elements in a region of the array as its inputs and is expected to output a temporary class label, called an individual opinion, based on the partial information of the entire array. The higher level neural network, called an assembling sub-neural network, uses the outputs (opinions) of regional sub-neural networks as inputs, and by consensus derives the label decision for the object. Each of the sub-neural networks can be trained separately and thus the training is less expensive. The regional sub-neural networks can be trained and performed in parallel and independently, therefore a high speed can be achieved. We prove theoretically in this paper, using a simple model, that a districted neural network is actually more stable than an undistricted neural network in noisy environments. We conjecture that the result is valid for all neural networks. This theory is verified by experiments involving gender classification and human face recognition. We conclude that a districted neural network is highly recommended for neural network applications in recognition or classification of 2-dimensional array patterns in highly noisy environments. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Array of Chemosensitive Resistors with Composites of Gas Chromatography (GC) Materials and Carbon Black for Detection and Recognition of VOCs: A Basic Study

PubMed Central

Wyszynski, Bartosz; Yatabe, Rui; Nakao, Atsuo; Nakatani, Masaya; Oki, Akio; Oka, Hiroaki; Toko, Kiyoshi

2017-01-01

Mimicking the biological olfaction, large odor-sensor arrays can be used to acquire a broad range of chemical information, with a potentially high degree of redundancy, to allow for enhanced control over the sensitivity and selectivity of artificial olfaction systems. The arrays should consist of the largest possible number of individual sensing elements while being miniaturized. Chemosensitive resistors are one of the sensing platforms that have a potential to satisfy these two conditions. In this work we test viability of fabricating a 16-element chemosensitive resistor array for detection and recognition of volatile organic compounds (VOCs). The sensors were fabricated using blends of carbon black and gas chromatography (GC) stationary-phase materials preselected based on their sorption properties. Blends of the selected GC materials with carbon black particles were subsequently coated over chemosensitive resistor devices and the resulting sensors/arrays evaluated in exposure experiments against vapors of pyrrole, benzenal, nonanal, and 2-phenethylamine at 150, 300, 450, and 900 ppb. Responses of the fabricated 16-element array were stable and differed for each individual odorant sample, proving the blends of GC materials with carbon black particles can be effectively used for fabrication of large odor-sensing arrays based on chemosensitive resistors. The obtained results suggest that the proposed sensing devices could be effective in discriminating odor/vapor samples at the sub-ppm level. PMID:28696353

Case Studies in e-RPL and e-PR

ERIC Educational Resources Information Center

Cameron, Roslyn; Miller, Allison

2014-01-01

The use of ePortfolios for recognition of prior learning (e-RPL) and for professional recognition (e-PR) is slowly gaining in popularity in the VET sector however their use is sporadic across educational sectors, disciplines, educational institutions and professions. Added to this is an array of purposes and types of e-RPL and e-PR models and…

The Roles of Tonal and Segmental Information in Mandarin Spoken Word Recognition: An Eyetracking Study

ERIC Educational Resources Information Center

Malins, Jeffrey G.; Joanisse, Marc F.

2010-01-01

We used eyetracking to examine how tonal versus segmental information influence spoken word recognition in Mandarin Chinese. Participants heard an auditory word and were required to identify its corresponding picture from an array that included the target item ("chuang2" "bed"), a phonological competitor (segmental: chuang1 "window"; cohort:…

Organic vapor discrimination with chemiresistor arrays of temperature modulated tin-oxide nanowires and thiolate-monolayer-protected gold nanoparticles.

PubMed

Scholten, K; Bohrer, F I; Dattoli, E; Lu, W; Zellers, E T

2011-03-25

This paper explores the discrimination of organic vapors with arrays of chemiresistors (CRs) employing interface layers of tin-oxide nanowires (NWs) and thiolate-monolayer-protected gold nanoparticles (MPNs). The former devices use contact-printed mats of NWs on micro-hotplate membranes to bridge a pair of metal electrodes. Oxidation at the NW surface causes changes in charge transport, the temperature dependence of which differs among different vapors, permitting vapor discrimination. The latter devices use solvent cast films of MPNs on interdigital electrodes operated at room temperature. Sorption into the organic monolayers causes changes in film tunneling resistance that differ among different vapors and MPN structures, permitting vapor discrimination. Here, we compare the performance and assess the 'complementarity' of these two types of sensors. Calibrated responses from an NW CR operated at two different temperatures and from a set of four different MPN CRs were generated for three test vapors: n-hexane, toluene, and nitromethane. This pooled data set was then analyzed using principal components regression classification models with varying degrees of random error superimposed on the responses via Monte Carlo simulation in order to estimate the rates of recognition/discrimination for arrays comprising different combinations of sensors. Results indicate that the diversity of most of the dual MPN-CR arrays exceeds that of the dual NW-CR array. Additionally, in assessing all possible arrays of 4-6 CR sensors, the recognition rates of the hybrid arrays (i.e. MPN + NW) were no better than that of the 4-sensor array containing only MPN CRs.

Artificial Affinity Proteins as Ligands of Immunoglobulins

PubMed Central

Mouratou, Barbara; Béhar, Ghislaine; Pecorari, Frédéric

2015-01-01

A number of natural proteins are known to have affinity and specificity for immunoglobulins. Some of them are widely used as reagents for detection or capture applications, such as Protein G and Protein A. However, these natural proteins have a defined spectrum of recognition that may not fit specific needs. With the development of combinatorial protein engineering and selection techniques, it has become possible to design artificial affinity proteins with the desired properties. These proteins, termed alternative scaffold proteins, are most often chosen for their stability, ease of engineering and cost-efficient recombinant production in bacteria. In this review, we focus on alternative scaffold proteins for which immunoglobulin binders have been identified and characterized. PMID:25647098

Ag-nanoparticles-decorated NiO-nanoflakes grafted Ni-nanorod arrays stuck out of porous AAO as effective SERS substrates.

PubMed

Zhou, Qitao; Meng, Guowen; Huang, Qing; Zhu, Chuhong; Tang, Haibin; Qian, Yiwu; Chen, Bin; Chen, Bensong

2014-02-28

NiO-nanoflakes (NiO-NFs) grafted Ni-nanorod (Ni-NR) arrays stuck out of the porous anodic aluminum oxide (AAO) template are achieved by a combinatorial process of AAO-confined electrodeposition of Ni-NRs, selectively etching part of the AAO template to expose the Ni-NRs, wet-etching the exposed Ni-NRs in ammonia to obtain Ni(OH)2-NFs grafted onto the cone-shaped Ni-NRs, and annealing to transform Ni(OH)2-NFs in situ into NiO-NFs. By top-view sputtering, Ag-nanoparticles (Ag-NPs) are decorated on each NiO-NFs grafted Ni-NR (denoted as NiO-NFs@Ni-NR). The resultant Ag-NPs-decorated NiO-NFs@Ni-NR (denoted as Ag-NPs@NiO-NFs@Ni-NR) arrays exhibit not only strong surface-enhanced Raman scattering (SERS) activity but also reproducible SERS-signals over the whole array. It is demonstrated that the strong SERS-activity is mainly ascribed to the high density of sub-10 nm gaps (hot spots) between the neighboring Ag-NPs, the semiconducting NiO-NFs induced chemical enhancement effect, and the lightning rod effect of the cone-shaped Ni-NRs. The three-level hierarchical nanostructure arrays stuck out of the AAO template can be utilized to probe polychlorinated biphenyls (PCBs, a kind of global environmental hazard) with a concentration as low as 5 × 10(-6) M, showing promising potential in SERS-based rapid detection of organic environmental pollutants.

Synthesis of Chemiluminescent Esters: A Combinatorial Synthesis Experiment for Organic Chemistry Students

ERIC Educational Resources Information Center

Duarte, Robert; Nielson, Janne T.; Dragojlovic, Veljko

2004-01-01

A group of techniques aimed at synthesizing a large number of structurally diverse compounds is called combinatorial synthesis. Synthesis of chemiluminescence esters using parallel combinatorial synthesis and mix-and-split combinatorial synthesis is experimented.

Do Dyslexic Individuals Present a Reduced Visual Attention Span? Evidence from Visual Recognition Tasks of Non-Verbal Multi-Character Arrays

ERIC Educational Resources Information Center

Yeari, Menahem; Isser, Michal; Schiff, Rachel

2017-01-01

A controversy has recently developed regarding the hypothesis that developmental dyslexia may be caused, in some cases, by a reduced visual attention span (VAS). To examine this hypothesis, independent of phonological abilities, researchers tested the ability of dyslexic participants to recognize arrays of unfamiliar visual characters. Employing…

Heterodimers of Retinoic Acid Receptors and Thyroid Hormone Receptors Display Unique Combinatorial Regulatory Properties

PubMed Central

Lee, Sangho; Privalsky, Martin L.

2009-01-01

Nuclear receptors are ligand-regulated transcription factors that regulate key aspects of metazoan development, differentiation, and homeostasis. Nuclear receptors recognize target genes by binding to specific DNA recognition sequences, denoted hormone response elements (HREs). Many nuclear receptors can recognize HREs as either homodimers or heterodimers. Retinoid X receptors (RXRs), in particular, serve as important heterodimer partners for many other nuclear receptors, including thyroid hormone receptors (TRs), and RXR/TR heterodimers have been proposed to be the primary mediators of target gene regulation by T3 hormone. Here, we report that the retinoic acid receptors (RARs), a distinct class of nuclear receptors, are also efficient heterodimer partners for TRs. These RAR/TR heterodimers form with similar affinities as RXR/TR heterodimers on an assortment of consensus and natural HREs, and preferentially assemble with the RAR partner 5′ of the TR moiety. The corepressor and coactivator recruitment properties of these RAR/TR heterodimers and their transcriptional activities in vivo are distinct from those observed with the corresponding RXR heterodimers. Our studies indicate that RXRs are not unique in their ability to partner with TRs, and that RARs can also serve as robust heterodimer partners and combinatorial regulators of T3-modulated gene expression. PMID:15650024

Sensor arrays for detecting microorganisms

NASA Technical Reports Server (NTRS)

Lewis, Nathan S. (Inventor); Freund, Michael S. (Inventor)

2000-01-01

A sensor array for detecting a microorganism comprising first and second sensors electrically connected to an electrical measuring apparatus, wherein the sensors comprise a region of nonconducting organic material and a region of conducting material compositionally that is different than the nonconducting organic material and an electrical path through the regions of nonconducting organic material and the conducting material. A system for identifying microorganisms using the sensor array, a computer and a pattern recognition algorithm, such as a neural net are also disclosed.

Asessing for Structural Understanding in Childrens' Combinatorial Problem Solving.

ERIC Educational Resources Information Center

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…

Life, Information, Entropy, and Time: Vehicles for Semantic Inheritance.

PubMed

Crofts, Antony R

2007-01-01

Attempts to understand how information content can be included in an accounting of the energy flux of the biosphere have led to the conclusion that, in information transmission, one component, the semantic content, or "the meaning of the message," adds no thermodynamic burden over and above costs arising from coding, transmission and translation. In biology, semantic content has two major roles. For all life forms, the message of the genotype encoded in DNA specifies the phenotype, and hence the organism that is tested against the real world through the mechanisms of Darwinian evolution. For human beings, communication through language and similar abstractions provides an additional supra-phenotypic vehicle for semantic inheritance, which supports the cultural heritages around which civilizations revolve. The following three postulates provide the basis for discussion of a number of themes that demonstrate some important consequences. (i) Information transmission through either pathway has thermodynamic components associated with data storage and transmission. (ii) The semantic content adds no additional thermodynamic cost. (iii) For all semantic exchange, meaning is accessible only through translation and interpretation, and has a value only in context. (1) For both pathways of semantic inheritance, translational and copying machineries are imperfect. As a consequence both pathways are subject to mutation and to evolutionary pressure by selection. Recognition of semantic content as a common component allows an understanding of the relationship between genes and memes, and a reformulation of Universal Darwinism. (2) The emergent properties of life are dependent on a processing of semantic content. The translational steps allow amplification in complexity through combinatorial possibilities in space and time. Amplification depends on the increased potential for complexity opened by 3D interaction specificity of proteins, and on the selection of useful variants by evolution. The initial interpretational steps include protein synthesis, molecular recognition, and catalytic potential that facilitate structural and functional roles. Combinatorial possibilities are extended through interactions of increasing complexity in the temporal dimension. (3) All living things show a behavior that indicates awareness of time, or chronognosis. The ∼4 billion years of biological evolution have given rise to forms with increasing sophistication in sensory adaptation. This has been linked to the development of an increasing chronognostic range, and an associated increase in combinatorial complexity. (4) Development of a modern human phenotype and the ability to communicate through language, led to the development of archival storage, and invention of the basic skills, institutions and mechanisms that allowed the evolution of modern civilizations. Combinatorial amplification at the supra-phenotypical level arose from the invention of syntax, grammar, numbers, and the subsequent developments of abstraction in writing, algorithms, etc. The translational machineries of the human mind, the "mutation" of ideas therein, and the "conversations" of our social intercourse, have allowed a limited set of symbolic descriptors to evolve into an exponentially expanding semantic heritage. (5) The three postulates above open interesting epistemological questions. An understanding of topics such dualism, the élan vital, the status of hypothesis in science, memetics, the nature of consciousness, the role of semantic processing in the survival of societies, and Popper's three worlds, require recognition of an insubstantial component. By recognizing a necessary linkage between semantic content and a physical machinery, we can bring these perennial problems into the framework of a realistic philosophy. It is suggested, following Popper, that the ∼4 billion years of evolution of the biosphere represents an exploration of the nature of reality at the physicochemical level, which, together with the conscious extension of this exploration through science and culture, provides a firm epistemological underpinning for such a philosophy.

Life, Information, Entropy, and Time

PubMed Central

Crofts, Antony R.

2008-01-01

Attempts to understand how information content can be included in an accounting of the energy flux of the biosphere have led to the conclusion that, in information transmission, one component, the semantic content, or “the meaning of the message,” adds no thermodynamic burden over and above costs arising from coding, transmission and translation. In biology, semantic content has two major roles. For all life forms, the message of the genotype encoded in DNA specifies the phenotype, and hence the organism that is tested against the real world through the mechanisms of Darwinian evolution. For human beings, communication through language and similar abstractions provides an additional supra-phenotypic vehicle for semantic inheritance, which supports the cultural heritages around which civilizations revolve. The following three postulates provide the basis for discussion of a number of themes that demonstrate some important consequences. (i) Information transmission through either pathway has thermodynamic components associated with data storage and transmission. (ii) The semantic content adds no additional thermodynamic cost. (iii) For all semantic exchange, meaning is accessible only through translation and interpretation, and has a value only in context. (1) For both pathways of semantic inheritance, translational and copying machineries are imperfect. As a consequence both pathways are subject to mutation and to evolutionary pressure by selection. Recognition of semantic content as a common component allows an understanding of the relationship between genes and memes, and a reformulation of Universal Darwinism. (2) The emergent properties of life are dependent on a processing of semantic content. The translational steps allow amplification in complexity through combinatorial possibilities in space and time. Amplification depends on the increased potential for complexity opened by 3D interaction specificity of proteins, and on the selection of useful variants by evolution. The initial interpretational steps include protein synthesis, molecular recognition, and catalytic potential that facilitate structural and functional roles. Combinatorial possibilities are extended through interactions of increasing complexity in the temporal dimension. (3) All living things show a behavior that indicates awareness of time, or chronognosis. The ∼4 billion years of biological evolution have given rise to forms with increasing sophistication in sensory adaptation. This has been linked to the development of an increasing chronognostic range, and an associated increase in combinatorial complexity. (4) Development of a modern human phenotype and the ability to communicate through language, led to the development of archival storage, and invention of the basic skills, institutions and mechanisms that allowed the evolution of modern civilizations. Combinatorial amplification at the supra-phenotypical level arose from the invention of syntax, grammar, numbers, and the subsequent developments of abstraction in writing, algorithms, etc. The translational machineries of the human mind, the “mutation” of ideas therein, and the “conversations” of our social intercourse, have allowed a limited set of symbolic descriptors to evolve into an exponentially expanding semantic heritage. (5) The three postulates above open interesting epistemological questions. An understanding of topics such dualism, the élan vital, the status of hypothesis in science, memetics, the nature of consciousness, the role of semantic processing in the survival of societies, and Popper's three worlds, require recognition of an insubstantial component. By recognizing a necessary linkage between semantic content and a physical machinery, we can bring these perennial problems into the framework of a realistic philosophy. It is suggested, following Popper, that the ∼4 billion years of evolution of the biosphere represents an exploration of the nature of reality at the physicochemical level, which, together with the conscious extension of this exploration through science and culture, provides a firm epistemological underpinning for such a philosophy. PMID:18978960

Advanced Catalysts for Fuel Cells

NASA Technical Reports Server (NTRS)

Narayanan, Sekharipuram R.; Whitacre, Jay; Valdez, T. I.

2006-01-01

This viewgraph presentation reviews the development of catalyst for Fuel Cells. The objectives of the project are to reduce the cost of stack components and reduce the amount of precious metal used in fuel cell construction. A rapid combinatorial screening technique based on multi-electrode thin film array has been developed and validated for identifying catalysts for oxygen reduction; focus shifted from methanol oxidation in FY05 to oxygen reduction in FY06. Multi-electrode arrays of thin film catalysts of Pt-Ni and Pt-Ni-Zr have been deposited. Pt-Ni and have been characterized electrochemically and structurally. Pt-Ni-Zr and Pt-Ni films show higher current density and onset potential compared to Pt. Electrocatalytic activity and onset potential are found to be strong function of the lattice constant. Thin film Pt(59)Ni(39)Zr(2) can provide 10 times the current density of thin film Pt. Thin film Pt(59)Ni(39)Zr(2) also shows 65mV higher onset potential than Pt.

Discovery of gigantic molecular nanostructures using a flow reaction array as a search engine.

PubMed

Zang, Hong-Ying; de la Oliva, Andreu Ruiz; Miras, Haralampos N; Long, De-Liang; McBurney, Roy T; Cronin, Leroy

2014-04-28

The discovery of gigantic molecular nanostructures like coordination and polyoxometalate clusters is extremely time-consuming since a vast combinatorial space needs to be searched, and even a systematic and exhaustive exploration of the available synthetic parameters relies on a great deal of serendipity. Here we present a synthetic methodology that combines a flow reaction array and algorithmic control to give a chemical 'real-space' search engine leading to the discovery and isolation of a range of new molecular nanoclusters based on [Mo(2)O(2)S(2)](2+)-based building blocks with either fourfold (C4) or fivefold (C5) symmetry templates and linkers. This engine leads us to isolate six new nanoscale cluster compounds: 1, {Mo(10)(C5)}; 2, {Mo(14)(C4)4(C5)2}; 3, {Mo(60)(C4)10}; 4, {Mo(48)(C4)6}; 5, {Mo(34)(C4)4}; 6, {Mo(18)(C4)9}; in only 200 automated experiments from a parameter space spanning ~5 million possible combinations.

Combinatorial synthesis and screening of non-biological polymers

DOEpatents

Schultz, Peter G.; Xiang, Xiao-Dong; Goldwasser, Isy; Briceno, Gabriel; Sun, Xiao-Dong; Wang, Kai-An

2006-04-25

Methods and apparatus for the preparation and use of a substrate having an array of diverse materials in predefined regions thereon. A substrate having an array of diverse materials thereon is generally prepared by delivering components of materials to predefined regions on a substrate, and simultaneously reacting the components to form at least two materials. Materials which can be prepared using the methods and apparatus of the present invention include, for example, covalent network solids, ionic solids and molecular solids. More particularly, materials which can be prepared using the methods and apparatus of the present invention include, for example, inorganic materials, intermetallic materials, metal alloys, ceramic materials, organic materials, organometallic materials, non-biological organic polymers, composite materials (e.g., inorganic composites, organic composites, or combinations thereof), etc. Once prepared, these materials can be screened for useful properties including, for example, electrical, thermal, mechanical, morphological, optical, magnetic, chemical, or other properties. Thus, the present invention provides methods for the parallel synthesis and analysis of novel materials having useful properties.

Combinatorial synthesis of novel materials

DOEpatents

Schultz, Peter G.; Xiang, Xiaodong; Goldwasser, Isy

1999-01-01

Methods and apparatus for the preparation and use of a substrate having an array of diverse materials in predefined regions thereon. A substrate having an array of diverse materials thereon is generally prepared by delivering components of materials to predefined regions on a substrate, and simultaneously reacting the components to form at least two materials. Materials which can be prepared using the methods and apparatus of the present invention include, for example, covalent network solids, ionic solids and molecular solids. More particularly, materials which can be prepared using the methods and apparatus of the present invention include, for example, inorganic materials, intermetallic materials, metal alloys, ceramic materials, organic materials, organometallic materials, non-biological organic polymers, composite materials (e.g., inorganic composites, organic composites, or combinations thereof), etc. Once prepared, these materials can be screened for useful properties including, for example, electrical, thermal, mechanical, morphological, optical, magnetic, chemical, or other properties. Thus, the present invention provides methods for the parallel synthesis and analysis of novel materials having useful properties.

Combinatorial sythesis of organometallic materials

DOEpatents

Schultz, Peter G.; Xiang, Xiaodong; Goldwasser, Isy

2002-07-16

Methods and apparatus for the preparation and use of a substrate having an array of diverse materials in predefined regions thereon. A substrate having an array of diverse materials thereon is generally prepared by delivering components of materials to predefined regions on a substrate, and simultaneously reacting the components to form at least two materials. Materials which can be prepared using the methods and apparatus of the present invention include, for example, covalent network solids, ionic solids and molecular solids. More particularly, materials which can be prepared using the methods and apparatus of the present invention include, for example, inorganic materials, intermetallic materials, metal alloys, ceramic materials, organic materials, organometallic materials, non-biological organic polymers, composite materials (e.g., inorganic composites, organic composites, or combinations thereof), etc. Once prepared, these materials can be screened for useful properties including, for example, electrical, thermal, mechanical, morphological, optical, magnetic, chemical, or other properties. Thus, the present invention provides methods for the parallel synthesis and analysis of novel materials having useful properties.

Combinatorial synthesis of novel materials

DOEpatents

Schultz, Peter G.; Xiang, Xiaodong; Goldwasser, Isy

2002-02-12

Methods and apparatus for the preparation and use of a substrate having an array of diverse materials in predefined regions thereon. A substrate having an array of diverse materials thereon is generally prepared by delivering components of materials to predefined regions on a substrate, and simultaneously reacting the components to form at least two materials. Materials which can be prepared using the methods and apparatus of the present invention include, for example, covalent network solids, ionic solids and molecular solids. More particularly, materials which can be prepared using the methods and apparatus of the present invention include, for example, inorganic materials, intermetallic materials, metal alloys, ceramic materials, organic materials, organometallic materials, non-biological organic polymers, composite materials (e.g., inorganic composites, organic composites, or combinations thereof), etc. Once prepared, these materials can be screened for useful properties including, for example, electrical, thermal, mechanical, morphological, optical, magnetic, chemical, or other properties. Thus, the present invention provides methods for the parallel synthesis and analysis of novel materials having useful properties.

Combinatorial synthesis of novel materials

DOEpatents

Schultz, Peter G.; Xiang, Xiaodong; Goldwasser, Isy

1999-12-21

Methods and apparatus for the preparation and use of a substrate having an array of diverse materials in predefined regions thereon. A substrate having an array of diverse materials thereon is generally prepared by delivering components of materials to predefined regions on a substrate, and simultaneously reacting the components to form at least two materials. Materials which can be prepared using the methods and apparatus of the present invention include, for example, covalent network solids, ionic solids and molecular solids. More particularly, materials which can be prepared using the methods and apparatus of the present invention include, for example, inorganic materials, intermetallic materials, metal alloys, ceramic materials, organic materials, organometallic materials, non-biological organic polymers, composite materials (e.g., inorganic composites, organic composites, or combinations thereof), etc. Once prepared, these materials can be screened for useful properties including, for example, electrical, thermal, mechanical, morphological, optical, magnetic, chemical, or other properties. Thus, the present invention provides methods for the parallel synthesis and analysis of novel materials having useful properties.

Combinatorial synthesis of novel materials

DOEpatents

Schultz, Peter G.; Xiang, Xiaodong; Goldwasser, Isy

2001-01-01

Methods and apparatus for the preparation and use of a substrate having an array of diverse materials in predefined regions thereon. A substrate having an array of diverse materials thereon is generally prepared by delivering components of materials to predefined regions on a substrate, and simultaneously reacting the components to form at least two materials. Materials which can be prepared using the methods and apparatus of the present invention include, for example, covalent network solids, ionic solids and molecular solids. More particularly, materials which can be prepared using the methods and apparatus of the present invention include, for example, inorganic materials, intermetallic materials, metal alloys, ceramic materials, organic materials, organometallic materials, non-biological organic polymers, composite materials (e.g., inorganic composites, organic composites, or combinations thereof), etc. Once prepared, these materials can be screened for useful properties including, for example, electrical, thermal, mechanical, morphological, optical, magnetic, chemical, or other properties. Thus, the present invention provides methods for the parallel synthesis and analysis of novel materials having useful properties.

Combinatorial screening of inorganic and organometallic materials

DOEpatents

Schultz, Peter G.; Xiang, Xiaodong; Goldwasser, Isy

2002-01-01

Methods and apparatus for the preparation and use of a substrate having an array of diverse materials in predefined regions thereon. A substrate having an array of diverse materials thereon is generally prepared by delivering components of materials to predefined regions on a substrate, and simultaneously reacting the components to form at least two materials. Materials which can be prepared using the methods and apparatus of the present invention include, for example, covalent network solids, ionic solids and molecular solids. More particularly, materials which can be prepared using the methods and apparatus of the present invention include, for example, inorganic materials, intermetallic materials, metal alloys, ceramic materials, organic materials, organometallic materials, non-biological organic polymers, composite materials (e.g., inorganic composites, organic composites, or combinations thereof), etc. Once prepared, these materials can be screened for useful properties including, for example, electrical, thermal, mechanical, morphological, optical, magnetic, chemical, or other properties. Thus, the present invention provides methods for the parallel synthesis and analysis of novel materials having useful properties.

One-Cell Doubling Evaluation by Living Arrays of Yeast, ODELAY!

DOE PAGES

Herricks, Thurston; Dilworth, David J.; Mast, Fred D.; ...

2016-11-16

Cell growth is a complex phenotype widely used in systems biology to gauge the impact of genetic and environmental perturbations. Due to the magnitude of genome-wide studies, resolution is often sacrificed in favor of throughput, creating a demand for scalable, time-resolved, quantitative methods of growth assessment. We present ODELAY (One-cell Doubling Evaluation by Living Arrays of Yeast), an automated and scalable growth analysis platform. High measurement density and single-cell resolution provide a powerful tool for large-scale multiparameter growth analysis based on the modeling of microcolony expansion on solid media. Pioneered in yeast but applicable to other colony forming organisms, ODELAYmore » extracts the three key growth parameters (lag time, doubling time, and carrying capacity) that define microcolony expansion from single cells, simultaneously permitting the assessment of population heterogeneity. The utility of ODELAY is illustrated using yeast mutants, revealing a spectrum of phenotypes arising from single and combinatorial growth parameter perturbations.« less

One-Cell Doubling Evaluation by Living Arrays of Yeast, ODELAY!

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herricks, Thurston; Dilworth, David J.; Mast, Fred D.

Cell growth is a complex phenotype widely used in systems biology to gauge the impact of genetic and environmental perturbations. Due to the magnitude of genome-wide studies, resolution is often sacrificed in favor of throughput, creating a demand for scalable, time-resolved, quantitative methods of growth assessment. We present ODELAY (One-cell Doubling Evaluation by Living Arrays of Yeast), an automated and scalable growth analysis platform. High measurement density and single-cell resolution provide a powerful tool for large-scale multiparameter growth analysis based on the modeling of microcolony expansion on solid media. Pioneered in yeast but applicable to other colony forming organisms, ODELAYmore » extracts the three key growth parameters (lag time, doubling time, and carrying capacity) that define microcolony expansion from single cells, simultaneously permitting the assessment of population heterogeneity. The utility of ODELAY is illustrated using yeast mutants, revealing a spectrum of phenotypes arising from single and combinatorial growth parameter perturbations.« less

Localized transfection on arrays of magnetic beads coated with PCR products.

PubMed

Isalan, Mark; Santori, Maria Isabel; Gonzalez, Cayetano; Serrano, Luis

2005-02-01

High-throughput gene analysis would benefit from new approaches for delivering DNA or RNA into cells. Here we describe a simple system that allows any molecular biology laboratory to carry out multiple, parallel cell transfections on microscope coverslip arrays. By using magnetically defined positions and PCR product-coated paramagnetic beads, we achieved transfection in a variety of cell lines. Beads may be added to the cells at any time, allowing both spatial and temporal control of transfection. Because the beads may be coated with more than one gene construct, the method can be used to achieve cotransfection within single cells. Furthermore, PCR-generated mutants may be conveniently screened, bypassing cloning and plasmid purification steps. We illustrated the applicability of the method by screening combinatorial peptide libraries, fused to GFP, to identify previously unknown cellular localization motifs. In this way, we identified several localizing peptides, including structured localization signals based around the scaffold of a single C2H2 zinc finger.

Hypergraph-Based Combinatorial Optimization of Matrix-Vector Multiplication

ERIC Educational Resources Information Center

Wolf, Michael Maclean

2009-01-01

Combinatorial scientific computing plays an important enabling role in computational science, particularly in high performance scientific computing. In this thesis, we will describe our work on optimizing matrix-vector multiplication using combinatorial techniques. Our research has focused on two different problems in combinatorial scientific…

Batch-processed semiconductor gas sensor array for the selective detection of NOx in automotive exhaust gas

NASA Astrophysics Data System (ADS)

Jang, Hani; Kim, Minki; Kim, Yongjun

2016-12-01

This paper reports on a semiconductor gas sensor array to detect nitrogen oxides (NOx) in automotive exhaust gas. The proposed semiconductor gas sensor array consisted of one common electrode and three individual electrodes to minimize the size of the sensor array, and three sensing layers [TiO2 + SnO2 (15 wt%), SnO2, and Ga2O3] were deposited using screen printing. In addition, sensing materials were sintered under the same conditions in order to take advantage of batch processing. The sensing properties of the proposed sensor array were verified by experimental measurements, and the selectivity improved by using pattern recognition.

Plasmonic Library Based on Substrate-Supported Gradiential Plasmonic Arrays

PubMed Central

2014-01-01

We present a versatile approach to produce macroscopic, substrate-supported arrays of plasmonic nanoparticles with well-defined interparticle spacing and a continuous particle size gradient. The arrays thus present a “plasmonic library” of locally noncoupling plasmonic particles of different sizes, which can serve as a platform for future combinatorial screening of size effects. The structures were prepared by substrate assembly of gold-core/poly(N-isopropylacrylamide)-shell particles and subsequent post-modification. Coupling of the localized surface plasmon resonance (LSPR) could be avoided since the polymer shell separates the encapsulated gold cores. To produce a particle array with a broad range of well-defined but laterally distinguishable particle sizes, the substrate was dip-coated in a growth solution, which resulted in an overgrowth of the gold cores controlled by the local exposure time. The kinetics was quantitatively analyzed and found to be diffusion rate controlled, allowing for precise tuning of particle size by adjusting the withdrawal speed. We determined the kinetics of the overgrowth process, investigated the LSPRs along the gradient by UV–vis extinction spectroscopy, and compared the spectroscopic results to the predictions from Mie theory, indicating the absence of local interparticle coupling. We finally discuss potential applications of these substrate-supported plasmonic particle libraries and perspectives toward extending the concept from size to composition variation and screening of plasmonic coupling effects. PMID:25137554

Combinatorial structures to modeling simple games and applications

NASA Astrophysics Data System (ADS)

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.

Colorimetric Recognition of Aldehydes and Ketones.

PubMed

Li, Zheng; Fang, Ming; LaGasse, Maria K; Askim, Jon R; Suslick, Kenneth S

2017-08-07

A colorimetric sensor array has been designed for the identification of and discrimination among aldehydes and ketones in vapor phase. Due to rapid chemical reactions between the solid-state sensor elements and gaseous analytes, distinct color difference patterns were produced and digitally imaged for chemometric analysis. The sensor array was developed from classical spot tests using aniline and phenylhydrazine dyes that enable molecular recognition of a wide variety of aliphatic or aromatic aldehydes and ketones, as demonstrated by hierarchical cluster, principal component, and support vector machine analyses. The aldehyde/ketone-specific sensors were further employed for differentiation among and identification of ten liquor samples (whiskies, brandy, vodka) and ethanol controls, showing its potential applications in the beverage industry. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Characteristics of Binary Spike-Time-Dependent Plasticity in HfO2-Based RRAM and Applications for Pattern Recognition

NASA Astrophysics Data System (ADS)

Zhou, Zheng; Liu, Chen; Shen, Wensheng; Dong, Zhen; Chen, Zhe; Huang, Peng; Liu, Lifeng; Liu, Xiaoyan; Kang, Jinfeng

2017-04-01

A binary spike-time-dependent plasticity (STDP) protocol based on one resistive-switching random access memory (RRAM) device was proposed and experimentally demonstrated in the fabricated RRAM array. Based on the STDP protocol, a novel unsupervised online pattern recognition system including RRAM synapses and CMOS neurons is developed. Our simulations show that the system can efficiently compete the handwritten digits recognition task, which indicates the feasibility of using the RRAM-based binary STDP protocol in neuromorphic computing systems to obtain good performance.

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

DOEpatents

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.

Drosophila Nanos acts as a molecular clamp that modulates the RNA-binding and repression activities of Pumilio

PubMed Central

Weidmann, Chase A; Qiu, Chen; Arvola, René M; Lou, Tzu-Fang; Killingsworth, Jordan; Campbell, Zachary T; Tanaka Hall, Traci M; Goldstrohm, Aaron C

2016-01-01

Collaboration among the multitude of RNA-binding proteins (RBPs) is ubiquitous, yet our understanding of these key regulatory complexes has been limited to single RBPs. We investigated combinatorial translational regulation by Drosophila Pumilio (Pum) and Nanos (Nos), which control development, fertility, and neuronal functions. Our results show how the specificity of one RBP (Pum) is modulated by cooperative RNA recognition with a second RBP (Nos) to synergistically repress mRNAs. Crystal structures of Nos-Pum-RNA complexes reveal that Nos embraces Pum and RNA, contributes sequence-specific contacts, and increases Pum RNA-binding affinity. Nos shifts the recognition sequence and promotes repression complex formation on mRNAs that are not stably bound by Pum alone, explaining the preponderance of sub-optimal Pum sites regulated in vivo. Our results illuminate the molecular mechanism of a regulatory switch controlling crucial gene expression programs, and provide a framework for understanding how the partnering of RBPs evokes changes in binding specificity that underlie regulatory network dynamics. DOI: http://dx.doi.org/10.7554/eLife.17096.001 PMID:27482653

Drosophila Nanos acts as a molecular clamp that modulates the RNA-binding and repression activities of Pumilio

DOE PAGES

Weidmann, Chase A.; Qiu, Chen; Arvola, René M.; ...

2016-08-02

Collaboration among the multitude of RNA-binding proteins (RBPs) is ubiquitous, yet our understanding of these key regulatory complexes has been limited to single RBPs. We investigated combinatorial translational regulation by Drosophila Pumilio (Pum) and Nanos (Nos), which control development, fertility, and neuronal functions. Our results show how the specificity of one RBP (Pum) is modulated by cooperative RNA recognition with a second RBP (Nos) to synergistically repress mRNAs. Crystal structures of Nos-Pum-RNA complexes reveal that Nos embraces Pum and RNA, contributes sequence-specific contacts, and increases Pum RNA-binding affinity. Nos shifts the recognition sequence and promotes repression complex formation on mRNAsmore » that are not stably bound by Pum alone, explaining the preponderance of sub-optimal Pum sites regulated in vivo. Our results illuminate the molecular mechanism of a regulatory switch controlling crucial gene expression programs, and provide a framework for understanding how the partnering of RBPs evokes changes in binding specificity that underlie regulatory network dynamics.« less

Drosophila Nanos acts as a molecular clamp that modulates the RNA-binding and repression activities of Pumilio

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weidmann, Chase A.; Qiu, Chen; Arvola, René M.

Collaboration among the multitude of RNA-binding proteins (RBPs) is ubiquitous, yet our understanding of these key regulatory complexes has been limited to single RBPs. We investigated combinatorial translational regulation by Drosophila Pumilio (Pum) and Nanos (Nos), which control development, fertility, and neuronal functions. Our results show how the specificity of one RBP (Pum) is modulated by cooperative RNA recognition with a second RBP (Nos) to synergistically repress mRNAs. Crystal structures of Nos-Pum-RNA complexes reveal that Nos embraces Pum and RNA, contributes sequence-specific contacts, and increases Pum RNA-binding affinity. Nos shifts the recognition sequence and promotes repression complex formation on mRNAsmore » that are not stably bound by Pum alone, explaining the preponderance of sub-optimal Pum sites regulated in vivo. Our results illuminate the molecular mechanism of a regulatory switch controlling crucial gene expression programs, and provide a framework for understanding how the partnering of RBPs evokes changes in binding specificity that underlie regulatory network dynamics.« less

Biochip microsystem for bioinformatics recognition and analysis

NASA Technical Reports Server (NTRS)

Lue, Jaw-Chyng (Inventor); Fang, Wai-Chi (Inventor)

2011-01-01

A system with applications in pattern recognition, or classification, of DNA assay samples. Because DNA reference and sample material in wells of an assay may be caused to fluoresce depending upon dye added to the material, the resulting light may be imaged onto an embodiment comprising an array of photodetectors and an adaptive neural network, with applications to DNA analysis. Other embodiments are described and claimed.

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

PubMed Central

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

A New Approach for Proving or Generating Combinatorial Identities

ERIC Educational Resources Information Center

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…

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

PubMed

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.

Array Biosensor for Toxin Detection: Continued Advances

PubMed Central

Taitt, Chris Rowe; Shriver-Lake, Lisa C.; Ngundi, Miriam M.; Ligler, Frances S.

2008-01-01

The following review focuses on progress made in the last five years with the NRL Array Biosensor, a portable instrument for rapid and simultaneous detection of multiple targets. Since 2003, the Array Biosensor has been automated and miniaturized for operation at the point-of-use. The Array Biosensor has also been used to demonstrate (1) quantitative immunoassays against an expanded number of toxins and toxin indicators in food and clinical fluids, and (2) the efficacy of semi-selective molecules as alternative recognition moieties. Blind trials, with unknown samples in a variety of matrices, have demonstrated the versatility, sensitivity, and reliability of the automated system. PMID:27873991

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

PubMed

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).

Genetically Engineered Natural Killer Cells as a Means for Adoptive Tumor Immunotherapy.

PubMed

Michen, Susanne; Temme, Achim

2016-01-01

Natural killer (NK) cells are lymphoid cells of the innate immune system; they stand at the first defense line against viruses and transformed cells. NK cells use an array of germline-encoded activating and inhibitory receptors that sense virus-infected cells or malignant cells displaying altered surface expression of activating and inhibitory NK cell ligands. They exert potent cytotoxic responses to cellular targets and thus are candidate effector cells for immunotherapy of cancer. In particular, the genetic engineering of NK cells with chimeric antigen receptors (CARs) against surface-expressed tumor-associated antigens (TAAs) seems promising. In the allogeneic context, gene-modified NK cells compared to T cells may be superior because they are short-lived effector cells and do not cause graft-versus-host disease. Furthermore, their anti-tumoral activity can be augmented by combinatorial use with therapeutic antibodies, chemotherapeutics, and radiation. Today, efforts are being undertaken for large-scale NK-cell expansion and their genetic engineering for adoptive cell transfer. With the recent advances in understanding the complex biological interactions that regulate NK cells, it is expected that the genetic engineering of NK cells and a combinatorial blockade of immune evasion mechanisms are required to exploit the full potential of NK-cell-based immunotherapies.

Identification of FVIII gene mutations in patients with hemophilia A using new combinatorial sequencing by hybridization

PubMed Central

Chetta, M.; Drmanac, A.; Santacroce, R.; Grandone, E.; Surrey, S.; Fortina, P.; Margaglione, M.

2008-01-01

BACKGROUND: Standard methods of mutation detection are time consuming in Hemophilia A (HA) rendering their application unavailable in some analysis such as prenatal diagnosis. OBJECTIVES: To evaluate the feasibility of combinatorial sequencing-by-hybridization (cSBH) as an alternative and reliable tool for mutation detection in FVIII gene. PATIENTS/METHODS: We have applied a new method of cSBH that uses two different colors for detection of multiple point mutations in the FVIII gene. The 26 exons encompassing the HA gene were analyzed in 7 newly diagnosed Italian patients and in 19 previously characterized individuals with FVIII deficiency. RESULTS: Data show that, when solution-phase TAMRA and QUASAR labeled 5-mer oligonucleotide sets mixed with unlabeled target PCR templates are co-hybridized in the presence of DNA ligase to universal 6-mer oligonucleotide probe-based arrays, a number of mutations can be successfully detected. The technique was reliable also in identifying a mutant FVIII allele in an obligate heterozygote. A novel missense mutation (Leu1843Thr) in exon 16 and three novel neutral polymorphisms are presented with an updated protocol for 2-color cSBH. CONCLUSIONS: cSBH is a reliable tool for mutation detection in FVIII gene and may represent a complementary method for the genetic screening of HA patients. PMID:20300295

Plasma Enhanced Growth of Carbon Nanotubes For Ultrasensitive Biosensors

NASA Technical Reports Server (NTRS)

Cassell, Alan M.; Meyyappan, M.

2004-01-01

The multitude of considerations facing nanostructure growth and integration lends itself to combinatorial optimization approaches. Rapid optimization becomes even more important with wafer-scale growth and integration processes. Here we discuss methodology for developing plasma enhanced CVD growth techniques for achieving individual, vertically aligned carbon nanostructures that show excellent properties as ultrasensitive electrodes for nucleic acid detection. We utilize high throughput strategies for optimizing the upstream and downstream processing and integration of carbon nanotube electrodes as functional elements in various device types. An overview of ultrasensitive carbon nanotube based sensor arrays for electrochemical bio-sensing applications and the high throughput methodology utilized to combine novel electrode technology with conventional MEMS processing will be presented.

Plasma Enhanced Growth of Carbon Nanotubes For Ultrasensitive Biosensors

NASA Technical Reports Server (NTRS)

Cassell, Alan M.; Li, J.; Ye, Q.; Koehne, J.; Chen, H.; Meyyappan, M.

2004-01-01

The multitude of considerations facing nanostructure growth and integration lends itself to combinatorial optimization approaches. Rapid optimization becomes even more important with wafer-scale growth and integration processes. Here we discuss methodology for developing plasma enhanced CVD growth techniques for achieving individual, vertically aligned carbon nanostructures that show excellent properties as ultrasensitive electrodes for nucleic acid detection. We utilize high throughput strategies for optimizing the upstream and downstream processing and integration of carbon nanotube electrodes as functional elements in various device types. An overview of ultrasensitive carbon nanotube based sensor arrays for electrochemical biosensing applications and the high throughput methodology utilized to combine novel electrode technology with conventional MEMS processing will be presented.

HTM Spatial Pooler With Memristor Crossbar Circuits for Sparse Biometric Recognition.

PubMed

James, Alex Pappachen; Fedorova, Irina; Ibrayev, Timur; Kudithipudi, Dhireesha

2017-06-01

Hierarchical Temporal Memory (HTM) is an online machine learning algorithm that emulates the neo-cortex. The development of a scalable on-chip HTM architecture is an open research area. The two core substructures of HTM are spatial pooler and temporal memory. In this work, we propose a new Spatial Pooler circuit design with parallel memristive crossbar arrays for the 2D columns. The proposed design was validated on two different benchmark datasets, face recognition, and speech recognition. The circuits are simulated and analyzed using a practical memristor device model and 0.18 μm IBM CMOS technology model. The databases AR, YALE, ORL, and UFI, are used to test the performance of the design in face recognition. TIMIT dataset is used for the speech recognition.

Dynamic combinatorial libraries: new opportunities in systems chemistry.

PubMed

Hunt, Rosemary A R; Otto, Sijbren

2011-01-21

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 these molecular networks at systems level is essential for their use as a selection tool and creates exciting new opportunities in systems chemistry. In this feature article we discuss selected examples and considerations related to the advanced exploitation of dynamic combinatorial libraries for their originally conceived purpose of identifying strong binding interactions. Also reviewed are examples illustrating a trend towards increasing complexity in terms of network behaviour and reversible chemistry. Finally, new applications of dynamic combinatorial chemistry in self-assembly, transport and self-replication are discussed.

Printing Peptide arrays with a complementary metal oxide semiconductor chip.

PubMed

Loeffler, Felix F; Cheng, Yun-Chien; Muenster, Bastian; Striffler, Jakob; Liu, Fanny C; Ralf Bischoff, F; Doersam, Edgar; Breitling, Frank; Nesterov-Mueller, Alexander

2013-01-01

: In this chapter, we discuss the state-of-the-art peptide array technologies, comparing the spot technique, lithographical methods, and microelectronic chip-based approaches. Based on this analysis, we describe a novel peptide array synthesis method with a microelectronic chip printer. By means of a complementary metal oxide semiconductor chip, charged bioparticles can be patterned on its surface. The bioparticles serve as vehicles to transfer molecule monomers to specific synthesis spots. Our chip offers 16,384 pixel electrodes on its surface with a spot-to-spot pitch of 100 μm. By switching the voltage of each pixel between 0 and 100 V separately, it is possible to generate arbitrary particle patterns for combinatorial molecule synthesis. Afterwards, the patterned chip surface serves as a printing head to transfer the particle pattern from its surface to a synthesis substrate. We conducted a series of proof-of-principle experiments to synthesize high-density peptide arrays. Our solid phase synthesis approach is based on the 9-fluorenylmethoxycarbonyl protection group strategy. After melting the particles, embedded monomers diffuse to the surface and participate in the coupling reaction to the surface. The method demonstrated herein can be easily extended to the synthesis of more complicated artificial molecules by using bioparticles with artificial molecular building blocks. The possibility of synthesizing artificial peptides was also shown in an experiment in which we patterned biotin particles in a high-density array format. These results open the road to the development of peptide-based functional modules for diverse applications in biotechnology.

cDREM: inferring dynamic combinatorial gene regulation.

PubMed

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.

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

PubMed

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.

Use of combinatorial chemistry to speed drug discovery.

PubMed

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.

Contributions of pocket depth and electrostatic interactions to affinity and selectivity of receptors for methylated lysine in water.

PubMed

Beaver, Joshua E; Peacor, Brendan C; Bain, Julianne V; James, Lindsey I; Waters, Marcey L

2015-03-21

Dynamic combinatorial chemistry was used to generate a set of receptors for peptides containing methylated lysine (KMen, n = 0-3) and study the contribution of electrostatic effects and pocket depth to binding affinity and selectivity. We found that changing the location of a carboxylate resulted in an increase in preference for KMe2, presumably based on ability to form a salt bridge with KMe2. The number of charged groups on either the receptor or peptide guest systematically varied the binding affinities to all guests by approximately 1-1.5 kcal mol(-1), with little influence on selectivity. Lastly, formation of a deeper pocket led to both increased affinity and selectivity for KMe3 over the lower methylation states. From these studies, we identified that the tightest binder was a receptor with greater net charge, with a Kd of 0.2 μM, and the receptor with the highest selectivity was the one with the deepest pocket, providing 14-fold selectivity between KMe3 and KMe2 and a Kd for KMe3 of 0.3 μM. This work provides key insights into approaches to improve binding affinity and selectivity in water, while also demonstrating the versatility of dynamic combinatorial chemistry for rapidly exploring the impact of subtle changes in receptor functionality on molecular recognition in water.

Fuzzy logic of Aristotelian forms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perlovsky, L.I.

1996-12-31

Model-based approaches to pattern recognition and machine vision have been proposed to overcome the exorbitant training requirements of earlier computational paradigms. However, uncertainties in data were found to lead to a combinatorial explosion of the computational complexity. This issue is related here to the roles of a priori knowledge vs. adaptive learning. What is the a-priori knowledge representation that supports learning? I introduce Modeling Field Theory (MFT), a model-based neural network whose adaptive learning is based on a priori models. These models combine deterministic, fuzzy, and statistical aspects to account for a priori knowledge, its fuzzy nature, and data uncertainties.more » In the process of learning, a priori fuzzy concepts converge to crisp or probabilistic concepts. The MFT is a convergent dynamical system of only linear computational complexity. Fuzzy logic turns out to be essential for reducing the combinatorial complexity to linear one. I will discuss the relationship of the new computational paradigm to two theories due to Aristotle: theory of Forms and logic. While theory of Forms argued that the mind cannot be based on ready-made a priori concepts, Aristotelian logic operated with just such concepts. I discuss an interpretation of MFT suggesting that its fuzzy logic, combining a-priority and adaptivity, implements Aristotelian theory of Forms (theory of mind). Thus, 2300 years after Aristotle, a logic is developed suitable for his theory of mind.« less

Combinatorial chemoenzymatic synthesis and high-throughput screening of sialosides.

PubMed

Chokhawala, Harshal A; Huang, Shengshu; Lau, Kam; Yu, Hai; Cheng, Jiansong; Thon, Vireak; Hurtado-Ziola, Nancy; Guerrero, Juan A; Varki, Ajit; Chen, Xi

2008-09-19

Although the vital roles of structures containing sialic acid in biomolecular recognition are well documented, limited information is available on how sialic acid structural modifications, sialyl linkages, and the underlying glycan structures affect the binding or the activity of sialic acid-recognizing proteins and related downstream biological processes. A novel combinatorial chemoenzymatic method has been developed for the highly efficient synthesis of biotinylated sialosides containing different sialic acid structures and different underlying glycans in 96-well plates from biotinylated sialyltransferase acceptors and sialic acid precursors. By transferring the reaction mixtures to NeutrAvidin-coated plates and assaying for the yields of enzymatic reactions using lectins recognizing sialyltransferase acceptors but not the sialylated products, the biotinylated sialoside products can be directly used, without purification, for high-throughput screening to quickly identify the ligand specificity of sialic acid-binding proteins. For a proof-of-principle experiment, 72 biotinylated alpha2,6-linked sialosides were synthesized in 96-well plates from 4 biotinylated sialyltransferase acceptors and 18 sialic acid precursors using a one-pot three-enzyme system. High-throughput screening assays performed in NeutrAvidin-coated microtiter plates show that whereas Sambucus nigra Lectin binds to alpha2,6-linked sialosides with high promiscuity, human Siglec-2 (CD22) is highly selective for a number of sialic acid structures and the underlying glycans in its sialoside ligands.

Molecular Basis of Substrate Recognition and Degradation by Human Presequence Protease

PubMed Central

King, John V.; Liang, Wenguang G.; Scherpelz, Kathryn P.; Schilling, Alexander B.; Meredith, Stephen C.; Tang, Wei-Jen

2014-01-01

Summary Human Presequence Protease (hPreP) is an M16 metalloprotease localized in mitochondria. There, hPreP facilitates proteostasis by utilizing a ∼13,300Å3 catalytic chamber to degrade a diverse array of potentially toxic peptides, including mitochondrial presequences and amyloid-β (Aβ), the latter of which contributes to Alzheimer's disease pathogenesis. Here we report crystal structures for hPreP alone and in complex with Aβ, which show that hPreP uses size-exclusion and charge complementation for substrate recognition. These structures also reveal hPreP-specific features that permit a diverse array of peptides, with distinct distributions of charged and hydrophobic residues, to be specifically captured, cleaved, and their amyloidogenic features destroyed. SAXS analysis demonstrates that hPreP in solution exists in dynamic equilibrium between closed and open states, with the former being preferred. Furthermore, Aβ binding induces the closed state and hPreP dimerization. Together, these data reveal the molecular basis for flexible yet specific substrate recognition and degradation by hPreP. PMID:24931469

Array based Discovery of Aptamer Pairs (Open Access Publisher’s Version)

DTIC Science & Technology

2014-12-11

Array-based Discovery of Aptamer Pairs Minseon Cho,†,‡ Seung Soo Oh,‡ Jeff Nie,§ Ron Stewart,§ Monte J. Radeke,⊥ Michael Eisenstein,†,‡ Peter J...bidentate” target recognition, with affinities greatly exceeding either monovalent component. DNA aptamers are especially well-suited for such...constructs, because they can be linked via standard synthesis techniques without requiring chemical conjugation. Unfortunately, aptamer pairs are difficult

Solution-Phase Photochemical Nanopatterning Enabled by High-Refractive-Index Beam Pen Arrays.

PubMed

Xie, Zhuang; Gordiichuk, Pavlo; Lin, Qing-Yuan; Meckes, Brian; Chen, Peng-Cheng; Sun, Lin; Du, Jingshan S; Zhu, Jinghan; Liu, Yuan; Dravid, Vinayak P; Mirkin, Chad A

2017-08-22

A high-throughput, solution-based, scanning-probe photochemical nanopatterning approach, which does not require the use of probes with subwavelength apertures, is reported. Specifically, pyramid arrays made from high-refractive-index polymeric materials were constructed and studied as patterning tools in a conventional liquid-phase beam pen lithography experiment. Two versions of the arrays were explored with either metal-coated or metal-free tips. Importantly, light can be channeled through both types of tips and the appropriate solution phase (e.g., H 2 O or CH 3 OH) and focused on subwavelength regions of a substrate to effect a photoreaction in solution that results in localized patterning of a self-assembled monolayer (SAM)-coated Au thin film substrate. Arrays with as many as 4500 pyramid-shaped probes were used to simultaneously initiate thousands of localized free-radical photoreactions (decomposition of a lithium acylphosphinate photoinitiator in an aqueous solution) that result in oxidative removal of the SAM. The technique is attractive since it allows one to rapidly generate features less than 200 nm in diameter, and the metal-free tips afford more than 10-fold higher intensity than the tips with nanoapertures over a micrometer propagation length. In principle, this mask-free method can be utilized as a versatile tool for performing a wide variety of photochemistries across multiple scales that may be important in high-throughput combinatorial screening applications related to chemistry, biology, and materials science.

The Advanced Gamma-ray Imaging System (AGIS): Real Time Stereoscopic Array Trigger

NASA Astrophysics Data System (ADS)

Byrum, K.; Anderson, J.; Buckley, J.; Cundiff, T.; Dawson, J.; Drake, G.; Duke, C.; Haberichter, B.; Krawzcynski, H.; Krennrich, F.; Madhavan, A.; Schroedter, M.; Smith, A.

2009-05-01

Future large arrays of Imaging Atmospheric Cherenkov telescopes (IACTs) such as AGIS and CTA are conceived to comprise of 50 - 100 individual telescopes each having a camera with 10**3 to 10**4 pixels. To maximize the capabilities of such IACT arrays with a low energy threshold, a wide field of view and a low background rate, a sophisticated array trigger is required. We describe the design of a stereoscopic array trigger that calculates image parameters and then correlates them across a subset of telescopes. Fast Field Programmable Gate Array technology allows to use lookup tables at the array trigger level to form a real-time pattern recognition trigger tht capitalizes on the multiple view points of the shower at different shower core distances. A proof of principle system is currently under construction. It is based on 400 MHz FPGAs and the goal is for camera trigger rates of up to 10 MHz and a tunable cosmic-ray background suppression at the array level.

MIFT: GIFT Combinatorial Geometry Input to VCS Code

DTIC Science & Technology

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

Neural Meta-Memes Framework for Combinatorial Optimization

NASA Astrophysics Data System (ADS)

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).

Fast neuromimetic object recognition using FPGA outperforms GPU implementations.

PubMed

Orchard, Garrick; Martin, Jacob G; Vogelstein, R Jacob; Etienne-Cummings, Ralph

2013-08-01

Recognition of objects in still images has traditionally been regarded as a difficult computational problem. Although modern automated methods for visual object recognition have achieved steadily increasing recognition accuracy, even the most advanced computational vision approaches are unable to obtain performance equal to that of humans. This has led to the creation of many biologically inspired models of visual object recognition, among them the hierarchical model and X (HMAX) model. HMAX is traditionally known to achieve high accuracy in visual object recognition tasks at the expense of significant computational complexity. Increasing complexity, in turn, increases computation time, reducing the number of images that can be processed per unit time. In this paper we describe how the computationally intensive and biologically inspired HMAX model for visual object recognition can be modified for implementation on a commercial field-programmable aate Array, specifically the Xilinx Virtex 6 ML605 evaluation board with XC6VLX240T FPGA. We show that with minor modifications to the traditional HMAX model we can perform recognition on images of size 128 × 128 pixels at a rate of 190 images per second with a less than 1% loss in recognition accuracy in both binary and multiclass visual object recognition tasks.

Mammalian Odor Information Recognition by Implanted Microsensor Array in vivo

NASA Astrophysics Data System (ADS)

Zhou, Jun; Dong, Qi; Zhuang, Liujing; Liu, Qingjun; Wang, Ping

2011-09-01

The mammalian olfactory system has an exquisite capacity to rapidly recognize and discriminate thousands of distinct odors in our environment. Our research group focus on reading information from olfactory bulb circuit of anethetized Sprague-Dawley rat and utilize artificial recognition system for odor discrimination. After being stimulated by three odors with concentration of 10 μM to rat nose, the response of mitral cells in olfactory bulb is recorded by eight channel microwire sensor array. In 20 sessions with 3 animals, we obtained 30 discriminated individual cells recordings. The average firing rates of the cells are Isoamyl acetate 26 Hz, Methoxybenzene 16 Hz, and Rose essential oil 11 Hz. By spike sorting, we detect peaks and analyze the interspike interval distribution. Further more, principal component analysis is applied to reduce the dimensionality of the data sets and classify the response.

Comparisons between mammalian and artificial olfaction based on arrays of carbon black-polymer composite vapor detectors.

PubMed

Lewis, Nathan S

2004-09-01

Arrays of broadly cross-reactive vapor sensors provide a man-made implementation of an olfactory system, in which an analyte elicits a response from many receptors and each receptor responds to a variety of analytes. Pattern recognition methods are then used to detect analytes based on the collective response of the sensor array. With the use of this architecture, arrays of chemically sensitive resistors made from composites of conductors and insulating organic polymers have been shown to robustly classify, identify, and quantify a diverse collection of organic vapors, even though no individual sensor responds selectively to a particular analyte. The properties and functioning of these arrays are inspired by advances in the understanding of biological olfaction, and in turn, evaluation of the performance of the man-made array provides suggestions regarding some of the fundamental odor detection principles of the mammalian olfactory system.

Micropatterned arrays of porous silicon: toward sensory biointerfaces.

PubMed

Flavel, Benjamin S; Sweetman, Martin J; Shearer, Cameron J; Shapter, Joseph G; Voelcker, Nicolas H

2011-07-01

We describe the fabrication of arrays of porous silicon spots by means of photolithography where a positive photoresist serves as a mask during the anodization process. In particular, photoluminescent arrays and porous silicon spots suitable for further chemical modification and the attachment of human cells were created. The produced arrays of porous silicon were chemically modified by means of a thermal hydrosilylation reaction that facilitated immobilization of the fluorescent dye lissamine, and alternatively, the cell adhesion peptide arginine-glycine-aspartic acid-serine. The latter modification enabled the selective attachment of human lens epithelial cells on the peptide functionalized regions of the patterns. This type of surface patterning, using etched porous silicon arrays functionalized with biological recognition elements, presents a new format of interfacing porous silicon with mammalian cells. Porous silicon arrays with photoluminescent properties produced by this patterning strategy also have potential applications as platforms for in situ monitoring of cell behavior.

Combinatorial synthesis of inorganic or composite materials

DOEpatents

Goldwasser, Isy; Ross, Debra A.; Schultz, Peter G.; Xiang, Xiao-Dong; Briceno, Gabriel; Sun, Xian-Dong; Wang, Kai-An

2010-08-03

Methods and apparatus for the preparation and use of a substrate having an array of diverse materials in predefined regions thereon. A substrate having an array of diverse materials thereon is generally prepared by delivering components of materials to predefined regions on a substrate, and simultaneously reacting the components to form at least two materials or, alternatively, allowing the components to interact to form at least two different materials. Materials which can be prepared using the methods and apparatus of the present invention include, for example, covalent network solids, ionic solids and molecular solids. More particularly, materials which can be prepared using the methods and apparatus of the present invention include, for example, inorganic materials, intermetallic materials, metal alloys, ceramic materials, organic materials, organometallic materials, nonbiological organic polymers, composite materials (e.g., inorganic composites, organic composites, or combinations thereof), etc. Once prepared, these materials can be screened for useful properties including, for example, electrical, thermal, mechanical, morphological, optical, magnetic, chemical, or other properties. Thus, the present invention provides methods for the parallel synthesis and analysis of novel materials having useful properties.

Discovery of gigantic molecular nanostructures using a flow reaction array as a search engine

PubMed Central

Zang, Hong-Ying; de la Oliva, Andreu Ruiz; Miras, Haralampos N.; Long, De-Liang; McBurney, Roy T.; Cronin, Leroy

2014-01-01

The discovery of gigantic molecular nanostructures like coordination and polyoxometalate clusters is extremely time-consuming since a vast combinatorial space needs to be searched, and even a systematic and exhaustive exploration of the available synthetic parameters relies on a great deal of serendipity. Here we present a synthetic methodology that combines a flow reaction array and algorithmic control to give a chemical ‘real-space’ search engine leading to the discovery and isolation of a range of new molecular nanoclusters based on [Mo2O2S2]2+-based building blocks with either fourfold (C4) or fivefold (C5) symmetry templates and linkers. This engine leads us to isolate six new nanoscale cluster compounds: 1, {Mo10(C5)}; 2, {Mo14(C4)4(C5)2}; 3, {Mo60(C4)10}; 4, {Mo48(C4)6}; 5, {Mo34(C4)4}; 6, {Mo18(C4)9}; in only 200 automated experiments from a parameter space spanning ~5 million possible combinations. PMID:24770632

Automating gene library synthesis by structure-based combinatorial protein engineering: examples from plant sesquiterpene synthases.

PubMed

Dokarry, Melissa; Laurendon, Caroline; O'Maille, Paul E

2012-01-01

Structure-based combinatorial protein engineering (SCOPE) is a homology-independent recombination method to create multiple crossover gene libraries by assembling defined combinations of structural elements ranging from single mutations to domains of protein structure. SCOPE was originally inspired by DNA shuffling, which mimics recombination during meiosis, where mutations from parental genes are "shuffled" to create novel combinations in the resulting progeny. DNA shuffling utilizes sequence identity between parental genes to mediate template-switching events (the annealing and extension of one parental gene fragment on another) in PCR reassembly reactions to generate crossovers and hence recombination between parental genes. In light of the conservation of protein structure and degeneracy of sequence, SCOPE was developed to enable the "shuffling" of distantly related genes with no requirement for sequence identity. The central principle involves the use of oligonucleotides to encode for crossover regions to choreograph template-switching events during PCR assembly of gene fragments to create chimeric genes. This approach was initially developed to create libraries of hybrid DNA polymerases from distantly related parents, and later developed to create a combinatorial mutant library of sesquiterpene synthases to explore the catalytic landscapes underlying the functional divergence of related enzymes. This chapter presents a simplified protocol of SCOPE that can be integrated with different mutagenesis techniques and is suitable for automation by liquid-handling robots. Two examples are presented to illustrate the application of SCOPE to create gene libraries using plant sesquiterpene synthases as the model system. In the first example, we outline how to create an active-site library as a series of complex mixtures of diverse mutants. In the second example, we outline how to create a focused library as an array of individual clones to distil minimal combinations of functionally important mutations. Through these examples, the principles of the technique are illustrated and the suitability of automating various aspects of the procedure for given applications are discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

FOREWORD: Focus on Combinatorial Materials Science Focus on Combinatorial Materials Science

NASA Astrophysics Data System (ADS)

Chikyo, Toyohiro

2011-10-01

About 15 years have passed since the introduction of modern combinatorial synthesis and high-throughput techniques for the development of novel inorganic materials; however, similar methods existed before. The most famous was reported in 1970 by Hanak who prepared composition-spread films of metal alloys by sputtering mixed-material targets. Although this method was innovative, it was rarely used because of the large amount of data to be processed. This problem is solved in the modern combinatorial material research, which is strongly related to computer data analysis and robotics. This field is still at the developing stage and may be enriched by new methods. Nevertheless, given the progress in measurement equipment and procedures, we believe the combinatorial approach will become a major and standard tool of materials screening and development. The first article of this journal, published in 2000, was titled 'Combinatorial solid state materials science and technology', and this focus issue aims to reintroduce this topic to the Science and Technology of Advanced Materials audience. It covers recent progress in combinatorial materials research describing new results in catalysis, phosphors, polymers and metal alloys for shape memory materials. Sophisticated high-throughput characterization schemes and innovative synthesis tools are also presented, such as spray deposition using nanoparticles or ion plating. On a technical note, data handling systems are introduced to familiarize researchers with the combinatorial methodology. We hope that through this focus issue a wide audience of materials scientists can learn about recent and future trends in combinatorial materials science and high-throughput experimentation.

Programmable synaptic devices for electronic neural nets

NASA Technical Reports Server (NTRS)

Moopenn, A.; Thakoor, A. P.

1990-01-01

The architecture, design, and operational characteristics of custom VLSI and thin film synaptic devices are described. The devices include CMOS-based synaptic chips containing 1024 reprogrammable synapses with a 6-bit dynamic range, and nonvolatile, write-once, binary synaptic arrays based on memory switching in hydrogenated amorphous silicon films. Their suitability for embodiment of fully parallel and analog neural hardware is discussed. Specifically, a neural network solution to an assignment problem of combinatorial global optimization, implemented in fully parallel hardware using the synaptic chips, is described. The network's ability to provide optimal and near optimal solutions over a time scale of few neuron time constants has been demonstrated and suggests a speedup improvement of several orders of magnitude over conventional search methods.

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

PubMed

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 Nano-Bio Interfaces.

PubMed

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.

Combinatorial computational chemistry approach for materials design: applications in deNOx catalysis, Fischer-Tropsch synthesis, lanthanoid complex, and lithium ion secondary battery.

PubMed

Koyama, Michihisa; Tsuboi, Hideyuki; Endou, Akira; Takaba, Hiromitsu; Kubo, Momoji; Del Carpio, Carlos A; Miyamoto, Akira

2007-02-01

Computational chemistry can provide fundamental knowledge regarding various aspects of materials. While its impact in scientific research is greatly increasing, its contributions to industrially important issues are far from satisfactory. In order to realize industrial innovation by computational chemistry, a new concept "combinatorial computational chemistry" has been proposed by introducing the concept of combinatorial chemistry to computational chemistry. This combinatorial computational chemistry approach enables theoretical high-throughput screening for materials design. In this manuscript, we review the successful applications of combinatorial computational chemistry to deNO(x) catalysts, Fischer-Tropsch catalysts, lanthanoid complex catalysts, and cathodes of the lithium ion secondary battery.

Recognition Imaging of Acetylated Chromatin Using a DNA Aptamer

PubMed Central

Lin, Liyun; Fu, Qiang; Williams, Berea A.R.; Azzaz, Abdelhamid M.; Shogren-Knaak, Michael A.; Chaput, John C.; Lindsay, Stuart

2009-01-01

Histone acetylation plays an important role in the regulation of gene expression. A DNA aptamer generated by in vitro selection to be highly specific for histone H4 protein acetylated at lysine 16 was used as a recognition element for atomic force microscopy-based recognition imaging of synthetic nucleosomal arrays with precisely controlled acetylation. The aptamer proved to be reasonably specific at recognizing acetylated histones, with recognition efficiencies of 60% on-target and 12% off-target. Though this selectivity is much poorer than the >2000:1 equilibrium specificity of the aptamer, it is a large improvement on the performance of a ChIP-quality antibody, which is not selective at all in this application, and it should permit high-fidelity recognition with repeated imaging. The ability to image the precise location of posttranslational modifications may permit nanometer-scale investigation of their effect on chromatin structure. PMID:19751687

A portable array biosensor for food safety

NASA Astrophysics Data System (ADS)

Golden, Joel P.; Ngundi, Miriam M.; Shriver-Lake, Lisa C.; Taitt, Chris R.; Ligler, Frances S.

2004-11-01

An array biosensor developed for simultaneous analysis of multiple samples has been utilized to develop assays for toxins and pathogens in a variety of foods. The biochemical component of the multi-analyte biosensor consists of a patterned array of biological recognition elements immobilized on the surface of a planar waveguide. A fluorescence assay is performed on the patterned surface, yielding an array of fluorescent spots, the locations of which are used to identify what analyte is present. Signal transduction is accomplished by means of a diode laser for fluorescence excitation, optical filters and a CCD camera for image capture. A laptop computer controls the miniaturized fluidics system and image capture. Results for four mycotoxin competition assays in buffer and food samples are presented.

High efficiency family shuffling based on multi-step PCR and in vivo DNA recombination in yeast: statistical and functional analysis of a combinatorial library between human cytochrome P450 1A1 and 1A2.

PubMed

Abécassis, V; Pompon, D; Truan, G

2000-10-15

The design of a family shuffling strategy (CLERY: Combinatorial Libraries Enhanced by Recombination in Yeast) associating PCR-based and in vivo recombination and expression in yeast is described. This strategy was tested using human cytochrome P450 CYP1A1 and CYP1A2 as templates, which share 74% nucleotide sequence identity. Construction of highly shuffled libraries of mosaic structures and reduction of parental gene contamination were two major goals. Library characterization involved multiprobe hybridization on DNA macro-arrays. The statistical analysis of randomly selected clones revealed a high proportion of chimeric genes (86%) and a homogeneous representation of the parental contribution among the sequences (55.8 +/- 2.5% for parental sequence 1A2). A microtiter plate screening system was designed to achieve colorimetric detection of polycyclic hydrocarbon hydroxylation by transformed yeast cells. Full sequences of five randomly picked and five functionally selected clones were analyzed. Results confirmed the shuffling efficiency and allowed calculation of the average length of sequence exchange and mutation rates. The efficient and statistically representative generation of mosaic structures by this type of family shuffling in a yeast expression system constitutes a novel and promising tool for structure-function studies and tuning enzymatic activities of multicomponent eucaryote complexes involving non-soluble enzymes.

Chemoinformatic Analysis of Combinatorial Libraries, Drugs, Natural Products and Molecular Libraries Small Molecule Repository

PubMed Central

Singh, Narender; Guha, Rajarshi; Giulianotti, Marc; Pinilla, Clemencia; Houghten, Richard; Medina-Franco, Jose L.

2009-01-01

A multiple criteria approach is presented, that is used to perform a comparative analysis of four recently developed combinatorial libraries to drugs, Molecular Libraries Small Molecule Repository (MLSMR) and natural products. The compound databases were assessed in terms of physicochemical properties, scaffolds and fingerprints. The approach enables the analysis of property space coverage, degree of overlap between collections, scaffold and structural diversity and overall structural novelty. The degree of overlap between combinatorial libraries and drugs was assessed using the R-NN curve methodology, which measures the density of chemical space around a query molecule embedded in the chemical space of a target collection. The combinatorial libraries studied in this work exhibit scaffolds that were not observed in the drug, MLSMR and natural products collections. The fingerprint-based comparisons indicate that these combinatorial libraries are structurally different to current drugs. The R-NN curve methodology revealed that a proportion of molecules in the combinatorial libraries are located within the property space of the drugs. However, the R-NN analysis also showed that there are a significant number of molecules in several combinatorial libraries that are located in sparse regions of the drug space. PMID:19301827

Molecular insights of protein contour recognition with ligand pharmacophoric sites through combinatorial library design and MD simulation in validating HTLV-1 PR inhibitors.

PubMed

Selvaraj, Chandrabose; Omer, Ankur; Singh, Poonam; Singh, Sanjeev Kumar

2015-01-01

Retroviruses HIV-1 and HTLV-1 are chiefly considered to be the most dangerous pathogens in Homo sapiens. These two viruses have structurally unique protease (PR) enzymes, which are having common function of its replication mechanism. Though HIV PR drugs failed to inhibit HTLV-1 infections, they emphatically emphasise the need for designing new lead compounds against HTLV-1 PR. Therefore, we tried to understand the binding level interactions through the charge environment present in both ligand and protein active sites. The domino effect illustrates that libraries of purvalanol-A are attuned to fill allosteric binding site of HTLV-1 PR through molecular recognition and shows proper binding of ligand pharmacophoric features in receptor contours. Our screening evaluates seven compounds from purvalanol-A libraries, and these compounds' pharmacophore searches for an appropriate place in the binding site and it places well according to respective receptor contour surfaces. Thus our result provides a platform for the progress of more effective compounds, which are better in free energy calculation, molecular docking, ADME and molecular dynamics studies. Finally, this research provided novel chemical scaffolds for HTLV-1 drug discovery.

Biomining of MoS2 with Peptide-based Smart Biomaterials.

PubMed

Cetinel, Sibel; Shen, Wei-Zheng; Aminpour, Maral; Bhomkar, Prasanna; Wang, Feng; Borujeny, Elham Rafie; Sharma, Kumakshi; Nayebi, Niloofar; Montemagno, Carlo

2018-02-20

Biomining of valuable metals using a target specific approach promises increased purification yields and decreased cost. Target specificity can be implemented with proteins/peptides, the biological molecules, responsible from various structural and functional pathways in living organisms by virtue of their specific recognition abilities towards both organic and inorganic materials. Phage display libraries are used to identify peptide biomolecules capable of specifically recognizing and binding organic/inorganic materials of interest with high affinities. Using combinatorial approaches, these molecular recognition elements can be converted into smart hybrid biomaterials and harnessed for biotechnological applications. Herein, we used a commercially available phage-display library to identify peptides with specific binding affinity to molybdenite (MoS 2 ) and used them to decorate magnetic NPs. These peptide-coupled NPs could capture MoS 2 under a variety of environmental conditions. The same batch of NPs could be re-used multiple times to harvest MoS 2 , clearly suggesting that this hybrid material was robust and recyclable. The advantages of this smart hybrid biomaterial with respect to its MoS 2 -binding specificity, robust performance under environmentally challenging conditions and its recyclability suggests its potential application in harvesting MoS 2 from tailing ponds and downstream mining processes.

A virtual library of constrained cyclic tetrapeptides that mimics all four side-chain orientations for over half the reverse turns in the protein data bank.

PubMed

Arbor, Sage; Marshall, Garland R

2009-02-01

Reverse turns are often recognition sites for protein/protein interactions and, therefore, valuable potential targets for determining recognition motifs in development of potential therapeutics. A virtual combinatorial library of cyclic tetrapeptides (CTPs) was generated and the bonds in the low-energy structures were overlapped with canonical reverse-turn Calpha-Cbeta bonds (Tran et al., J Comput Aided Mol Des 19(8):551-566, 2005) to determine the utility of CTPs as reverse-turn peptidomimetics. All reverse turns in the Protein Data Bank (PDB) with a crystal structures resolution < or = 3.0 A were classified into the same known canonical reverse-turn Calpha-Cbeta bond clusters (Tran et al., J Comput Aided Mol Des 19(8):551-566, 2005). CTP reverse-turn mimics were compiled that mimicked both the relative orientations of three of the four as well as all four Calpha-Cbeta bonds in the reverse turns of the PDB. 54% of reverse turns represented in the PDB had eight or more CTPs structures that mimicked the orientation of all four of the Calpha-Cbeta bonds in the reverse turn.

The Importance of Being Tyrosine: Lessons in Molecular Recognition from Minimalist Synthetic Binding Proteins

PubMed Central

Koide, Shohei; Sidhu, Sachdev S.

2010-01-01

Summary Combinatorial libraries built with severely restricted chemical diversity have yielded highly functional synthetic binding proteins. Structural analyses of these minimalist binding sites have revealed the dominant role of large tyrosine residues for mediating molecular contacts and of small serine/glycine residues for providing space and flexibility. The concept of using limited residue types to construct optimized binding proteins mirrors findings in the field of small molecule drug development, where it has been proposed that most drugs are built from a limited set of side chains presented by diverse frameworks. The physicochemical properties of tyrosine make it the amino acid that is most effective for mediating molecular recognition, and protein engineers have taken advantage of these characteristics to build tyrosine-rich protein binding sites that outperform natural proteins in terms of affinity and specificity. Knowledge from preceding studies can be used to improve current designs, and thus, synthetic protein libraries will continue to evolve and improve. In the near future, it seems likely that synthetic binding proteins will supersede natural antibodies for most purposes, and moreover, synthetic proteins will enable many new applications beyond the scope of natural proteins. PMID:19298050

Smooth Constrained Heuristic Optimization of a Combinatorial Chemical Space

DTIC Science & Technology

2015-05-01

ARL-TR-7294•MAY 2015 US Army Research Laboratory Smooth ConstrainedHeuristic Optimization of a Combinatorial Chemical Space by Berend Christopher...7294•MAY 2015 US Army Research Laboratory Smooth ConstrainedHeuristic Optimization of a Combinatorial Chemical Space by Berend Christopher...

Preparation of cherry-picked combinatorial libraries by string synthesis.

PubMed

Furka, Arpád; Dibó, Gábor; Gombosuren, Naran

2005-03-01

String synthesis [1-3] is an efficient and cheap manual method for preparation of combinatorial libraries by using macroscopic solid support units. Sorting the units between two synthetic steps is an important operation of the procedure. The software developed to guide sorting can be used only when complete combinatorial libraries are prepared. Since very often only selected components of the full libraries are needed, new software was constructed that guides sorting in preparation of non-complete combinatorial libraries. Application of the software is described in details.

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

ERIC Educational Resources Information Center

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)

Simple Learned Weighted Sums of Inferior Temporal Neuronal Firing Rates Accurately Predict Human Core Object Recognition Performance

PubMed Central

Hong, Ha; Solomon, Ethan A.; DiCarlo, James J.

2015-01-01

To go beyond qualitative models of the biological substrate of object recognition, we ask: can a single ventral stream neuronal linking hypothesis quantitatively account for core object recognition performance over a broad range of tasks? We measured human performance in 64 object recognition tests using thousands of challenging images that explore shape similarity and identity preserving object variation. We then used multielectrode arrays to measure neuronal population responses to those same images in visual areas V4 and inferior temporal (IT) cortex of monkeys and simulated V1 population responses. We tested leading candidate linking hypotheses and control hypotheses, each postulating how ventral stream neuronal responses underlie object recognition behavior. Specifically, for each hypothesis, we computed the predicted performance on the 64 tests and compared it with the measured pattern of human performance. All tested hypotheses based on low- and mid-level visually evoked activity (pixels, V1, and V4) were very poor predictors of the human behavioral pattern. However, simple learned weighted sums of distributed average IT firing rates exactly predicted the behavioral pattern. More elaborate linking hypotheses relying on IT trial-by-trial correlational structure, finer IT temporal codes, or ones that strictly respect the known spatial substructures of IT (“face patches”) did not improve predictive power. Although these results do not reject those more elaborate hypotheses, they suggest a simple, sufficient quantitative model: each object recognition task is learned from the spatially distributed mean firing rates (100 ms) of ∼60,000 IT neurons and is executed as a simple weighted sum of those firing rates. SIGNIFICANCE STATEMENT We sought to go beyond qualitative models of visual object recognition and determine whether a single neuronal linking hypothesis can quantitatively account for core object recognition behavior. To achieve this, we designed a database of images for evaluating object recognition performance. We used multielectrode arrays to characterize hundreds of neurons in the visual ventral stream of nonhuman primates and measured the object recognition performance of >100 human observers. Remarkably, we found that simple learned weighted sums of firing rates of neurons in monkey inferior temporal (IT) cortex accurately predicted human performance. Although previous work led us to expect that IT would outperform V4, we were surprised by the quantitative precision with which simple IT-based linking hypotheses accounted for human behavior. PMID:26424887

Bifurcation-based approach reveals synergism and optimal combinatorial perturbation.

PubMed

Liu, Yanwei; Li, Shanshan; Liu, Zengrong; Wang, Ruiqi

2016-06-01

Cells accomplish the process of fate decisions and form terminal lineages through a series of binary choices in which cells switch stable states from one branch to another as the interacting strengths of regulatory factors continuously vary. Various combinatorial effects may occur because almost all regulatory processes are managed in a combinatorial fashion. Combinatorial regulation is crucial for cell fate decisions because it may effectively integrate many different signaling pathways to meet the higher regulation demand during cell development. However, whether the contribution of combinatorial regulation to the state transition is better than that of a single one and if so, what the optimal combination strategy is, seem to be significant issue from the point of view of both biology and mathematics. Using the approaches of combinatorial perturbations and bifurcation analysis, we provide a general framework for the quantitative analysis of synergism in molecular networks. Different from the known methods, the bifurcation-based approach depends only on stable state responses to stimuli because the state transition induced by combinatorial perturbations occurs between stable states. More importantly, an optimal combinatorial perturbation strategy can be determined by investigating the relationship between the bifurcation curve of a synergistic perturbation pair and the level set of a specific objective function. The approach is applied to two models, i.e., a theoretical multistable decision model and a biologically realistic CREB model, to show its validity, although the approach holds for a general class of biological systems.

Automated real-time structure health monitoring via signature pattern recognition

NASA Astrophysics Data System (ADS)

Sun, Fanping P.; Chaudhry, Zaffir A.; Rogers, Craig A.; Majmundar, M.; Liang, Chen

1995-05-01

Described in this paper are the details of an automated real-time structure health monitoring system. The system is based on structural signature pattern recognition. It uses an array of piezoceramic patches bonded to the structure as integrated sensor-actuators, an electric impedance analyzer for structural frequency response function acquisition and a PC for control and graphic display. An assembled 3-bay truss structure is employed as a test bed. Two issues, the localization of sensing area and the sensor temperature drift, which are critical for the success of this technique are addressed and a novel approach of providing temperature compensation using probability correlation function is presented. Due to the negligible weight and size of the solid-state sensor array and its ability to sense incipient-type damage, the system can eventually be implemented on many types of structures such as aircraft, spacecraft, large-span dome roof and steel bridges requiring multilocation and real-time health monitoring.

A highly addressable static droplet array enabling digital control of a single droplet at pico-volume resolution.

PubMed

Jeong, Heon-Ho; Lee, Byungjin; Jin, Si Hyung; Jeong, Seong-Geun; Lee, Chang-Soo

2016-04-26

Droplet-based microfluidics enabling exquisite liquid-handling has been developed for diagnosis, drug discovery and quantitative biology. Compartmentalization of samples into a large number of tiny droplets is a great approach to perform multiplex assays and to improve reliability and accuracy using a limited volume of samples. Despite significant advances in microfluidic technology, individual droplet handling in pico-volume resolution is still a challenge in obtaining more efficient and varying multiplex assays. We present a highly addressable static droplet array (SDA) enabling individual digital manipulation of a single droplet using a microvalve system. In a conventional single-layer microvalve system, the number of microvalves required is dictated by the number of operation objects; thus, individual trap-and-release on a large-scale 2D array format is highly challenging. By integrating double-layer microvalves, we achieve a "balloon" valve that preserves the pressure-on state under released pressure; this valve can allow the selective releasing and trapping of 7200 multiplexed pico-droplets using only 1 μL of sample without volume loss. This selectivity and addressability completely arranged only single-cell encapsulated droplets from a mixture of droplet compositions via repetitive selective trapping and releasing. Thus, it will be useful for efficient handling of miniscule volumes of rare or clinical samples in multiplex or combinatory assays, and the selective collection of samples.

Photo- and electropatterning of hydrogel-encapsulated living cell arrays.

PubMed

Albrecht, Dirk R; Tsang, Valerie Liu; Sah, Robert L; Bhatia, Sangeeta N

2005-01-01

Living cells have the potential to serve as sensors, naturally integrating the response to stimuli to generate predictions about cell fate (e.g., differentiation, migration, proliferation, apoptosis). Miniaturized arrays of living cells further offer the capability to interrogate many cells in parallel and thereby enable high-throughput and/or combinatorial assays. However, the interface between living cells and synthetic chip platforms is a critical one wherein the cellular phenotype must be preserved to generate useful signals. While some cell types retain tissue-specific features on a flat (2-D) surface, it has become increasingly apparent that a 3-D physical environment will be required for others. In this paper, we present two independent methods for creating living cell arrays that are encapsulated within a poly(ethylene glycol)-based hydrogel to create a local 3-D microenvironment. First, 'photopatterning' selectively crosslinks hydrogel microstructures containing living cells with approximately 100 microm feature size. Second, 'electropatterning' utilizes dielectrophoretic forces to position cells within a prepolymer solution prior to crosslinking, forming cell patterns with micron resolution. We further combine these methods to obtain hierarchical control of cell positioning over length scales ranging from microns to centimeters. This level of microenvironmental control should enable the fabrication of next-generation cellular microarrays in which robust 3-D cultures of cells are presented with appropriate physical and chemical cues and, consequently, report on cellular responses that resemble in vivo behavior.

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

USDA-ARS?s Scientific Manuscript database

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...

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

ERIC Educational Resources Information Center

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…

Optimum Number of Anchored Clathrate Water and Its Instantaneous Fluctuations Dictate Ice Plane Recognition Specificities of Insect Antifreeze Protein.

PubMed

Chakraborty, Sandipan; Jana, Biman

2018-03-29

Ice recognition by antifreeze proteins (AFPs) is a subject of topical interest. Among several classes of AFPs, insect AFPs are hyperactive presumably due to their ability to adsorb on basal plane. However, the origin of the basal plane binding specificity is not clearly known. Present work aims to provide atomistic insight into the origin of basal plane recognition by an insect antifreeze protein. Free energy calculations reveal that the order of binding affinity of the AFP toward different ice planes is basal plane > prism plane > pyramidal plane. Critical insight reveals that the observed plane specificity is strongly correlated with the number and their instantaneous fluctuations of clathrate water forming hydrogen bonds with both ice binding surface (IBS) of AFP and ice surface, thus anchoring AFP to the ice surface. On basal plane, anchored clathrate water array is highly stable due to exact match in the periodicity of oxygen atom repeat distances of the ice surface and the threonine repeat distances at the IBS. The stability of anchored clathrate water array progressively decreases upon prism and pyramidal plane adsorption due to mismatch between the threonine ladder and oxygen atom repeat distance. Further analysis reveals that hydration around the methyl side-chains of threonine residues becomes highly significant at low temperature which stabilizes the anchored clathrate water array and dual hydrogen-bonding is a consequence of this stability. Structural insight gained from this study paves the way for rational designing of highly potent antifreeze-mimetic with potential industrial applications.

Cat-eye effect target recognition with single-pixel detectors

NASA Astrophysics Data System (ADS)

Jian, Weijian; Li, Li; Zhang, Xiaoyue

2015-12-01

A prototype of cat-eye effect target recognition with single-pixel detectors is proposed. Based on the framework of compressive sensing, it is possible to recognize cat-eye effect targets by projecting a series of known random patterns and measuring the backscattered light with three single-pixel detectors in different locations. The prototype only requires simpler, less expensive detectors and extends well beyond the visible spectrum. The simulations are accomplished to evaluate the feasibility of the proposed prototype. We compared our results to that obtained from conventional cat-eye effect target recognition methods using area array sensor. The experimental results show that this method is feasible and superior to the conventional method in dynamic and complicated backgrounds.

cGRNB: a web server for building combinatorial gene regulatory networks through integrated engineering of seed-matching sequence information and gene expression datasets.

PubMed

Xu, Huayong; Yu, Hui; Tu, Kang; Shi, Qianqian; Wei, Chaochun; Li, Yuan-Yuan; Li, Yi-Xue

2013-01-01

We are witnessing rapid progress in the development of methodologies for building the combinatorial gene regulatory networks involving both TFs (Transcription Factors) and miRNAs (microRNAs). There are a few tools available to do these jobs but most of them are not easy to use and not accessible online. A web server is especially needed in order to allow users to upload experimental expression datasets and build combinatorial regulatory networks corresponding to their particular contexts. In this work, we compiled putative TF-gene, miRNA-gene and TF-miRNA regulatory relationships from forward-engineering pipelines and curated them as built-in data libraries. We streamlined the R codes of our two separate forward-and-reverse engineering algorithms for combinatorial gene regulatory network construction and formalized them as two major functional modules. As a result, we released the cGRNB (combinatorial Gene Regulatory Networks Builder): a web server for constructing combinatorial gene regulatory networks through integrated engineering of seed-matching sequence information and gene expression datasets. The cGRNB enables two major network-building modules, one for MPGE (miRNA-perturbed gene expression) datasets and the other for parallel miRNA/mRNA expression datasets. A miRNA-centered two-layer combinatorial regulatory cascade is the output of the first module and a comprehensive genome-wide network involving all three types of combinatorial regulations (TF-gene, TF-miRNA, and miRNA-gene) are the output of the second module. In this article we propose cGRNB, a web server for building combinatorial gene regulatory networks through integrated engineering of seed-matching sequence information and gene expression datasets. Since parallel miRNA/mRNA expression datasets are rapidly accumulated by the advance of next-generation sequencing techniques, cGRNB will be very useful tool for researchers to build combinatorial gene regulatory networks based on expression datasets. The cGRNB web-server is free and available online at http://www.scbit.org/cgrnb.

Combinatorial effects on clumped isotopes and their significance in biogeochemistry

NASA Astrophysics Data System (ADS)

Yeung, Laurence Y.

2016-01-01

The arrangement of isotopes within a collection of molecules records their physical and chemical histories. Clumped-isotope analysis interrogates these arrangements, i.e., how often rare isotopes are bound together, which in many cases can be explained by equilibrium and/or kinetic isotope fractionation. However, purely combinatorial effects, rooted in the statistics of pairing atoms in a closed system, are also relevant, and not well understood. Here, I show that combinatorial isotope effects are most important when two identical atoms are neighbors on the same molecule (e.g., O2, N2, and D-D clumping in CH4). When the two halves of an atom pair are either assembled with different isotopic preferences or drawn from different reservoirs, combinatorial effects cause depletions in clumped-isotope abundance that are most likely between zero and -1‰, although they could potentially be -10‰ or larger for D-D pairs. These depletions are of similar magnitude, but of opposite sign, to low-temperature equilibrium clumped-isotope effects for many small molecules. Enzymatic isotope-pairing reactions, which can have site-specific isotopic fractionation factors and atom reservoirs, should express this class of combinatorial isotope effect, although it is not limited to biological reactions. Chemical-kinetic isotope effects, which are related to a bond-forming transition state, arise independently and express second-order combinatorial effects related to the abundance of the rare isotope. Heteronuclear moeties (e.g., Csbnd O and Csbnd H), are insensitive to direct combinatorial influences, but secondary combinatorial influences are evident. In general, both combinatorial and chemical-kinetic factors are important for calculating and interpreting clumped-isotope signatures of kinetically controlled reactions. I apply this analytical framework to isotope-pairing reactions relevant to geochemical oxygen, carbon, and nitrogen cycling that may be influenced by combinatorial clumped-isotope effects. These isotopic signatures, manifest as either directly bound isotope ;clumps; or as features of a molecule's isotopic anatomy, are linked to molecular mechanisms and may eventually provide additional information about biogeochemical cycling on environmentally relevant spatial scales.

Transcriptional Profiling of Human Peripheral Blood Mononuclear Cells Exposed to Bacillus anthracis in vitro

DTIC Science & Technology

2013-03-11

are derived from the combination of three polypeptides, namely the Protective antigen (PA, 83 kDa), the edema factor (EF, 89 kDa), and the lethal...p38MAPK-dependent pathways. The T-cell receptors and CD3-mediated antigenic recognition processes are possibly restrained, and the expression of CD79...NY), using a VersArray microarrayer ( Bio -Rad, CA). Arrays were post- processed using UV-cross linking at 1200 mJ/cm2, followed by baking for 4 hrs

Defense Small Business Innovation Research Program (SBIR). Volume 1. Army Abstracts of Phase 1 Awards 1991

DTIC Science & Technology

1991-01-01

Office: MICOM HUNTSVILLE, AL 35805 Contract #: DAAHO1-92-C-R150 Phone: (205) 876-7502 Pi: D. BRETI BEASLEY Title: INFRARED LASER DIODE BASED INFRARED ...TECHNIQUES WILL BE INVESTIGATED TO DESIGN A FORM FIT GIMBALL-MOUNTED 94 GHZ/ INFRARED FOCAL PLANE ARRAY DUAL-MODE MISSILE SEEKER SENSOR BASED ON LOW...RESOLUTION AT 94 GHZ AND A 128X128 ARRAY IR IMAGE PROCESSING FOR AUTONOMOUS TARGET RECOGNITION AND AIMPOINT SELECTION. THE 94 GHZ AND INFRARED ELECTRONICS

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

NASA Astrophysics Data System (ADS)

Gaifullin, A. A.

2008-10-01

To every oriented closed combinatorial manifold we assign the set (with repetitions) of isomorphism classes of links of its vertices. The resulting transformation \\mathcal{L} is the main object of study in this paper. We pose an inversion problem for \\mathcal{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 \\mathcal{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 \\mathcal{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 \\xi of a space X, this construction enables us to find explicitly a combinatorial manifold M and a map \\varphi\\colon M\\to X such that \\varphi_* \\lbrack M \\rbrack =r[\\xi] for some positive integer r. The construction is based on resolving singularities of \\xi. 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.

Training and Transfer in Combinatorial Problem Solving: The Development of Formal Reasoning During Early Adolescence

ERIC Educational Resources Information Center

Barratt, Barnaby B.

1975-01-01

This study investigated the emergence of combinatorial competence in early adolescence and the effectiveness of a programmed discovery training procedure. Significant increases in combinatorial skill with age were shown; it was found that the expression of this skill was significantly facilitated if problems involved concrete material of low…

Invention as a combinatorial process: evidence from US patents

PubMed Central

Youn, Hyejin; Strumsky, Deborah; Bettencourt, Luis M. A.; Lobo, José

2015-01-01

Invention has been commonly conceptualized as a search over a space of combinatorial possibilities. Despite the existence of a rich literature, spanning a variety of disciplines, elaborating on the recombinant nature of invention, we lack a formal and quantitative characterization of the combinatorial process underpinning inventive activity. Here, we use US patent records dating from 1790 to 2010 to formally characterize invention as a combinatorial process. To do this, we treat patented inventions as carriers of technologies and avail ourselves of the elaborate system of technology codes used by the United States Patent and Trademark Office to classify the technologies responsible for an invention's novelty. We find that the combinatorial inventive process exhibits an invariant rate of ‘exploitation’ (refinements of existing combinations of technologies) and ‘exploration’ (the development of new technological combinations). This combinatorial dynamic contrasts sharply with the creation of new technological capabilities—the building blocks to be combined—that has significantly slowed down. We also find that, notwithstanding the very reduced rate at which new technologies are introduced, the generation of novel technological combinations engenders a practically infinite space of technological configurations. PMID:25904530

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

PubMed

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 Methods for Exploring Complex Materials

NASA Astrophysics Data System (ADS)

Amis, Eric J.

2004-03-01

Combinatorial and high-throughput methods have changed the paradigm of pharmaceutical synthesis and have begun to have a similar impact on materials science research. Already there are examples of combinatorial methods used for inorganic materials, catalysts, and polymer synthesis. For many investigations the primary goal has been discovery of new material compositions that optimize properties such as phosphorescence or catalytic activity. In the midst of the excitement generated to "make things", another opportunity arises for materials science to "understand things" by using the efficiency of combinatorial methods. We have shown that combinatorial methods hold potential for rapid and systematic generation of experimental data over the multi-parameter space typical of investigations in polymer physics. We have applied the combinatorial approach to studies of polymer thin films, biomaterials, polymer blends, filled polymers, and semicrystalline polymers. By combining library fabrication, high-throughput measurements, informatics, and modeling we can demonstrate validation of the methodology, new observations, and developments toward predictive models. This talk will present some of our latest work with applications to coating stability, multi-component formulations, and nanostructure assembly.

Tumor-targeting peptides from combinatorial libraries*

PubMed Central

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

Identification of combinatorial drug regimens for treatment of Huntington's disease using Drosophila

NASA Astrophysics Data System (ADS)

Agrawal, Namita; Pallos, Judit; Slepko, Natalia; Apostol, Barbara L.; Bodai, Laszlo; Chang, Ling-Wen; Chiang, Ann-Shyn; Michels Thompson, Leslie; Marsh, J. Lawrence

2005-03-01

We explore the hypothesis that pathology of Huntington's disease involves multiple cellular mechanisms whose contributions to disease are incrementally additive or synergistic. We provide evidence that the photoreceptor neuron degeneration seen in flies expressing mutant human huntingtin correlates with widespread degenerative events in the Drosophila CNS. We use a Drosophila Huntington's disease model to establish dose regimens and protocols to assess the effectiveness of drug combinations used at low threshold concentrations. These proof of principle studies identify at least two potential combinatorial treatment options and illustrate a rapid and cost-effective paradigm for testing and optimizing combinatorial drug therapies while reducing side effects for patients with neurodegenerative disease. The potential for using prescreening in Drosophila to inform combinatorial therapies that are most likely to be effective for testing in mammals is discussed. combinatorial treatments | neurodegeneration

Nonparametric Combinatorial Sequence Models

NASA Astrophysics Data System (ADS)

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

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 paper 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 sequence datasets 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 induced by the prior. By integrating out the posterior our method compares favorably to leading binding predictors.

Differential Effector Engagement by Oncogenic KRAS.

PubMed

Yuan, Tina L; Amzallag, Arnaud; Bagni, Rachel; Yi, Ming; Afghani, Shervin; Burgan, William; Fer, Nicole; Strathern, Leslie A; Powell, Katie; Smith, Brian; Waters, Andrew M; Drubin, David; Thomson, Ty; Liao, Rosy; Greninger, Patricia; Stein, Giovanna T; Murchie, Ellen; Cortez, Eliane; Egan, Regina K; Procter, Lauren; Bess, Matthew; Cheng, Kwong Tai; Lee, Chih-Shia; Lee, Liam Changwoo; Fellmann, Christof; Stephens, Robert; Luo, Ji; Lowe, Scott W; Benes, Cyril H; McCormick, Frank

2018-02-13

KRAS can bind numerous effector proteins, which activate different downstream signaling events. The best known are RAF, phosphatidylinositide (PI)-3' kinase, and RalGDS families, but many additional direct and indirect effectors have been reported. We have assessed how these effectors contribute to several major phenotypes in a quantitative way, using an arrayed combinatorial siRNA screen in which we knocked down 41 KRAS effectors nodes in 92 cell lines. We show that every cell line has a unique combination of effector dependencies, but in spite of this heterogeneity, we were able to identify two major subtypes of KRAS mutant cancers of the lung, pancreas, and large intestine, which reflect different KRAS effector engagement and opportunities for therapeutic intervention. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Recent Advances in the Discovery and Development of Marine Microbial Natural Products

PubMed Central

Xiong, Zhi-Qiang; Wang, Jian-Feng; Hao, Yu-You; Wang, Yong

2013-01-01

Marine microbial natural products (MMNPs) have attracted increasing attention from microbiologists, taxonomists, ecologists, agronomists, chemists and evolutionary biologists during the last few decades. Numerous studies have indicated that diverse marine microbes appear to have the capacity to produce an impressive array of MMNPs exhibiting a wide variety of biological activities such as antimicrobial, anti-tumor, anti-inflammatory and anti-cardiovascular agents. Marine microorganisms represent an underexplored reservoir for the discovery of MMNPs with unique scaffolds and for exploitation in the pharmaceutical and agricultural industries. This review focuses on MMNPs discovery and development over the past decades, including innovative isolation and culture methods, strategies for discovering novel MMNPs via routine screenings, metagenomics, genomics, combinatorial biosynthesis, and synthetic biology. The potential problems and future directions for exploring MMNPs are also discussed. PMID:23528949

Recombinant protein expression and purification: a comprehensive review of affinity tags and microbial applications.

PubMed

Young, Carissa L; Britton, Zachary T; Robinson, Anne S

2012-05-01

Protein fusion tags are indispensible tools used to improve recombinant protein expression yields, enable protein purification, and accelerate the characterization of protein structure and function. Solubility-enhancing tags, genetically engineered epitopes, and recombinant endoproteases have resulted in a versatile array of combinatorial elements that facilitate protein detection and purification in microbial hosts. In this comprehensive review, we evaluate the most frequently used solubility-enhancing and affinity tags. Furthermore, we provide summaries of well-characterized purification strategies that have been used to increase product yields and have widespread application in many areas of biotechnology including drug discovery, therapeutics, and pharmacology. This review serves as an excellent literature reference for those working on protein fusion tags. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Recent advances in the discovery and development of marine microbial natural products.

PubMed

Xiong, Zhi-Qiang; Wang, Jian-Feng; Hao, Yu-You; Wang, Yong

2013-03-08

Marine microbial natural products (MMNPs) have attracted increasing attention from microbiologists, taxonomists, ecologists, agronomists, chemists and evolutionary biologists during the last few decades. Numerous studies have indicated that diverse marine microbes appear to have the capacity to produce an impressive array of MMNPs exhibiting a wide variety of biological activities such as antimicrobial, anti-tumor, anti-inflammatory and anti-cardiovascular agents. Marine microorganisms represent an underexplored reservoir for the discovery of MMNPs with unique scaffolds and for exploitation in the pharmaceutical and agricultural industries. This review focuses on MMNPs discovery and development over the past decades, including innovative isolation and culture methods, strategies for discovering novel MMNPs via routine screenings, metagenomics, genomics, combinatorial biosynthesis, and synthetic biology. The potential problems and future directions for exploring MMNPs are also discussed.

Molecular biomimetics: nanotechnology through biology.

PubMed

Sarikaya, Mehmet; Tamerler, Candan; Jen, Alex K-Y; Schulten, Klaus; Baneyx, François

2003-09-01

Proteins, through their unique and specific interactions with other macromolecules and inorganics, control structures and functions of all biological hard and soft tissues in organisms. Molecular biomimetics is an emerging field in which hybrid technologies are developed by using the tools of molecular biology and nanotechnology. Taking lessons from biology, polypeptides can now be genetically engineered to specifically bind to selected inorganic compounds for applications in nano- and biotechnology. This review discusses combinatorial biological protocols, that is, bacterial cell surface and phage-display technologies, in the selection of short sequences that have affinity to (noble) metals, semiconducting oxides and other technological compounds. These genetically engineered proteins for inorganics (GEPIs) can be used in the assembly of functional nanostructures. Based on the three fundamental principles of molecular recognition, self-assembly and DNA manipulation, we highlight successful uses of GEPI in nanotechnology.

Synergistic Effect of Combinatorial Treatment with Curcumin and Mitomycin C on the Induction of Apoptosis of Breast Cancer Cells: A cDNA Microarray Analysis

PubMed Central

Zhou, Qian-Mei; Chen, Qi-Long; Du, Jia; Wang, Xiu-Feng; Lu, Yi-Yu; Zhang, Hui; Su, Shi-Bing

2014-01-01

In order to explore the synergistic mechanisms of combinatorial treatment using curcumin and mitomycin C (MMC) for breast cancer, MCF-7 breast cancer xenografts were conducted to observe the synergistic effect of combinatorial treatment using curcumin and MMC at various dosages. The synergistic mechanisms of combinatorial treatment using curcumin and MMC on the inhibition of tumor growth were explored by differential gene expression profile, gene ontology (GO), ingenuity pathway analysis (IPA) and Signal–Net network analysis. The expression levels of selected genes identified by cDNA microarray expression profiling were validated by quantitative RT-PCR (qRT-PCR) and Western blot analysis. Effect of combinatorial treatment on the inhibition of cell growth was observed by MTT assay. Apoptosis was detected by flow cytometric analysis and Hoechst 33258 staining. The combinatorial treatment of 100 mg/kg curcumin and 1.5 mg/kg MMC revealed synergistic inhibition on tumor growth. Among 1501 differentially expressed genes, the expression of 25 genes exhibited an obvious change and a significant difference in 27 signal pathways was observed (p < 0.05). In addition, Mapk1 (ERK) and Mapk14 (MAPK p38) had more cross-interactions with other genes and revealed an increase in expression by 8.14- and 11.84-fold, respectively during the combinatorial treatment by curcumin and MMC when compared with the control. Moreover, curcumin can synergistically improve tumoricidal effect of MMC in another human breast cancer MDA-MB-231 cells. Apoptosis was significantly induced by the combinatorial treatment (p < 0.05) and significantly inhibited by ERK inhibitor (PD98059) in MCF-7 cells (p < 0.05). The synergistic effect of combinatorial treatment by curcumin and MMC on the induction of apoptosis in breast cancer cells may be via the ERK pathway. PMID:25226537

Combinatorial theory of Macdonald polynomials I: proof of Haglund's formula.

PubMed

Haglund, J; Haiman, M; Loehr, N

2005-02-22

Haglund recently proposed a combinatorial interpretation of the modified Macdonald polynomials H(mu). We give a combinatorial proof of this conjecture, which establishes the existence and integrality of H(mu). As corollaries, we obtain the cocharge formula of Lascoux and Schutzenberger for Hall-Littlewood polynomials, a formula of Sahi and Knop for Jack's symmetric functions, a generalization of this result to the integral Macdonald polynomials J(mu), a formula for H(mu) in terms of Lascoux-Leclerc-Thibon polynomials, and combinatorial expressions for the Kostka-Macdonald coefficients K(lambda,mu) when mu is a two-column shape.

Signal dimensionality and the emergence of combinatorial structure.

PubMed

Little, Hannah; Eryılmaz, Kerem; de Boer, Bart

2017-11-01

In language, a small number of meaningless building blocks can be combined into an unlimited set of meaningful utterances. This is known as combinatorial structure. One hypothesis for the initial emergence of combinatorial structure in language is that recombining elements of signals solves the problem of overcrowding in a signal space. Another hypothesis is that iconicity may impede the emergence of combinatorial structure. However, how these two hypotheses relate to each other is not often discussed. In this paper, we explore how signal space dimensionality relates to both overcrowding in the signal space and iconicity. We use an artificial signalling experiment to test whether a signal space and a meaning space having similar topologies will generate an iconic system and whether, when the topologies differ, the emergence of combinatorially structured signals is facilitated. In our experiments, signals are created from participants' hand movements, which are measured using an infrared sensor. We found that participants take advantage of iconic signal-meaning mappings where possible. Further, we use trajectory predictability, measures of variance, and Hidden Markov Models to measure the use of structure within the signals produced and found that when topologies do not match, then there is more evidence of combinatorial structure. The results from these experiments are interpreted in the context of the differences between the emergence of combinatorial structure in different linguistic modalities (speech and sign). Copyright © 2017 Elsevier B.V. All rights reserved.

The Advanced Gamma-ray Imaging System (AGIS): Topological Array Trigger

NASA Astrophysics Data System (ADS)

Smith, Andrew W.

2010-03-01

AGIS is a concept for the next-generation ground-based gamma-ray observatory. It will be an array of 36 imaging atmospheric Cherenkov telescopes (IACTs) sensitive in the energy range from 50 GeV to 200 TeV. The required improvements in sensitivity, angular resolution, and reliability of operation relative to the present generation instruments imposes demanding technological and cost requirements on the design of the telescopes and on the triggering and readout systems for AGIS. To maximize the capabilities of large arrays of IACTs with a low energy threshold, a wide field of view and a low background rate, a sophisticated array trigger is required. We outline the status of the development of a stereoscopic array trigger that calculates image parameters and correlates them across a subset of telescopes. Field Programmable Gate Arrays (FPGAs) implement the real-time pattern recognition to suppress cosmic rays and night-sky background events. A proof of principle system is being developed to run at camera trigger rates up to 10MHz and array-level rates up to 10kHz.

Recognition and localization of speech by adult cochlear implant recipients wearing a digital hearing aid in the nonimplanted ear (bimodal hearing).

PubMed

Potts, Lisa G; Skinner, Margaret W; Litovsky, Ruth A; Strube, Michael J; Kuk, Francis

2009-06-01

The use of bilateral amplification is now common clinical practice for hearing aid users but not for cochlear implant recipients. In the past, most cochlear implant recipients were implanted in one ear and wore only a monaural cochlear implant processor. There has been recent interest in benefits arising from bilateral stimulation that may be present for cochlear implant recipients. One option for bilateral stimulation is the use of a cochlear implant in one ear and a hearing aid in the opposite nonimplanted ear (bimodal hearing). This study evaluated the effect of wearing a cochlear implant in one ear and a digital hearing aid in the opposite ear on speech recognition and localization. A repeated-measures correlational study was completed. Nineteen adult Cochlear Nucleus 24 implant recipients participated in the study. The participants were fit with a Widex Senso Vita 38 hearing aid to achieve maximum audibility and comfort within their dynamic range. Soundfield thresholds, loudness growth, speech recognition, localization, and subjective questionnaires were obtained six-eight weeks after the hearing aid fitting. Testing was completed in three conditions: hearing aid only, cochlear implant only, and cochlear implant and hearing aid (bimodal). All tests were repeated four weeks after the first test session. Repeated-measures analysis of variance was used to analyze the data. Significant effects were further examined using pairwise comparison of means or in the case of continuous moderators, regression analyses. The speech-recognition and localization tasks were unique, in that a speech stimulus presented from a variety of roaming azimuths (140 degree loudspeaker array) was used. Performance in the bimodal condition was significantly better for speech recognition and localization compared to the cochlear implant-only and hearing aid-only conditions. Performance was also different between these conditions when the location (i.e., side of the loudspeaker array that presented the word) was analyzed. In the bimodal condition, the speech-recognition and localization tasks were equal regardless of which side of the loudspeaker array presented the word, while performance was significantly poorer for the monaural conditions (hearing aid only and cochlear implant only) when the words were presented on the side with no stimulation. Binaural loudness summation of 1-3 dB was seen in soundfield thresholds and loudness growth in the bimodal condition. Measures of the audibility of sound with the hearing aid, including unaided thresholds, soundfield thresholds, and the Speech Intelligibility Index, were significant moderators of speech recognition and localization. Based on the questionnaire responses, participants showed a strong preference for bimodal stimulation. These findings suggest that a well-fit digital hearing aid worn in conjunction with a cochlear implant is beneficial to speech recognition and localization. The dynamic test procedures used in this study illustrate the importance of bilateral hearing for locating, identifying, and switching attention between multiple speakers. It is recommended that unilateral cochlear implant recipients, with measurable unaided hearing thresholds, be fit with a hearing aid.

Neuromorphic Hardware Architecture Using the Neural Engineering Framework for Pattern Recognition.

PubMed

Wang, Runchun; Thakur, Chetan Singh; Cohen, Gregory; Hamilton, Tara Julia; Tapson, Jonathan; van Schaik, Andre

2017-06-01

We present a hardware architecture that uses the neural engineering framework (NEF) to implement large-scale neural networks on field programmable gate arrays (FPGAs) for performing massively parallel real-time pattern recognition. NEF is a framework that is capable of synthesising large-scale cognitive systems from subnetworks and we have previously presented an FPGA implementation of the NEF that successfully performs nonlinear mathematical computations. That work was developed based on a compact digital neural core, which consists of 64 neurons that are instantiated by a single physical neuron using a time-multiplexing approach. We have now scaled this approach up to build a pattern recognition system by combining identical neural cores together. As a proof of concept, we have developed a handwritten digit recognition system using the MNIST database and achieved a recognition rate of 96.55%. The system is implemented on a state-of-the-art FPGA and can process 5.12 million digits per second. The architecture and hardware optimisations presented offer high-speed and resource-efficient means for performing high-speed, neuromorphic, and massively parallel pattern recognition and classification tasks.

To Think without Thinking: The Implications of Combinatory Play and the Creative Process for Neuroaesthetics

ERIC Educational Resources Information Center

Stevens, Victoria

2014-01-01

The author considers combinatory play as an intersection between creativity, play, and neuroaesthetics. She discusses combinatory play as vital to the creative process in art and science, particularly with regard to the incubation of new ideas. She reviews findings from current neurobiological research and outlines the way that the brain activates…

DNA recognition by peptide nucleic acid-modified PCFs: from models to real samples

NASA Astrophysics Data System (ADS)

Selleri, S.; Coscelli, E.; Poli, F.; Passaro, D.; Cucinotta, A.; Lantano, C.; Corradini, R.; Marchelli, R.

2010-04-01

The increased concern, emerged in the last few years, on food products safety has stimulated the research on new techniques for traceability of raw food materials. DNA analysis is one of the most powerful tools for the certification of food quality, and it is presently performed through the polymerase chain reaction technique. Photonic crystal fibers, due to the presence of an array of air holes running along their length, can be exploited for performing DNA recognition by derivatizing hole surfaces and checking hybridization of complementary nucledotide chains in the sample. In this paper the application of a suspended core photonic crystal fiber in the recognition of DNA sequences is discussed. The fiber is characterized in terms of electromagnetic properties by means of a full-vector modal solver based on the finite element method. Then, the performances of the fiber in the recognition of mall synthetic oligonucleotides are discussed, together with a test of the possibility to extend this recognition to samples of DNA of applicative interest, such as olive leaves.

Combinatorial genetic perturbation to refine metabolic circuits for producing biofuels and biochemicals.

PubMed

Kim, Hyo Jin; Turner, Timothy Lee; Jin, Yong-Su

2013-11-01

Recent advances in metabolic engineering have enabled microbial factories to compete with conventional processes for producing fuels and chemicals. Both rational and combinatorial approaches coupled with synthetic and systematic tools play central roles in metabolic engineering to create and improve a selected microbial phenotype. Compared to knowledge-based rational approaches, combinatorial approaches exploiting biological diversity and high-throughput screening have been demonstrated as more effective tools for improving various phenotypes of interest. In particular, identification of unprecedented targets to rewire metabolic circuits for maximizing yield and productivity of a target chemical has been made possible. This review highlights general principles and the features of the combinatorial approaches using various libraries to implement desired phenotypes for strain improvement. In addition, recent applications that harnessed the combinatorial approaches to produce biofuels and biochemicals will be discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

Tumor-targeting peptides from combinatorial libraries.

PubMed

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

2017-02-01

Cancer is one of the major and leading causes of death worldwide. Two of the greatest challenges in fighting 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. Copyright © 2017. Published by Elsevier B.V.

Whole grain rice flavor asssociated with assorted bran colors

USDA-ARS?s Scientific Manuscript database

Recognition of the health benefits of whole grain and pigmented bran rice has resulted in their increased consumption. The bran contributes fiber, minerals, vitamins, and an array of phytonutrients to the diet. Understanding flavor differences arising from bran pigmentation helps consumers choose ...

Optical demodulation system for digitally encoded suspension array in fluoroimmunoassay

NASA Astrophysics Data System (ADS)

He, Qinghua; Li, Dongmei; He, Yonghong; Guan, Tian; Zhang, Yilong; Shen, Zhiyuan; Chen, Xuejing; Liu, Siyu; Lu, Bangrong; Ji, Yanhong

2017-09-01

A laser-induced breakdown spectroscopy and fluorescence spectroscopy-coupled optical system is reported to demodulate digitally encoded suspension array in fluoroimmunoassay. It takes advantage of the plasma emissions of assembled elemental materials to digitally decode the suspension array, providing a more stable and accurate recognition to target biomolecules. By separating the decoding procedure of suspension array and adsorption quantity calculation of biomolecules into two independent channels, the cross talk between decoding and label signals in traditional methods had been successfully avoided, which promoted the accuracy of both processes and realized more sensitive quantitative detection of target biomolecules. We carried a multiplexed detection of several types of anti-IgG to verify the quantitative analysis performance of the system. A limit of detection of 1.48×10-10 M was achieved, demonstrating the detection sensitivity of the optical demodulation system.

The method of parallel-hierarchical transformation for rapid recognition of dynamic images using GPGPU technology

NASA Astrophysics Data System (ADS)

Timchenko, Leonid; Yarovyi, Andrii; Kokriatskaya, Nataliya; Nakonechna, Svitlana; Abramenko, Ludmila; Ławicki, Tomasz; Popiel, Piotr; Yesmakhanova, Laura

2016-09-01

The paper presents a method of parallel-hierarchical transformations for rapid recognition of dynamic images using GPU technology. Direct parallel-hierarchical transformations based on cluster CPU-and GPU-oriented hardware platform. Mathematic models of training of the parallel hierarchical (PH) network for the transformation are developed, as well as a training method of the PH network for recognition of dynamic images. This research is most topical for problems on organizing high-performance computations of super large arrays of information designed to implement multi-stage sensing and processing as well as compaction and recognition of data in the informational structures and computer devices. This method has such advantages as high performance through the use of recent advances in parallelization, possibility to work with images of ultra dimension, ease of scaling in case of changing the number of nodes in the cluster, auto scan of local network to detect compute nodes.

Morphological Constraints on Cerebellar Granule Cell Combinatorial Diversity.

PubMed

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. Despite the centrality of these theories to cerebellar physiology, the degree of expansion supported by anatomically realistic patterns of inputs is unknown. Using modeling and anatomy, we show that realistic input patterns constrain combinatorial diversity by producing redundant combinations, which nevertheless could support temporal diversification of like combinations, suitable for learned timing. Our study suggests a neural substrate for producing high levels of both combinatorial and temporal diversity in the granule cell layer. Copyright © 2017 the authors 0270-6474/17/3712153-14$15.00/0.

Simple Learned Weighted Sums of Inferior Temporal Neuronal Firing Rates Accurately Predict Human Core Object Recognition Performance.

PubMed

Majaj, Najib J; Hong, Ha; Solomon, Ethan A; DiCarlo, James J

2015-09-30

To go beyond qualitative models of the biological substrate of object recognition, we ask: can a single ventral stream neuronal linking hypothesis quantitatively account for core object recognition performance over a broad range of tasks? We measured human performance in 64 object recognition tests using thousands of challenging images that explore shape similarity and identity preserving object variation. We then used multielectrode arrays to measure neuronal population responses to those same images in visual areas V4 and inferior temporal (IT) cortex of monkeys and simulated V1 population responses. We tested leading candidate linking hypotheses and control hypotheses, each postulating how ventral stream neuronal responses underlie object recognition behavior. Specifically, for each hypothesis, we computed the predicted performance on the 64 tests and compared it with the measured pattern of human performance. All tested hypotheses based on low- and mid-level visually evoked activity (pixels, V1, and V4) were very poor predictors of the human behavioral pattern. However, simple learned weighted sums of distributed average IT firing rates exactly predicted the behavioral pattern. More elaborate linking hypotheses relying on IT trial-by-trial correlational structure, finer IT temporal codes, or ones that strictly respect the known spatial substructures of IT ("face patches") did not improve predictive power. Although these results do not reject those more elaborate hypotheses, they suggest a simple, sufficient quantitative model: each object recognition task is learned from the spatially distributed mean firing rates (100 ms) of ∼60,000 IT neurons and is executed as a simple weighted sum of those firing rates. Significance statement: We sought to go beyond qualitative models of visual object recognition and determine whether a single neuronal linking hypothesis can quantitatively account for core object recognition behavior. To achieve this, we designed a database of images for evaluating object recognition performance. We used multielectrode arrays to characterize hundreds of neurons in the visual ventral stream of nonhuman primates and measured the object recognition performance of >100 human observers. Remarkably, we found that simple learned weighted sums of firing rates of neurons in monkey inferior temporal (IT) cortex accurately predicted human performance. Although previous work led us to expect that IT would outperform V4, we were surprised by the quantitative precision with which simple IT-based linking hypotheses accounted for human behavior. Copyright © 2015 the authors 0270-6474/15/3513402-17$15.00/0.

The multi-zinc finger protein ZNF217 contacts DNA through a two-finger domain.

PubMed

Nunez, Noelia; Clifton, Molly M K; Funnell, Alister P W; Artuz, Crisbel; Hallal, Samantha; Quinlan, Kate G R; Font, Josep; Vandevenne, Marylène; Setiyaputra, Surya; Pearson, Richard C M; Mackay, Joel P; Crossley, Merlin

2011-11-04

Classical C2H2 zinc finger proteins are among the most abundant transcription factors found in eukaryotes, and the mechanisms through which they recognize their target genes have been extensively investigated. In general, a tandem array of three fingers separated by characteristic TGERP links is required for sequence-specific DNA recognition. Nevertheless, a significant number of zinc finger proteins do not contain a hallmark three-finger array of this type, raising the question of whether and how they contact DNA. We have examined the multi-finger protein ZNF217, which contains eight classical zinc fingers. ZNF217 is implicated as an oncogene and in repressing the E-cadherin gene. We show that two of its zinc fingers, 6 and 7, can mediate contacts with DNA. We examine its putative recognition site in the E-cadherin promoter and demonstrate that this is a suboptimal site. NMR analysis and mutagenesis is used to define the DNA binding surface of ZNF217, and we examine the specificity of the DNA binding activity using fluorescence anisotropy titrations. Finally, sequence analysis reveals that a variety of multi-finger proteins also contain two-finger units, and our data support the idea that these may constitute a distinct subclass of DNA recognition motif.

The Multi-zinc Finger Protein ZNF217 Contacts DNA through a Two-finger Domain*

PubMed Central

Nunez, Noelia; Clifton, Molly M. K.; Funnell, Alister P. W.; Artuz, Crisbel; Hallal, Samantha; Quinlan, Kate G. R.; Font, Josep; Vandevenne, Marylène; Setiyaputra, Surya; Pearson, Richard C. M.; Mackay, Joel P.; Crossley, Merlin

2011-01-01

Classical C2H2 zinc finger proteins are among the most abundant transcription factors found in eukaryotes, and the mechanisms through which they recognize their target genes have been extensively investigated. In general, a tandem array of three fingers separated by characteristic TGERP links is required for sequence-specific DNA recognition. Nevertheless, a significant number of zinc finger proteins do not contain a hallmark three-finger array of this type, raising the question of whether and how they contact DNA. We have examined the multi-finger protein ZNF217, which contains eight classical zinc fingers. ZNF217 is implicated as an oncogene and in repressing the E-cadherin gene. We show that two of its zinc fingers, 6 and 7, can mediate contacts with DNA. We examine its putative recognition site in the E-cadherin promoter and demonstrate that this is a suboptimal site. NMR analysis and mutagenesis is used to define the DNA binding surface of ZNF217, and we examine the specificity of the DNA binding activity using fluorescence anisotropy titrations. Finally, sequence analysis reveals that a variety of multi-finger proteins also contain two-finger units, and our data support the idea that these may constitute a distinct subclass of DNA recognition motif. PMID:21908891

Application of computer assisted combinatorial chemistry in antivirial, antimalarial and anticancer agents design

NASA Astrophysics Data System (ADS)

Burello, E.; Bologa, C.; Frecer, V.; Miertus, S.

Combinatorial chemistry and technologies have been developed to a stage where synthetic schemes are available for generation of a large variety of organic molecules. The innovative concept of combinatorial design assumes that screening of a large and diverse library of compounds will increase the probability of finding an active analogue among the compounds tested. Since the rate at which libraries are screened for activity currently constitutes a limitation to the use of combinatorial technologies, it is important to be selective about the number of compounds to be synthesized. Early experience with combinatorial chemistry indicated that chemical diversity alone did not result in a significant increase in the number of generated lead compounds. Emphasis has therefore been increasingly put on the use of computer assisted combinatorial chemical techniques. Computational methods are valuable in the design of virtual libraries of molecular models. Selection strategies based on computed physicochemical properties of the models or of a target compound are introduced to reduce the time and costs of library synthesis and screening. In addition, computational structure-based library focusing methods can be used to perform in silico screening of the activity of compounds against a target receptor by docking the ligands into the receptor model. Three case studies are discussed dealing with the design of targeted combinatorial libraries of inhibitors of HIV-1 protease, P. falciparum plasmepsin and human urokinase as potential antivirial, antimalarial and anticancer drugs. These illustrate library focusing strategies.

Experience improves feature extraction in Drosophila.

PubMed

Peng, Yueqing; Xi, Wang; Zhang, Wei; Zhang, Ke; Guo, Aike

2007-05-09

Previous exposure to a pattern in the visual scene can enhance subsequent recognition of that pattern in many species from honeybees to humans. However, whether previous experience with a visual feature of an object, such as color or shape, can also facilitate later recognition of that particular feature from multiple visual features is largely unknown. Visual feature extraction is the ability to select the key component from multiple visual features. Using a visual flight simulator, we designed a novel protocol for visual feature extraction to investigate the effects of previous experience on visual reinforcement learning in Drosophila. We found that, after conditioning with a visual feature of objects among combinatorial shape-color features, wild-type flies exhibited poor ability to extract the correct visual feature. However, the ability for visual feature extraction was greatly enhanced in flies trained previously with that visual feature alone. Moreover, we demonstrated that flies might possess the ability to extract the abstract category of "shape" but not a particular shape. Finally, this experience-dependent feature extraction is absent in flies with defective MBs, one of the central brain structures in Drosophila. Our results indicate that previous experience can enhance visual feature extraction in Drosophila and that MBs are required for this experience-dependent visual cognition.

Tectonic reversal of the western Doruneh Fault System: Implications for Central Asian tectonics

NASA Astrophysics Data System (ADS)

Javadi, Hamid Reza; Esterabi Ashtiani, Marzieh; Guest, Bernard; Yassaghi, Ali; Ghassemi, Mohammad Reza; Shahpasandzadeh, Majid; Naeimi, Amir

2015-10-01

The left-lateral Doruneh Fault System (DFS) bounds the north margin of the Central Iranian microplate and has played an important role in the structural evolution of the Turkish-Iranian plateau. The western termination of the DFS is a sinistral synthetic branch fault array that shows clear kinematic evidence of having undergone recent slip sense inversion from a dextral array to a sinistral array in the latest Neogene or earliest Quaternary. Similarly, kinematic evidence from the Anarak Metamorphic complex suggests that this complex initially developed at a transpressive left-stepping termination of the DFS and that it was inverted in the latest Neogene to a transtensional fault termination. The recognition that the DFS and other faults in NE Iran were inverted from dextral to sinistral strike slip in the latest Neogene and the likely connection between the DFS and the Herat Fault of Afghanistan suggests that prior to the latest Miocene, all of the north Iranian and northern Afghan ranges were part of a distributed dextral fault network that extended from the west Himalayan syntaxes to the western Alborz. Also, the recognition that regional slip sense inversion occurred across northern and northeastern Iran after the latest Miocene invalidates tectonic models that extrapolate Pleistocene to recent fault slip kinematics and rates back beyond this time.

Microbioreactor Arrays for Full Factorial Screening of Exogenous and Paracrine Factors in Human Embryonic Stem Cell Differentiation

PubMed Central

Titmarsh, Drew M.; Hudson, James E.; Hidalgo, Alejandro; Elefanty, Andrew G.; Stanley, Edouard G.; Wolvetang, Ernst J.; Cooper-White, Justin J.

2012-01-01

Timed exposure of pluripotent stem cell cultures to exogenous molecules is widely used to drive differentiation towards desired cell lineages. However, screening differentiation conditions in conventional static cultures can become impractical in large parameter spaces, and is intrinsically limited by poor spatiotemporal control of the microenvironment that also makes it impossible to determine whether exogenous factors act directly or through paracrine-dependent mechanisms. We detail here the development of a continuous flow microbioreactor array platform that combines full-factorial multiplexing of input factors with progressive accumulation of paracrine factors through serially-connected culture chambers, and further, the use of this system to explore the combinatorial parameter space of both exogenous and paracrine factors involved in human embryonic stem cell (hESC) differentiation to a MIXL1-GFP+ primitive streak-like population. We show that well known inducers of primitive streak (BMP, Activin and Wnt signals) do not simply act directly on hESC to induce MIXL1 expression, but that this requires accumulation of surplus, endogenous factors; and, that conditioned medium or FGF-2 supplementation is able to offset this. Our approach further reveals the presence of a paracrine, negative feedback loop to the MIXL1-GFP+ population, which can be overcome with GSK-3β inhibitors (BIO or CHIR99021), implicating secreted Wnt inhibitory signals such as DKKs and sFRPs as candidate effectors. Importantly, modulating paracrine effects identified in microbioreactor arrays by supplementing FGF-2 and CHIR in conventional static culture vessels resulted in improved differentiation outcomes. We therefore demonstrate that this microbioreactor array platform uniquely enables the identification and decoding of complex soluble factor signalling hierarchies, and that this not only challenges prevailing strategies for extrinsic control of hESC differentiation, but also is translatable to conventional culture systems. PMID:23300662

Invited: Advances Toward Practical Detection of Trace Chemical Hazards with Solid State Microarray Devices

NASA Astrophysics Data System (ADS)

Raman, Barani; Meier, Douglas; Shenoy, Rupa; Benkstein, Kurt; Semancik, Steve

2011-09-01

We describe progress on an array-based microsensor approach employed for detecting trace levels of toxic industrial chemicals (TICs) in air-based backgrounds with varied levels of humidity, and with occasional introduction of aggressive interferents. Our MEMS microhotplate arrays are populated with multiple chemiresistive sensing materials, and all elements are programmed to go through extensive temperature cycling over repetitive cycles with lengths of approximately 20 s. Under such operation, analytically-rich data streams are produced containing the required information for target recognition.

Odor Sensing System Using Preconcentrator with Variable Temperature

DOE Office of Scientific and Technical Information (OSTI.GOV)

Isaka, Y; Nakamoto, Takamichi; Moriizumi, T

1999-01-01

An odor sensing system using QCM gas sensor array and pattern recognition technique is useful to identify various kinds of odors. A preconcentrator with variable temperature is promising to obtain further pattern separation after the appropriate temperature changes, whereas it has been so far used to enhance sensor sensitivity. After the preconcentrator collects the vapors, it is heated so that they can be thermally desorbed. The combination of the preconcentrator with the sensor array enhances the capability of discrimination among vapors since their desorption temperatures depend upon vapor kinds.

Systolic Processor Array For Recognition Of Spectra

NASA Technical Reports Server (NTRS)

Chow, Edward T.; Peterson, John C.

1995-01-01

Spectral signatures of materials detected and identified quickly. Spectral Analysis Systolic Processor Array (SPA2) relatively inexpensive and satisfies need to analyze large, complex volume of multispectral data generated by imaging spectrometers to extract desired information: computational performance needed to do this in real time exceeds that of current supercomputers. Locates highly similar segments or contiguous subsegments in two different spectra at time. Compares sampled spectra from instruments with data base of spectral signatures of known materials. Computes and reports scores that express degrees of similarity between sampled and data-base spectra.

Nanostructured Ti-Ta thin films synthesized by combinatorial glancing angle sputter deposition

NASA Astrophysics Data System (ADS)

Motemani, Yahya; Khare, Chinmay; Savan, Alan; Hans, Michael; Paulsen, Alexander; Frenzel, Jan; Somsen, Christoph; Mücklich, Frank; Eggeler, Gunther; Ludwig, Alfred

2016-12-01

Ti-Ta alloys are attractive materials for applications in actuators as well as biomedical implants. When fabricated as thin films, these alloys can potentially be employed as microactuators, components for micro-implantable devices and coatings on surgical implants. In this study, Ti100-x Ta x (x = 21, 30) nanocolumnar thin films are fabricated by glancing angle deposition (GLAD) at room temperature using Ti73Ta27 and Ta sputter targets. Crystal structure, morphology and microstructure of the nanostructured thin films are systematically investigated by XRD, SEM and TEM, respectively. Nanocolumns of ˜150-160 nm in width are oriented perpendicular to the substrate for both Ti79Ta21 and Ti70Ta30 compositions. The disordered α″ martensite phase with orthorhombic structure is formed in room temperature as-deposited thin films. The columns are found to be elongated small single crystals which are aligned perpendicular to the (20\\bar{4}) and (204) planes of α″ martensite, indicating that the films’ growth orientation is mainly dominated by these crystallographic planes. Laser pre-patterned substrates are utilized to obtain periodic nanocolumnar arrays. The differences in seed pattern, and inter-seed distances lead to growth of multi-level porous nanostructures. Using a unique sputter deposition geometry consisting of Ti73Ta27 and Ta sputter sources, a nanocolumnar Ti-Ta materials library was fabricated on a static substrate by a co-deposition process (combinatorial-GLAD approach). In this library, a composition spread developed between Ti72.8Ta27.2 and Ti64.4Ta35.6, as confirmed by high-throughput EDX analysis. The morphology over the materials library varies from well-isolated nanocolumns to fan-like nanocolumnar structures. The influence of two sputter sources is investigated by studying the resulting column angle on the materials library. The presented nanostructuring methods including the use of the GLAD technique along with pre-patterning and a combinatorial materials library fabrication strategy offer a promising technological approach for investigating Ti-Ta thin films for a range of applications. The proposed approaches can be similarly implemented for other materials systems which can benefit from the formation of a nanocolumnar morphology.

Cambridge Healthtech Institute's Third Annual Conference on Lab-on-a-Chip and Microarrays. 22-24 January 2001, Zurich, Switzerland.

PubMed

Jain, K K

2001-02-01

Cambridge Healthtech Institute's Third Annual Conference on Lab-on-a-Chip and Microarray technology covered the latest advances in this technology and applications in life sciences. Highlights of the meetings are reported briefly with emphasis on applications in genomics, drug discovery and molecular diagnostics. There was an emphasis on microfluidics because of the wide applications in laboratory and drug discovery. The lab-on-a-chip provides the facilities of a complete laboratory in a hand-held miniature device. Several microarray systems have been used for hybridisation and detection techniques. Oligonucleotide scanning arrays provide a versatile tool for the analysis of nucleic acid interactions and provide a platform for improving the array-based methods for investigation of antisense therapeutics. A method for analysing combinatorial DNA arrays using oligonucleotide-modified gold nanoparticle probes and a conventional scanner has considerable potential in molecular diagnostics. Various applications of microarray technology for high-throughput screening in drug discovery and single nucleotide polymorphisms (SNP) analysis were discussed. Protein chips have important applications in proteomics. With the considerable amount of data generated by the different technologies using microarrays, it is obvious that the reading of the information and its interpretation and management through the use of bioinformatics is essential. Various techniques for data analysis were presented. Biochip and microarray technology has an essential role to play in the evolving trends in healthcare, which integrate diagnosis with prevention/treatment and emphasise personalised medicines.

Combinatorial chemistry has matured in the last three decades: dedicated to Professor Árpád Furka on the occasion of his 80th birthday.

PubMed

Dibó, Gábor

2012-02-01

Combinatorial chemistry was introduced in the 1980s. It provided the possibility to produce new compounds in practically unlimited number. New strategies and technologies have also been developed that made it possible to screen very large number of compounds and to identify useful components in mixtures containing millions of different substances. This dramatically changed the drug discovery process and the way of thinking of synthetic chemists. In addition, combinatorial strategies became useful in areas such as pharmaceutical research, agrochemistry, catalyst design, and materials research. Prof. Árpád Furka is one of the pioneers of combinatorial chemistry.

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

PubMed

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.

A label-free optical biosensor for serotyping "unknown" influenza viruses

NASA Astrophysics Data System (ADS)

Zhang, Hanyuan; Henry Dunand, Carole; Wilson, Patrick; Miller, Benjamin L.

2016-05-01

The ability to accurately classify influenza viruses is critical to understanding patterns of infection, vaccine efficacy, and to the process of developing new vaccines. Unfortunately, this task is hampered both by the virus' ability to undergo antigenic drift and shift (rendering it a "previously unknown" strain), and by technological limitations. In an effort to overcome these challenges, we have developed a label-free human monoclonal antibody array for flu serology, using a pattern recognition approach to assign virus serotype. The array is built on the Arrayed Imaging Reflectometry (AIR) platform. AIR relies on the creation of a near-perfect antireflective condition on the surface of a silicon chip. When this antireflective condition is perturbed because of binding to an antibody spot (or other immobilized probe molecule), binding may be sensitively and quantitatively detected as an increase in reflected light. We describe fabrication and characterization of the array, and preliminary testing with isolated influenza hemagglutinin. We anticipate that this approach may be extended to other viruses by expansion of the array.

Phospholipid arrays on porous polymer coatings generated by micro-contact spotting

PubMed Central

de Freitas, Monica; Tröster, Lea-Marie; Jochum, Tobias; Levkin, Pavel A; Hirtz, Michael; Fuchs, Harald

2017-01-01

Nanoporous poly(2-hydroxyethyl methacrylate-co-ethylene dimethacrylate) (HEMA-EDMA) is used as a 3D mesh for spotting lipid arrays. Its porous structure is an ideal matrix for lipid ink to infiltrate, resulting in higher fluorescent signal intensity as compared to similar arrays on strictly 2D substrates like glass. The embedded lipid arrays show high stability against washing steps, while still being accessible for protein and antibody binding. To characterize binding to polymer-embedded lipids we have applied Streptavidin as well as biologically important biotinylated androgen receptor binding onto 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-(cap biotinyl) (Biotinyl Cap PE) and anti-DNP IgE recognition of 2,4-dinitrophenyl[1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[6-[(2,4-dinitrophenyl)amino]hexanoyl] (DNP)] antigen. This approach adds lipid arrays to the range of HEMA polymer applications and makes this solid substrate a very attractive platform for a variety of bio-applications. PMID:28487815

Deciphering the role of DC subsets in MCMV infection to better understand immune protection against viral infections

PubMed Central

Alexandre, Yannick O.; Cocita, Clément D.; Ghilas, Sonia; Dalod, Marc

2014-01-01

Infection of mice with murine cytomegalovirus (MCMV) recapitulates many physiopathological characteristics of human CMV infection and enables studying the interactions between a virus and its natural host. Dendritic cells (DC) are mononuclear phagocytes linking innate and adaptive immunity which are both necessary for MCMV control. DC are critical for the induction of cellular immunity because they are uniquely efficient for the activation of naïve T cells during their first encounter with a pathogen. DC are equipped with a variety of innate immune recognition receptors (I2R2) allowing them to detect pathogens or infections and to engulf molecules, microorganisms or cellular debris. The combinatorial engagement of I2R2 during infections controls DC maturation and shapes their response in terms of cytokine production, activation of natural killer (NK) cells and functional polarization of T cells. Several DC subsets exist which express different arrays of I2R2 and are specialized in distinct functions. The study of MCMV infection helped deciphering the physiological roles of DC subsets and their molecular regulation. It allowed the identification and first in vivo studies of mouse plasmacytoid DC which produce high level of interferons-α/β early after infection. Despite its ability to infect DC and dampen their functions, MCMV induces very robust, efficient and long-lasting CD8 T cell responses. Their priming may rely on the unique ability of uninfected XCR1+ DC to cross-present engulfed viral antigens and thus to counter MCMV interference with antigen presentation. A balance appears to have been reached during co-evolution, allowing controlled replication of the virus for horizontal spread without pathological consequences for the immunocompetent host. We will discuss the role of the interplay between the virus and DC in setting this balance, and how advancing this knowledge further could help develop better vaccines against other intracellular infectious agents. PMID:25120535

Dynamical principles in neuroscience

NASA Astrophysics Data System (ADS)

Rabinovich, Mikhail I.; Varona, Pablo; Selverston, Allen I.; Abarbanel, Henry D. I.

2006-10-01

Dynamical modeling of neural systems and brain functions has a history of success over the last half century. This includes, for example, the explanation and prediction of some features of neural rhythmic behaviors. Many interesting dynamical models of learning and memory based on physiological experiments have been suggested over the last two decades. Dynamical models even of consciousness now exist. Usually these models and results are based on traditional approaches and paradigms of nonlinear dynamics including dynamical chaos. Neural systems are, however, an unusual subject for nonlinear dynamics for several reasons: (i) Even the simplest neural network, with only a few neurons and synaptic connections, has an enormous number of variables and control parameters. These make neural systems adaptive and flexible, and are critical to their biological function. (ii) In contrast to traditional physical systems described by well-known basic principles, first principles governing the dynamics of neural systems are unknown. (iii) Many different neural systems exhibit similar dynamics despite having different architectures and different levels of complexity. (iv) The network architecture and connection strengths are usually not known in detail and therefore the dynamical analysis must, in some sense, be probabilistic. (v) Since nervous systems are able to organize behavior based on sensory inputs, the dynamical modeling of these systems has to explain the transformation of temporal information into combinatorial or combinatorial-temporal codes, and vice versa, for memory and recognition. In this review these problems are discussed in the context of addressing the stimulating questions: What can neuroscience learn from nonlinear dynamics, and what can nonlinear dynamics learn from neuroscience?

Dynamical principles in neuroscience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rabinovich, Mikhail I.; Varona, Pablo; Selverston, Allen I.

Dynamical modeling of neural systems and brain functions has a history of success over the last half century. This includes, for example, the explanation and prediction of some features of neural rhythmic behaviors. Many interesting dynamical models of learning and memory based on physiological experiments have been suggested over the last two decades. Dynamical models even of consciousness now exist. Usually these models and results are based on traditional approaches and paradigms of nonlinear dynamics including dynamical chaos. Neural systems are, however, an unusual subject for nonlinear dynamics for several reasons: (i) Even the simplest neural network, with only amore » few neurons and synaptic connections, has an enormous number of variables and control parameters. These make neural systems adaptive and flexible, and are critical to their biological function. (ii) In contrast to traditional physical systems described by well-known basic principles, first principles governing the dynamics of neural systems are unknown. (iii) Many different neural systems exhibit similar dynamics despite having different architectures and different levels of complexity. (iv) The network architecture and connection strengths are usually not known in detail and therefore the dynamical analysis must, in some sense, be probabilistic. (v) Since nervous systems are able to organize behavior based on sensory inputs, the dynamical modeling of these systems has to explain the transformation of temporal information into combinatorial or combinatorial-temporal codes, and vice versa, for memory and recognition. In this review these problems are discussed in the context of addressing the stimulating questions: What can neuroscience learn from nonlinear dynamics, and what can nonlinear dynamics learn from neuroscience?.« less

Selective host molecules obtained by dynamic adaptive chemistry.

PubMed

Matache, Mihaela; Bogdan, Elena; Hădade, Niculina D

2014-02-17

Up till 20 years ago, in order to endow molecules with function there were two mainstream lines of thought. One was to rationally design the positioning of chemical functionalities within candidate molecules, followed by an iterative synthesis-optimization process. The second was the use of a "brutal force" approach of combinatorial chemistry coupled with advanced screening for function. Although both methods provided important results, "rational design" often resulted in time-consuming efforts of modeling and synthesis only to find that the candidate molecule was not performing the designed job. "Combinatorial chemistry" suffered from a fundamental limitation related to the focusing of the libraries employed, often using lead compounds that limit its scope. Dynamic constitutional chemistry has developed as a combination of the two approaches above. Through the rational use of reversible chemical bonds together with a large plethora of precursor libraries, one is now able to build functional structures, ranging from quite simple molecules up to large polymeric structures. Thus, by introduction of the dynamic component within the molecular recognition processes, a new perspective of deciphering the world of the molecular events has aroused together with a new field of chemistry. Since its birth dynamic constitutional chemistry has continuously gained attention, in particular due to its ability to easily create from scratch outstanding molecular structures as well as the addition of adaptive features. The fundamental concepts defining the dynamic constitutional chemistry have been continuously extended to currently place it at the intersection between the supramolecular chemistry and newly defined adaptive chemistry, a pivotal feature towards evolutive chemistry. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Analyte-Responsive Hydrogels: Intelligent Materials for Biosensing and Drug Delivery.

PubMed

Culver, Heidi R; Clegg, John R; Peppas, Nicholas A

2017-02-21

Nature has mastered the art of molecular recognition. For example, using synergistic non-covalent interactions, proteins can distinguish between molecules and bind a partner with incredible affinity and specificity. Scientists have developed, and continue to develop, techniques to investigate and better understand molecular recognition. As a consequence, analyte-responsive hydrogels that mimic these recognitive processes have emerged as a class of intelligent materials. These materials are unique not only in the type of analyte to which they respond but also in how molecular recognition is achieved and how the hydrogel responds to the analyte. Traditional intelligent hydrogels can respond to environmental cues such as pH, temperature, and ionic strength. The functional monomers used to make these hydrogels can be varied to achieve responsive behavior. For analyte-responsive hydrogels, molecular recognition can also be achieved by incorporating biomolecules with inherent molecular recognition properties (e.g., nucleic acids, peptides, enzymes, etc.) into the polymer network. Furthermore, in addition to typical swelling/syneresis responses, these materials exhibit unique responsive behaviors, such as gel assembly or disassembly, upon interaction with the target analyte. With the diverse tools available for molecular recognition and the ability to generate unique responsive behaviors, analyte-responsive hydrogels have found great utility in a wide range of applications. In this Account, we discuss strategies for making four different classes of analyte-responsive hydrogels, specifically, non-imprinted, molecularly imprinted, biomolecule-containing, and enzymatically responsive hydrogels. Then we explore how these materials have been incorporated into sensors and drug delivery systems, highlighting examples that demonstrate the versatility of these materials. For example, in addition to the molecular recognition properties of analyte-responsive hydrogels, the physicochemical changes that are induced upon analyte binding can be exploited to generate a detectable signal for sensing applications. As research in this area has grown, a number of creative approaches for improving the selectivity and sensitivity (i.e., detection limit) of these sensors have emerged. For applications in drug delivery systems, therapeutic release can be triggered by competitive molecular interactions or physicochemical changes in the network. Additionally, including degradable units within the network can enable sustained and responsive therapeutic release. Several exciting examples exploiting the analyte-responsive behavior of hydrogels for the treatment of cancer, diabetes, and irritable bowel syndrome are discussed in detail. We expect that creative and combinatorial approaches used in the design of analyte-responsive hydrogels will continue to yield materials with great potential in the fields of sensing and drug delivery.

Low power, lightweight vapor sensing using arrays of conducting polymer composite chemically-sensitive resistors

NASA Technical Reports Server (NTRS)

Ryan, M. A.; Lewis, N. S.

2001-01-01

Arrays of broadly responsive vapor detectors can be used to detect, identify, and quantify vapors and vapor mixtures. One implementation of this strategy involves the use of arrays of chemically-sensitive resistors made from conducting polymer composites. Sorption of an analyte into the polymer composite detector leads to swelling of the film material. The swelling is in turn transduced into a change in electrical resistance because the detector films consist of polymers filled with conducting particles such as carbon black. The differential sorption, and thus differential swelling, of an analyte into each polymer composite in the array produces a unique pattern for each different analyte of interest, Pattern recognition algorithms are then used to analyze the multivariate data arising from the responses of such a detector array. Chiral detector films can provide differential detection of the presence of certain chiral organic vapor analytes. Aspects of the spaceflight qualification and deployment of such a detector array, along with its performance for certain analytes of interest in manned life support applications, are reviewed and summarized in this article.

Systematic Identification of Combinatorial Drivers and Targets in Cancer Cell Lines

PubMed Central

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. PMID:23577104

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

PubMed

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.

An evaluation of methods for estimating the number of local optima in combinatorial optimization problems.

PubMed

Hernando, Leticia; Mendiburu, Alexander; Lozano, Jose A

2013-01-01

The solution of many combinatorial optimization problems is carried out by metaheuristics, which generally make use of local search algorithms. These algorithms use some kind of neighborhood structure over the search space. The performance of the algorithms strongly depends on the properties that the neighborhood imposes on the search space. One of these properties is the number of local optima. Given an instance of a combinatorial optimization problem and a neighborhood, the estimation of the number of local optima can help not only to measure the complexity of the instance, but also to choose the most convenient neighborhood to solve it. In this paper we review and evaluate several methods to estimate the number of local optima in combinatorial optimization problems. The methods reviewed not only come from the combinatorial optimization literature, but also from the statistical literature. A thorough evaluation in synthetic as well as real problems is given. We conclude by providing recommendations of methods for several scenarios.

Combinatorial materials approach to accelerate materials discovery for transportation (Conference Presentation)

NASA Astrophysics Data System (ADS)

Tong, Wei

2017-04-01

Combinatorial material research offers fast and efficient solutions to identify promising and advanced materials. It has revolutionized the pharmaceutical industry and now is being applied to accelerate the discovery of other new compounds, e.g. superconductors, luminescent materials, catalysts etc. Differing from the traditional trial-and-error process, this approach allows for the synthesis of a large number of compositionally diverse compounds by varying the combinations of the components and adjusting the ratios. It largely reduces the cost of single-sample synthesis/characterization, along with the turnaround time in the material discovery process, therefore, could dramatically change the existing paradigm for discovering and commercializing new materials. This talk outlines the use of combinatorial materials approach in the material discovery in transportation sector. It covers the general introduction to the combinatorial material concept, state of art for its application in energy-related research. At the end, LBNL capabilities in combinatorial materials synthesis and high throughput characterization that are applicable for material discovery research will be highlighted.

Tunable Gas Sensing Gels by Cooperative Assembly

PubMed Central

Hussain, Abid; Semeano, Ana T. S.; Palma, Susana I. C. J.; Pina, Ana S.; Almeida, José; Medrado, Bárbara F.; Pádua, Ana C. C. S.; Carvalho, Ana L.; Dionísio, Madalena; Li, Rosamaria W. C.; Gamboa, Hugo; Ulijn, Rein V.; Gruber, Jonas; Roque, Ana C. A.

2017-01-01

The cooperative assembly of biopolymers and small molecules can yield functional materials with precisely tunable properties. Here, the fabrication, characterization, and use of multicomponent hybrid gels as selective gas sensors are reported. The gels are composed of liquid crystal droplets self-assembled in the presence of ionic liquids, which further coassemble with biopolymers to form stable matrices. Each individual component can be varied and acts cooperatively to tune gels’ structure and function. The unique molecular environment in hybrid gels is explored for supramolecular recognition of volatile compounds. Gels with distinct compositions are used as optical and electrical gas sensors, yielding a combinatorial response conceptually mimicking olfactory biological systems, and tested to distinguish volatile organic compounds and to quantify ethanol in automotive fuel. The gel response is rapid, reversible, and reproducible. These robust, versatile, modular, pliant electro-optical soft materials possess new possibilities in sensing triggered by chemical and physical stimuli. PMID:28747856

Structural basis for precursor protein-directed ribosomal peptide macrocyclization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Kunhua; Condurso, Heather L.; Li, Gengnan

Macrocyclization is a common feature of natural product biosynthetic pathways including the diverse family of ribosomal peptides. Microviridins are architecturally complex cyanobacterial ribosomal peptides that target proteases with potent reversible inhibition. The product structure is constructed via three macrocyclizations catalyzed sequentially by two members of the ATP-grasp family, a unique strategy for ribosomal peptide macrocyclization. Here we describe in detail the structural basis for the enzyme-catalyzed macrocyclizations in the microviridin J pathway of Microcystis aeruginosa. The macrocyclases MdnC and MdnB interact with a conserved α-helix of the precursor peptide using a novel precursor-peptide recognition mechanism. The results provide insight intomore » the unique protein–protein interactions that are key to the chemistry, suggest an origin for the natural combinatorial synthesis of microviridin peptides, and provide a framework for future engineering efforts to generate designed compounds.« less

Single-carbon discrimination by selected peptides for individual detection of volatile organic compounds

NASA Astrophysics Data System (ADS)

Ju, Soomi; Lee, Ki-Young; Min, Sun-Joon; Yoo, Yong Kyoung; Hwang, Kyo Seon; Kim, Sang Kyung; Yi, Hyunjung

2015-03-01

Although volatile organic compounds (VOCs) are becoming increasingly recognized as harmful agents and potential biomarkers, selective detection of the organic targets remains a tremendous challenge. Among the materials being investigated for target recognition, peptides are attractive candidates because of their chemical robustness, divergence, and their homology to natural olfactory receptors. Using a combinatorial peptide library and either a graphitic surface or phenyl-terminated self-assembled monolayer as relevant target surfaces, we successfully selected three interesting peptides that differentiate a single carbon deviation among benzene and its analogues. The heterogeneity of the designed target surfaces provided peptides with varying affinity toward targeted molecules and generated a set of selective peptides that complemented each other. Microcantilever sensors conjugated with each peptide quantitated benzene, toluene and xylene to sub-ppm levels in real time. The selection of specific receptors for a group of volatile molecules will provide a strong foundation for general approach to individually monitoring VOCs.

A multiplexable TALE-based binary expression system for in vivo cellular interaction studies.

PubMed

Toegel, Markus; Azzam, Ghows; Lee, Eunice Y; Knapp, David J H F; Tan, Ying; Fa, Ming; Fulga, Tudor A

2017-11-21

Binary expression systems have revolutionised genetic research by enabling delivery of loss-of-function and gain-of-function transgenes with precise spatial-temporal resolution in vivo. However, at present, each existing platform relies on a defined exogenous transcription activator capable of binding a unique recognition sequence. Consequently, none of these technologies alone can be used to simultaneously target different tissues or cell types in the same organism. Here, we report a modular system based on programmable transcription activator-like effector (TALE) proteins, which enables parallel expression of multiple transgenes in spatially distinct tissues in vivo. Using endogenous enhancers coupled to TALE drivers, we demonstrate multiplexed orthogonal activation of several transgenes carrying cognate variable activating sequences (VAS) in distinct neighbouring cell types of the Drosophila central nervous system. Since the number of combinatorial TALE-VAS pairs is virtually unlimited, this platform provides an experimental framework for highly complex genetic manipulation studies in vivo.

Context-dependent control of alternative splicing by RNA-binding proteins

PubMed Central

Fu, Xiang-Dong; Ares, Manuel

2015-01-01

Sequence-specific RNA-binding proteins (RBPs) bind to pre-mRNA to control alternative splicing, but it is not yet possible to read the ‘splicing code’ that dictates splicing regulation on the basis of genome sequence. Each alternative splicing event is controlled by multiple RBPs, the combined action of which creates a distribution of alternatively spliced products in a given cell type. As each cell type expresses a distinct array of RBPs, the interpretation of regulatory information on a given RNA target is exceedingly dependent on the cell type. RBPs also control each other’s functions at many levels, including by mutual modulation of their binding activities on specific regulatory RNA elements. In this Review, we describe some of the emerging rules that govern the highly context-dependent and combinatorial nature of alternative splicing regulation. PMID:25112293

Hydroelectric power plant on a paper strip.

PubMed

Das, Sankha Shuvra; Kar, Shantimoy; Anwar, Tarique; Saha, Partha; Chakraborty, Suman

2018-05-03

We exploit the combinatorial advantage of electrokinetics and tortuosity of a cellulose-based paper network on laboratory grade filter paper for the development of a simple, inexpensive, yet extremely robust (shows constant performance for 12 days) 'paper-and-pencil'-based device for energy harvesting applications. We successfully achieve harvesting of a maximum output power of ∼640 pW in a single channel, while the same is significantly improved (by ∼100 times) with the use of a multichannel microfluidic array (maximum of up to 20 channels). Furthermore, we also provide theoretical insights into the observed phenomenon and show that the experimentally predicted trends agree well with our theoretical calculations. Thus, we envisage that such ultra-low cost devices may turn out to be extremely useful in energizing analytical microdevices in resource limited settings, for instance, in extreme point of care diagnostic applications.

Template-Directed Ligation of Peptides to Oligonucleotides

NASA Technical Reports Server (NTRS)

Bruick, Richard K.; Dawson, Philip E.; Kent, Stephen BH; Usman, Nassim; Joyce, Gerald F.

1996-01-01

Synthetic oligonucleotides and peptides have enjoyed a wide range of applications in both biology and chemistry. As a consequence, oligonucleotide-peptide conjugates have received considerable attention, most notably in the development of antisense constructs with improved pharmacological properties. In addition, oligonucleotide-peptide conjugates have been used as molecular tags, in the assembly of supramolecular arrays and in the construction of encoded combinatorial libraries. To make these chimeric molecules more accessible for a broad range of investigations, we sought to develop a facile method for joining fully deprotected oligonucleotides and peptides through a stable amide bond linkage. Furthermore, we wished to make this ligation reaction addressable, enabling one to direct the ligation of specific oligonucleotide and peptide components.To confer specificity and accelerate the rate of the reaction, the ligation process was designed to be dependent on the presence of a complementary oligonucleotide template.

Recognition of computerized facial approximations by familiar assessors.

PubMed

Richard, Adam H; Monson, Keith L

2017-11-01

Studies testing the effectiveness of facial approximations typically involve groups of participants who are unfamiliar with the approximated individual(s). This limitation requires the use of photograph arrays including a picture of the subject for comparison to the facial approximation. While this practice is often necessary due to the difficulty in obtaining a group of assessors who are familiar with the approximated subject, it may not accurately simulate the thought process of the target audience (friends and family members) in comparing a mental image of the approximated subject to the facial approximation. As part of a larger process to evaluate the effectiveness and best implementation of the ReFace facial approximation software program, the rare opportunity arose to conduct a recognition study using assessors who were personally acquainted with the subjects of the approximations. ReFace facial approximations were generated based on preexisting medical scans, and co-workers of the scan donors were tested on whether they could accurately pick out the approximation of their colleague from arrays of facial approximations. Results from the study demonstrated an overall poor recognition performance (i.e., where a single choice within a pool is not enforced) for individuals who were familiar with the approximated subjects. Out of 220 recognition tests only 10.5% resulted in the assessor selecting the correct approximation (or correctly choosing not to make a selection when the array consisted only of foils), an outcome that was not significantly different from the 9% random chance rate. When allowed to select multiple approximations the assessors felt resembled the target individual, the overall sensitivity for ReFace approximations was 16.0% and the overall specificity was 81.8%. These results differ markedly from the results of a previous study using assessors who were unfamiliar with the approximated subjects. Some possible explanations for this disparity in performance were examined, and it was ultimately concluded that ReFace facial approximations may have limited effectiveness if used in the traditional way. However, some promising alternative uses are explored that may expand the utility of facial approximations for aiding in the identification of unknown human remains. Published by Elsevier B.V.

Discovery of the leinamycin family of natural products by mining actinobacterial genomes

PubMed Central

Xu, Zhengren; Guo, Zhikai; Hindra; Ma, Ming; Zhou, Hao; Gansemans, Yannick; Zhu, Xiangcheng; Huang, Yong; Zhao, Li-Xing; Jiang, Yi; Cheng, Jinhua; Van Nieuwerburgh, Filip; Suh, Joo-Won; Duan, Yanwen

2017-01-01

Nature’s ability to generate diverse natural products from simple building blocks has inspired combinatorial biosynthesis. The knowledge-based approach to combinatorial biosynthesis has allowed the production of designer analogs by rational metabolic pathway engineering. While successful, structural alterations are limited, with designer analogs often produced in compromised titers. The discovery-based approach to combinatorial biosynthesis complements the knowledge-based approach by exploring the vast combinatorial biosynthesis repertoire found in Nature. Here we showcase the discovery-based approach to combinatorial biosynthesis by targeting the domain of unknown function and cysteine lyase domain (DUF–SH) didomain, specific for sulfur incorporation from the leinamycin (LNM) biosynthetic machinery, to discover the LNM family of natural products. By mining bacterial genomes from public databases and the actinomycetes strain collection at The Scripps Research Institute, we discovered 49 potential producers that could be grouped into 18 distinct clades based on phylogenetic analysis of the DUF–SH didomains. Further analysis of the representative genomes from each of the clades identified 28 lnm-type gene clusters. Structural diversities encoded by the LNM-type biosynthetic machineries were predicted based on bioinformatics and confirmed by in vitro characterization of selected adenylation proteins and isolation and structural elucidation of the guangnanmycins and weishanmycins. These findings demonstrate the power of the discovery-based approach to combinatorial biosynthesis for natural product discovery and structural diversity and highlight Nature’s rich biosynthetic repertoire. Comparative analysis of the LNM-type biosynthetic machineries provides outstanding opportunities to dissect Nature’s biosynthetic strategies and apply these findings to combinatorial biosynthesis for natural product discovery and structural diversity. PMID:29229819

Discovery of the leinamycin family of natural products by mining actinobacterial genomes.

PubMed

Pan, Guohui; Xu, Zhengren; Guo, Zhikai; Hindra; Ma, Ming; Yang, Dong; Zhou, Hao; Gansemans, Yannick; Zhu, Xiangcheng; Huang, Yong; Zhao, Li-Xing; Jiang, Yi; Cheng, Jinhua; Van Nieuwerburgh, Filip; Suh, Joo-Won; Duan, Yanwen; Shen, Ben

2017-12-26

Nature's ability to generate diverse natural products from simple building blocks has inspired combinatorial biosynthesis. The knowledge-based approach to combinatorial biosynthesis has allowed the production of designer analogs by rational metabolic pathway engineering. While successful, structural alterations are limited, with designer analogs often produced in compromised titers. The discovery-based approach to combinatorial biosynthesis complements the knowledge-based approach by exploring the vast combinatorial biosynthesis repertoire found in Nature. Here we showcase the discovery-based approach to combinatorial biosynthesis by targeting the domain of unknown function and cysteine lyase domain (DUF-SH) didomain, specific for sulfur incorporation from the leinamycin (LNM) biosynthetic machinery, to discover the LNM family of natural products. By mining bacterial genomes from public databases and the actinomycetes strain collection at The Scripps Research Institute, we discovered 49 potential producers that could be grouped into 18 distinct clades based on phylogenetic analysis of the DUF-SH didomains. Further analysis of the representative genomes from each of the clades identified 28 lnm -type gene clusters. Structural diversities encoded by the LNM-type biosynthetic machineries were predicted based on bioinformatics and confirmed by in vitro characterization of selected adenylation proteins and isolation and structural elucidation of the guangnanmycins and weishanmycins. These findings demonstrate the power of the discovery-based approach to combinatorial biosynthesis for natural product discovery and structural diversity and highlight Nature's rich biosynthetic repertoire. Comparative analysis of the LNM-type biosynthetic machineries provides outstanding opportunities to dissect Nature's biosynthetic strategies and apply these findings to combinatorial biosynthesis for natural product discovery and structural diversity.

A fluorometric paper-based sensor array for the discrimination of heavy-metal ions.

PubMed

Feng, Liang; Li, Hui; Niu, Li-Ya; Guan, Ying-Shi; Duan, Chun-Feng; Guan, Ya-Feng; Tung, Chen-Ho; Yang, Qing-Zheng

2013-04-15

A fluorometric paper-based sensor array has been developed for the sensitive and convenient determination of seven heavy-metal ions at their wastewater discharge standard concentrations. Combining with nine cross-reactive BODIPY fluorescent indicators and array technologies-based pattern-recognition, we have obtained the discrimination capability of seven different heavy-metal ions at their wastewater discharge standard concentrations. After the immobilization of indicators and the enrichment of analytes, identification of the heavy-metal ions was readily acquired using a standard chemometric approach. Clear differentiation among heavy-metal ions as a function of concentration was also achieved, even down to 10(-7)M. A semi-quantitative estimation of the heavy-metal ion concentration was obtained by comparing color changes with a set of known concentrations. The sensor array was tentatively investigated in spiked tap water and sea water, and showed possible feasibility for real sample testing. Copyright © 2013 Elsevier B.V. All rights reserved.

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

PubMed

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 pretreatment, together with fermentation optimization, favorably improves lipid production using lignin as the carbon source. Combinatorial pretreatment integrated with fed-batch fermentation was an effective strategy to improve the bioconversion of lignin into lipids, thus facilitating lignin valorization in biorefineries.

Optimised 'on demand' protein arraying from DNA by cell free expression with the 'DNA to Protein Array' (DAPA) technology.

PubMed

Schmidt, Ronny; Cook, Elizabeth A; Kastelic, Damjana; Taussig, Michael J; Stoevesandt, Oda

2013-08-02

We have previously described a protein arraying process based on cell free expression from DNA template arrays (DNA Array to Protein Array, DAPA). Here, we have investigated the influence of different array support coatings (Ni-NTA, Epoxy, 3D-Epoxy and Polyethylene glycol methacrylate (PEGMA)). Their optimal combination yields an increased amount of detected protein and an optimised spot morphology on the resulting protein array compared to the previously published protocol. The specificity of protein capture was improved using a tag-specific capture antibody on a protein repellent surface coating. The conditions for protein expression were optimised to yield the maximum amount of protein or the best detection results using specific monoclonal antibodies or a scaffold binder against the expressed targets. The optimised DAPA system was able to increase by threefold the expression of a representative model protein while conserving recognition by a specific antibody. The amount of expressed protein in DAPA was comparable to those of classically spotted protein arrays. Reaction conditions can be tailored to suit the application of interest. DAPA represents a cost effective, easy and convenient way of producing protein arrays on demand. The reported work is expected to facilitate the application of DAPA for personalized medicine and screening purposes. Copyright © 2013 Elsevier B.V. All rights reserved.

Improved Performance Characteristics For Indium Antimonide Photovoltaic Detector Arrays Using A FET-Switched Multiplexing Technique

NASA Astrophysics Data System (ADS)

Ma, Yung-Lung; Ma, Chialo

1987-03-01

In this paper An Acoustic Imaging Recognition System (AIRS) will be introduced which is installed on an Intelligent Robotic System and can recognize different type of Hand tools' by Dynamic pattern recognition. The dynamic pattern recognition is approached by look up table method in this case, the method can save a lot of calculation time and it is practicable. The Acoustic Imaging Recognition System (AIRS) is consist of four parts _ position control unit, pulse-echo signal processing unit, pattern recognition unit and main control unit. The position control of AIRS can rotate an angle of ±5 degree Horizental and Vertical seperately, the purpose of rotation is to find the maximum reflection intensity area, from the distance, angles and intensity of the target we can decide the characteristic of this target, of course all the decision is target, of course all the decision is processed by the main control unit. In Pulse-Echo Signal Process Unit, we utilize the correlation method, to overcome the limitation of short burst of ultrasonic, because the Correlation system can transmit large time bandwidth signals and obtain their resolution and increased intensity through pulse compression in the correlation receiver. The output of correlator is sampled and transfer into digital data by p law coding method, and this data together with delay time T, angle information eH, eV will be sent into main control unit for further analysis. The recognition process in this paper, we use dynamic look up table method, in this method at first we shall set up serval recognition pattern table and then the new pattern scanned by Transducer array will be devided into serval stages and compare with the sampling table. The comparison is implemented by dynamic programing and Markovian process. All the hardware control signals, such as optimum delay time for correlator receiver, horizental and vertical rotation angle for transducer plate, are controlled by the Main Control Unit, the Main Control Unit also handles the pattern recognition process. The distance from the target to the transducer plate is limitted by the power and beam angle of transducer elements, in this AIRS Models, we use a narrow beam transducer and it's input voltage is 50V p-p. A Robot equipped with AIRS can not only measure the distance from the target but also recognize a three dimensional image of target from the image lab of Robot memory. Indexitems, Accoustic System, Supersonic transducer, Dynamic programming, Look-up-table, Image process, pattern Recognition, Quad Tree, Quadappoach.

Recognition and Localization of Speech by Adult Cochlear Implant Recipients Wearing a Digital Hearing Aid in the Nonimplanted Ear (Bimodal Hearing)

PubMed Central

Potts, Lisa G.; Skinner, Margaret W.; Litovsky, Ruth A.; Strube, Michael J; Kuk, Francis

2010-01-01

Background The use of bilateral amplification is now common clinical practice for hearing aid users but not for cochlear implant recipients. In the past, most cochlear implant recipients were implanted in one ear and wore only a monaural cochlear implant processor. There has been recent interest in benefits arising from bilateral stimulation that may be present for cochlear implant recipients. One option for bilateral stimulation is the use of a cochlear implant in one ear and a hearing aid in the opposite nonimplanted ear (bimodal hearing). Purpose This study evaluated the effect of wearing a cochlear implant in one ear and a digital hearing aid in the opposite ear on speech recognition and localization. Research Design A repeated-measures correlational study was completed. Study Sample Nineteen adult Cochlear Nucleus 24 implant recipients participated in the study. Intervention The participants were fit with a Widex Senso Vita 38 hearing aid to achieve maximum audibility and comfort within their dynamic range. Data Collection and Analysis Soundfield thresholds, loudness growth, speech recognition, localization, and subjective questionnaires were obtained six–eight weeks after the hearing aid fitting. Testing was completed in three conditions: hearing aid only, cochlear implant only, and cochlear implant and hearing aid (bimodal). All tests were repeated four weeks after the first test session. Repeated-measures analysis of variance was used to analyze the data. Significant effects were further examined using pairwise comparison of means or in the case of continuous moderators, regression analyses. The speech-recognition and localization tasks were unique, in that a speech stimulus presented from a variety of roaming azimuths (140 degree loudspeaker array) was used. Results Performance in the bimodal condition was significantly better for speech recognition and localization compared to the cochlear implant–only and hearing aid–only conditions. Performance was also different between these conditions when the location (i.e., side of the loudspeaker array that presented the word) was analyzed. In the bimodal condition, the speech-recognition and localization tasks were equal regardless of which side of the loudspeaker array presented the word, while performance was significantly poorer for the monaural conditions (hearing aid only and cochlear implant only) when the words were presented on the side with no stimulation. Binaural loudness summation of 1–3 dB was seen in soundfield thresholds and loudness growth in the bimodal condition. Measures of the audibility of sound with the hearing aid, including unaided thresholds, soundfield thresholds, and the Speech Intelligibility Index, were significant moderators of speech recognition and localization. Based on the questionnaire responses, participants showed a strong preference for bimodal stimulation. Conclusions These findings suggest that a well-fit digital hearing aid worn in conjunction with a cochlear implant is beneficial to speech recognition and localization. The dynamic test procedures used in this study illustrate the importance of bilateral hearing for locating, identifying, and switching attention between multiple speakers. It is recommended that unilateral cochlear implant recipients, with measurable unaided hearing thresholds, be fit with a hearing aid. PMID:19594084

Neural network-based system for pattern recognition through a fiber optic bundle

NASA Astrophysics Data System (ADS)

Gamo-Aranda, Javier; Rodriguez-Horche, Paloma; Merchan-Palacios, Miguel; Rosales-Herrera, Pablo; Rodriguez, M.

2001-04-01

A neural network based system to identify images transmitted through a Coherent Fiber-optic Bundle (CFB) is presented. Patterns are generated in a computer, displayed on a Spatial Light Modulator, imaged onto the input face of the CFB, and recovered optically by a CCD sensor array for further processing. Input and output optical subsystems were designed and used to that end. The recognition step of the transmitted patterns is made by a powerful, widely-used, neural network simulator running on the control PC. A complete PC-based interface was developed to control the different tasks involved in the system. An optical analysis of the system capabilities was carried out prior to performing the recognition step. Several neural network topologies were tested, and the corresponding numerical results are also presented and discussed.

Memory and event-related potentials for rapidly presented emotional pictures.

PubMed

Versace, Francesco; Bradley, Margaret M; Lang, Peter J

2010-08-01

Dense array event-related potentials (ERPs) and memory performance were assessed following rapid serial visual presentation (RSVP) of emotional and neutral pictures. Despite the extremely brief presentation, emotionally arousing pictures prompted an enhanced negative voltage over occipital sensors, compared to neutral pictures, replicating previous encoding effects. Emotionally arousing pictures were also remembered better in a subsequent recognition test, with higher hit rates and better discrimination performance. ERPs measured during the recognition test showed both an early (250-350 ms) frontally distributed difference between hits and correct rejections, and a later (400-500 ms), more centrally distributed difference, consistent with effects of recognition on ERPs typically found using slower presentation rates. The data are consistent with the hypothesis that features of affective pictures pop out during rapid serial visual presentation, prompting better memory performance.

Factors Affecting Outcomes in Cochlear Implant Recipients Implanted With a Perimodiolar Electrode Array Located in Scala Tympani.

PubMed

Holden, Laura K; Firszt, Jill B; Reeder, Ruth M; Uchanski, Rosalie M; Dwyer, Noël Y; Holden, Timothy A

2016-12-01

To identify primary biographic and audiologic factors contributing to cochlear implant (CI) performance variability in quiet and noise by controlling electrode array type and electrode position within the cochlea. Although CI outcomes have improved over time, considerable outcome variability still exists. Biographic, audiologic, and device-related factors have been shown to influence performance. Examining CI recipients with consistent array type and electrode position may allow focused investigation into outcome variability resulting from biographic and audiologic factors. Thirty-nine adults (40 ears) implanted for at least 6 months with a perimodiolar electrode array known (via computed tomography [CT] imaging) to be in scala tympani participated. Test materials, administered CI only, included monosyllabic words, sentences in quiet and noise, and spectral ripple discrimination. In quiet, scores were high with mean word and sentence scores of 76 and 87%, respectively; however, sentence scores decreased by an average of 35 percentage points when noise was added. A principal components (PC) analysis of biographic and audiologic factors found three distinct factors, PC1 Age, PC2 Duration, and PC3 Pre-op Hearing. PC1 Age was the only factor that correlated, albeit modestly, with speech recognition in quiet and noise. Spectral ripple discrimination strongly correlated with speech measures. For these recipients with consistent electrode position, PC1 Age was related to speech recognition performance. Consistent electrode position may have contributed to high speech understanding in quiet. Inter-subject variability in noise may have been influenced by auditory/cognitive processing, known to decline with age, and mechanisms that underlie spectral resolution ability.

The effect of sleep on item recognition and source memory recollection among shift-workers and permanent day-workers.

PubMed

Mawdsley, Matthew; Grasby, Katrina; Talk, Andrew

2014-10-01

We studied the effect of sleep versus wakefulness on item recognition and source memory recollection in a sample of shift-workers and permanent day-workers. Recognition of words that were previously viewed arrayed in quadrants of a page, and recollection of the original source location of the words on the page were assessed after a 12-h retention interval that was filled with wakefulness incorporating the subjects' work-shift, or an equal period that included sleep. Both shift-workers and permanent day-workers had poorer item recognition and source memory recollection when the retention interval was spent awake rather than including sleep. Shift-workers expressed larger deficits in performance than day-workers after wakefulness. This effect was not mediated by whether the shift-workers were on a day- or night-shift at the time of the study. These results indicate that sleep is an important contributor to successful item recognition and source recollection, and that mnemonic processing in shift-workers may be especially sensitive across their work-shift. © 2014 European Sleep Research Society.

An Indexed Combinatorial Library: The Synthesis and Testing of Insect Repellents

NASA Astrophysics Data System (ADS)

Miles, William H.; Gelato, Kathy A.; Pompizzi, Kristen M.; Scarbinsky, Aislinn M.; Albrecht, Brian K.; Reynolds, Elaine R.

2001-04-01

An indexed combinatorial library of amides was prepared by the reaction of amines and acid chlorides. A simple test for insect repellency using fruit flies (Drosophila melanogaster) allowed the determination of the most repellent sublibraries. The student-generated data were collected and analyzed to determine the most active amide(s) in the library. This experiment illustrates the fundamentals of combinatorial chemistry, a field that has undergone explosive growth in the last decade.

Fully parallel write/read in resistive synaptic array for accelerating on-chip learning

NASA Astrophysics Data System (ADS)

Gao, Ligang; Wang, I.-Ting; Chen, Pai-Yu; Vrudhula, Sarma; Seo, Jae-sun; Cao, Yu; Hou, Tuo-Hung; Yu, Shimeng

2015-11-01

A neuro-inspired computing paradigm beyond the von Neumann architecture is emerging and it generally takes advantage of massive parallelism and is aimed at complex tasks that involve intelligence and learning. The cross-point array architecture with synaptic devices has been proposed for on-chip implementation of the weighted sum and weight update in the learning algorithms. In this work, forming-free, silicon-process-compatible Ta/TaO x /TiO2/Ti synaptic devices are fabricated, in which >200 levels of conductance states could be continuously tuned by identical programming pulses. In order to demonstrate the advantages of parallelism of the cross-point array architecture, a novel fully parallel write scheme is designed and experimentally demonstrated in a small-scale crossbar array to accelerate the weight update in the training process, at a speed that is independent of the array size. Compared to the conventional row-by-row write scheme, it achieves >30× speed-up and >30× improvement in energy efficiency as projected in a large-scale array. If realistic synaptic device characteristics such as device variations are taken into an array-level simulation, the proposed array architecture is able to achieve ∼95% recognition accuracy of MNIST handwritten digits, which is close to the accuracy achieved by software using the ideal sparse coding algorithm.

Effector Mimics and Integrated Decoys, the Never-Ending Arms Race between Rice and Xanthomonas oryzae

PubMed Central

Zuluaga, Paola; Szurek, Boris; Koebnik, Ralf; Kroj, Thomas; Morel, Jean-Benoit

2017-01-01

Plants are constantly challenged by a wide range of pathogens and have therefore evolved an array of mechanisms to defend against them. In response to these defense systems, pathogens have evolved strategies to avoid recognition and suppress plant defenses (Brown and Tellier, 2011). Three recent reports dealing with the resistance of rice to Xanthomonas oryzae have added a new twist to our understanding of this fascinating co-evolutionary arms race (Ji et al., 2016; Read et al., 2016; Triplett et al., 2016). They show that pathogens also develop sophisticated effector mimics to trick recognition. PMID:28400786

Effector Mimics and Integrated Decoys, the Never-Ending Arms Race between Rice and Xanthomonas oryzae.

PubMed

Zuluaga, Paola; Szurek, Boris; Koebnik, Ralf; Kroj, Thomas; Morel, Jean-Benoit

2017-01-01

Plants are constantly challenged by a wide range of pathogens and have therefore evolved an array of mechanisms to defend against them. In response to these defense systems, pathogens have evolved strategies to avoid recognition and suppress plant defenses (Brown and Tellier, 2011). Three recent reports dealing with the resistance of rice to Xanthomonas oryzae have added a new twist to our understanding of this fascinating co-evolutionary arms race (Ji et al., 2016; Read et al., 2016; Triplett et al., 2016). They show that pathogens also develop sophisticated effector mimics to trick recognition.

False Recognition in DRM Lists with Low Association: A Normative Study

ERIC Educational Resources Information Center

Cadavid, Sara; Beato, María Soledad

2017-01-01

A wide array of studies have explored memory distortions with the Deese/Roediger-McDermott (DRM) paradigm, where participants study lists of words (e.g., "door," "glass," "pane," "shade," "ledge," etc.) that are associated to another nonpresented critical word (e.g., WINDOW). On a subsequent memory…

Development of Perceptual Expertise in Emotion Recognition

ERIC Educational Resources Information Center

Pollak, Seth D.; Messner, Michael; Kistler, Doris J.; Cohn, Jeffrey F.

2009-01-01

How do children's early social experiences influence their perception of emotion-specific information communicated by the face? To examine this question, we tested a group of abused children who had been exposed to extremely high levels of parental anger expression and physical threat. Children were presented with arrays of stimuli that depicted…

Sparse aperture 3D passive image sensing and recognition

NASA Astrophysics Data System (ADS)

Daneshpanah, Mehdi

The way we perceive, capture, store, communicate and visualize the world has greatly changed in the past century Novel three dimensional (3D) imaging and display systems are being pursued both in academic and industrial settings. In many cases, these systems have revolutionized traditional approaches and/or enabled new technologies in other disciplines including medical imaging and diagnostics, industrial metrology, entertainment, robotics as well as defense and security. In this dissertation, we focus on novel aspects of sparse aperture multi-view imaging systems and their application in quantum-limited object recognition in two separate parts. In the first part, two concepts are proposed. First a solution is presented that involves a generalized framework for 3D imaging using randomly distributed sparse apertures. Second, a method is suggested to extract the profile of objects in the scene through statistical properties of the reconstructed light field. In both cases, experimental results are presented that demonstrate the feasibility of the techniques. In the second part, the application of 3D imaging systems in sensing and recognition of objects is addressed. In particular, we focus on the scenario in which only 10s of photons reach the sensor from the object of interest, as opposed to hundreds of billions of photons in normal imaging conditions. At this level, the quantum limited behavior of light will dominate and traditional object recognition practices may fail. We suggest a likelihood based object recognition framework that incorporates the physics of sensing at quantum-limited conditions. Sensor dark noise has been modeled and taken into account. This framework is applied to 3D sensing of thermal objects using visible spectrum detectors. Thermal objects as cold as 250K are shown to provide enough signature photons to be sensed and recognized within background and dark noise with mature, visible band, image forming optics and detector arrays. The results suggest that one might not need to venture into exotic and expensive detector arrays and associated optics for sensing room-temperature thermal objects in complete darkness.

Combinatorial Dyson-Schwinger equations and inductive data types

NASA Astrophysics Data System (ADS)

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.

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

PubMed

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.

Combinatorial stresses kill pathogenic Candida species

PubMed Central

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

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

PubMed

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.

Polar exponential sensor arrays unify iconic and Hough space representation

NASA Technical Reports Server (NTRS)

Weiman, Carl F. R.

1990-01-01

The log-polar coordinate system, inherent in both polar exponential sensor arrays and log-polar remapped video imagery, is identical to the coordinate system of its corresponding Hough transform parameter space. The resulting unification of iconic and Hough domains simplifies computation for line recognition and eliminates the slope quantization problems inherent in the classical Cartesian Hough transform. The geometric organization of the algorithm is more amenable to massively parallel architectures than that of the Cartesian version. The neural architecture of the human visual cortex meets the geometric requirements to execute 'in-place' log-Hough algorithms of the kind described here.

A Universal Protocol for Photochemical Covalent Immobilization of Intact Carbohydrates for the Preparation of Carbohydrate Microarrays

PubMed Central

Wang, Huibin; Zhang, Yiming; Yuan, Xun; Chen, Yi; Yan, Mingdi

2010-01-01

A universal photochemical method has been established for the immobilization of intact carbohydrates and their analogues, and for the fabrication of carbohydrate microarrays. The method features the use of perfluorophenyl azide (PFPA)-modified substrates and the photochemical reaction of surface azido groups with printed carbohydrates. Various aldoses, ketoses, non-reducing sugars such as alditols and their derivatives can be directly arrayed on the PFPA-modified chips. The lectin-recognition ability of arrayed mannose, glucose and their oligo- and polysaccharides were confirmed using surface plasmon resonance imaging and laser-induced fluorescence imaging. PMID:21138274

General Linker Diversification Approach to Bivalent Ligand Assembly: Generation of an Array of Ligands for the Cation-Independent Mannose 6-Phosphate Receptor.

PubMed

Fei, Xiang; Zavorka, Megan E; Malik, Guillaume; Connelly, Christopher M; MacDonald, Richard G; Berkowitz, David B

2017-08-18

A generalized strategy is presented for the rapid assembly of a set of bivalent ligands with a variety of linking functionalities from a common monomer. Herein, an array of phosphatase-inert mannose-6-phosphonate-presenting ligands for the cation-independent-mannose 6-phosphate receptor (CI-MPR) is constructed. Receptor binding affinity varies with linking functionality-the simple amide and 1,5-triazole(tetrazole) being preferred over the 1,4-triazole. This approach is expected to find application across chemical biology, particularly in glycoscience, wherein multivalency often governs molecular recognition.

Neuron array with plastic synapses and programmable dendrites.

PubMed

Ramakrishnan, Shubha; Wunderlich, Richard; Hasler, Jennifer; George, Suma

2013-10-01

We describe a novel neuromorphic chip architecture that models neurons for efficient computation. Traditional architectures of neuron array chips consist of large scale systems that are interfaced with AER for implementing intra- or inter-chip connectivity. We present a chip that uses AER for inter-chip communication but uses fast, reconfigurable FPGA-style routing with local memory for intra-chip connectivity. We model neurons with biologically realistic channel models, synapses and dendrites. This chip is suitable for small-scale network simulations and can also be used for sequence detection, utilizing directional selectivity properties of dendrites, ultimately for use in word recognition.

A universal protocol for photochemical covalent immobilization of intact carbohydrates for the preparation of carbohydrate microarrays.

PubMed

Wang, Huibin; Zhang, Yiming; Yuan, Xun; Chen, Yi; Yan, Mingdi

2011-01-19

A universal photochemical method has been established for the immobilization of intact carbohydrates and their analogues, and for the fabrication of carbohydrate microarrays. The method features the use of perfluorophenyl azide (PFPA)-modified substrates and the photochemical reaction of surface azido groups with printed carbohydrates. Various aldoses, ketoses, nonreducing sugars such as alditols, and their derivatives can be directly arrayed on the PFPA-modified chips. The lectin-recognition ability of arrayed mannose, glucose, and their oligo- and polysaccharides were confirmed using surface plasmon resonance imaging and laser-induced fluorescence imaging.

Double-Barrier Memristive Devices for Unsupervised Learning and Pattern Recognition.

PubMed

Hansen, Mirko; Zahari, Finn; Ziegler, Martin; Kohlstedt, Hermann

2017-01-01

The use of interface-based resistive switching devices for neuromorphic computing is investigated. In a combined experimental and numerical study, the important device parameters and their impact on a neuromorphic pattern recognition system are studied. The memristive cells consist of a layer sequence Al/Al 2 O 3 /Nb x O y /Au and are fabricated on a 4-inch wafer. The key functional ingredients of the devices are a 1.3 nm thick Al 2 O 3 tunnel barrier and a 2.5 mm thick Nb x O y memristive layer. Voltage pulse measurements are used to study the electrical conditions for the emulation of synaptic functionality of single cells for later use in a recognition system. The results are evaluated and modeled in the framework of the plasticity model of Ziegler et al. Based on this model, which is matched to experimental data from 84 individual devices, the network performance with regard to yield, reliability, and variability is investigated numerically. As the network model, a computing scheme for pattern recognition and unsupervised learning based on the work of Querlioz et al. (2011), Sheridan et al. (2014), Zahari et al. (2015) is employed. This is a two-layer feedforward network with a crossbar array of memristive devices, leaky integrate-and-fire output neurons including a winner-takes-all strategy, and a stochastic coding scheme for the input pattern. As input pattern, the full data set of digits from the MNIST database is used. The numerical investigation indicates that the experimentally obtained yield, reliability, and variability of the memristive cells are suitable for such a network. Furthermore, evidence is presented that their strong I - V non-linearity might avoid the need for selector devices in crossbar array structures.

Evaluation of the Current Status of the Combinatorial Approach for the Study of Phase Diagrams

PubMed Central

Wong-Ng, W.

2012-01-01

This paper provides an evaluation of the effectiveness of using the high throughput combinatorial approach for preparing phase diagrams of thin film and bulk materials. Our evaluation is based primarily on examples of combinatorial phase diagrams that have been reported in the literature as well as based on our own laboratory experiments. Various factors that affect the construction of these phase diagrams are examined. Instrumentation and analytical approaches needed to improve data acquisition and data analysis are summarized. PMID:26900530

Research on thermal protection mechanism of forward-facing cavity and opposing jet combinatorial thermal protection system

NASA Astrophysics Data System (ADS)

Lu, Hai-Bo; Liu, Wei-Qiang

2014-04-01

Validated by the correlated experiments, a nose-tip with forward-facing cavity/opposing jet/the combinatorial configuration of forward-facing cavity and opposing jet thermal protection system (TPS) are investigated numerically. The physical mechanism of these TPS is discussed, and the cooling efficiency of them is compared. The combinatorial system is more suitable to be the TPS for the high speed vehicles which need fly under various flow conditions with long-range and long time.

Combinatorial approach to the representation of the Schur-Weyl duality in one-dimensional spin systems

NASA Astrophysics Data System (ADS)

Jakubczyk, Dorota; Jakubczyk, Paweł

2018-02-01

We propose combinatorial approach to the representation of Schur-Weyl duality in physical systems on the example of one-dimensional spin chains. Exploiting the Robinson-Schensted-Knuth algorithm, we perform decomposition of the dual group representations into irreducible representations in a fully combinatorial way. As representation space, we choose the Hilbert space of the spin chains, but this approach can be easily generalized to an arbitrary physical system where the Schur-Weyl duality works.

Massively multiplex single-cell Hi-C

PubMed Central

Ramani, Vijay; Deng, Xinxian; Qiu, Ruolan; Gunderson, Kevin L; Steemers, Frank J; Disteche, Christine M; Noble, William S; Duan, Zhijun; Shendure, Jay

2016-01-01

We present single-cell combinatorial indexed Hi-C (sciHi-C), which applies the concept of combinatorial cellular indexing to chromosome conformation capture. In this proof-of-concept, we generate and sequence six sciHi-C libraries comprising a total of 10,696 single cells. We use sciHi-C data to separate cells by karytoypic and cell-cycle state differences and identify cell-to-cell heterogeneity in mammalian chromosomal conformation. Our results demonstrate that combinatorial indexing is a generalizable strategy for single-cell genomics. PMID:28135255

Combinatorial Interdependence in Lottery

ERIC Educational Resources Information Center

Helman, Danny

2005-01-01

This paper examines a real life question of gamble facing lottery players. Combinatorial dependence plays a central role in shaping the game probabilistic structure, but might not carry the merited weight in punters' considerations.

Advances in OLED/OPD-based sensors and spectrometer-on-a-chip (Conference Presentation)

NASA Astrophysics Data System (ADS)

Shinar, Joseph; Kaudal, Rajiv; Manna, Eeshita; Fungura, Fadzai; Shinar, Ruth

2016-09-01

We describe ongoing advances toward achieving all-organic optical sensors and a spectrometer on a chip. Two-dimensional combinatorial arrays of microcavity OLEDs (μcOLEDs) with systematically varying optical cavity lengths are fabricated on a single chip by changing the thickness of different organic and/or spacer layers sandwiched between two metal electrodes (one very thin) that form the cavity. The broad spectral range is achieved by utilizing materials that result in white OLEDs (WOLEDs) when fabricated on a standard ITO substrate. The tunable and narrower emissions from the μcOLEDs serve as excitation sources in luminescent sensors and in monitoring light absorption. For each wavelength, the light from the μcOLED is partially absorbed by a sample under study and the light emitted by an electronically excited sample, or the transmitted light is detected by a photodetector (PD). To obtain a compact monitor, an organic PD (OPD) or a perovskite-based PD is integrated with the μcOLED array. We show the potential of encompassing a broader wavelength range by using WOLED materials to fabricate the μcOLEDs. The utility of the all-organic analytical devices is demonstrated by monitoring oxygen, and bioanalytes based on oxygen detection, as well as the absorption spectra of dyes.

Combined micro-Raman/UV-visible/fluorescence spectrometer for high-throughput analysis of microsamples.

PubMed

Noh, Jermim; Suh, Yung Doug; Park, Yong Ki; Jin, Seung Min; Kim, Soo Ho; Woo, Seong Ihl

2007-07-01

Combined micro-Raman/UV-visible (vis)/fluorescence spectroscopy system, which can evaluate an integrated array of more than 10,000 microsamples with a minimuma size of 5 microm within a few hours, has been developed for the first time. The array of microsamples is positioned on a computer-controlled XY translation microstage with a spatial resolution of 1 mum so that the spectra can be mapped with micron precision. Micro-Raman spectrometers have a high spectral resolution of about 2 cm(-1) over the wave number range of 150-3900 cm(-1), while UV-vis and fluorescence spectrometers have high spectral resolutions of 0.4 and 0.1 nm over the wavelength range of 190-900 nm, respectively. In particular, the signal-to-noise ratio of the micro-Raman spectroscopy has been improved by using a holographic Raman grating and a liquid-nitrogen-cooled charge-coupled device detector. The performance of the combined spectroscopy system has been demonstrated by the high-throughput screening of a combinatorial ferroelectric (i.e., BaTi(x)Zr(1-x)O(3)) library. This system makes possible the structure analysis of various materials including ferroelectrics, catalysts, phosphors, polymers, alloys, and so on for the development of novel materials and the ultrasensitive detection of trace amounts of pharmaceuticals and diagnostic agents.

Performance of Optimized Actuator and Sensor Arrays in an Active Noise Control System

NASA Technical Reports Server (NTRS)

Palumbo, D. L.; Padula, S. L.; Lyle, K. H.; Cline, J. H.; Cabell, R. H.

1996-01-01

Experiments have been conducted in NASA Langley's Acoustics and Dynamics Laboratory to determine the effectiveness of optimized actuator/sensor architectures and controller algorithms for active control of harmonic interior noise. Tests were conducted in a large scale fuselage model - a composite cylinder which simulates a commuter class aircraft fuselage with three sections of trim panel and a floor. Using an optimization technique based on the component transfer functions, combinations of 4 out of 8 piezoceramic actuators and 8 out of 462 microphone locations were evaluated against predicted performance. A combinatorial optimization technique called tabu search was employed to select the optimum transducer arrays. Three test frequencies represent the cases of a strong acoustic and strong structural response, a weak acoustic and strong structural response and a strong acoustic and weak structural response. Noise reduction was obtained using a Time Averaged/Gradient Descent (TAGD) controller. Results indicate that the optimization technique successfully predicted best and worst case performance. An enhancement of the TAGD control algorithm was also evaluated. The principal components of the actuator/sensor transfer functions were used in the PC-TAGD controller. The principal components are shown to be independent of each other while providing control as effective as the standard TAGD.

Distant Speech Recognition Using a Microphone Array Network

NASA Astrophysics Data System (ADS)

Nakano, Alberto Yoshihiro; Nakagawa, Seiichi; Yamamoto, Kazumasa

In this work, spatial information consisting of the position and orientation angle of an acoustic source is estimated by an artificial neural network (ANN). The estimated position of a speaker in an enclosed space is used to refine the estimated time delays for a delay-and-sum beamformer, thus enhancing the output signal. On the other hand, the orientation angle is used to restrict the lexicon used in the recognition phase, assuming that the speaker faces a particular direction while speaking. To compensate the effect of the transmission channel inside a short frame analysis window, a new cepstral mean normalization (CMN) method based on a Gaussian mixture model (GMM) is investigated and shows better performance than the conventional CMN for short utterances. The performance of the proposed method is evaluated through Japanese digit/command recognition experiments.

Pattern recognition of electronic bit-sequences using a semiconductor mode-locked laser and spatial light modulators

NASA Astrophysics Data System (ADS)

Bhooplapur, Sharad; Akbulut, Mehmetkan; Quinlan, Franklyn; Delfyett, Peter J.

2010-04-01

A novel scheme for recognition of electronic bit-sequences is demonstrated. Two electronic bit-sequences that are to be compared are each mapped to a unique code from a set of Walsh-Hadamard codes. The codes are then encoded in parallel on the spectral phase of the frequency comb lines from a frequency-stabilized mode-locked semiconductor laser. Phase encoding is achieved by using two independent spatial light modulators based on liquid crystal arrays. Encoded pulses are compared using interferometric pulse detection and differential balanced photodetection. Orthogonal codes eight bits long are compared, and matched codes are successfully distinguished from mismatched codes with very low error rates, of around 10-18. This technique has potential for high-speed, high accuracy recognition of bit-sequences, with applications in keyword searches and internet protocol packet routing.

A microfabricated platform with hydrogel arrays for 3D mechanical stimulation of cells.

PubMed

Liu, Haijiao; Usprech, Jenna; Sun, Yu; Simmons, Craig A

2016-04-01

Cellular microenvironments present cells with multiple stimuli, including not only soluble biochemical and insoluble matrix cues but also mechanical factors. Biomaterial array platforms have been used to combinatorially and efficiently probe and define two-dimensional (2D) and 3D microenvironmental cues to guide cell functions for tissue engineering applications. However, there are few examples of array platforms that include dynamic mechanical forces, particularly to enable stretching of 3D cell-seeded biomaterials, which is relevant to engineering connective and cardiovascular tissues. Here we present a deformable membrane platform that enables 3D dynamic mechanical stretch of arrayed biomaterial constructs. Cell-seeded polyethylene glycol norbornene (PEG-NB) hydrogels were bound to miniaturized deformable membranes via a thiol-ene reaction with off-stoichiometry thiol-ene based polydimethylsiloxane (OSTE-PDMS) as the membrane material. Bonding to OSTE-PDMS enabled the 3D hydrogel microconstructs to be cyclically deformed and stretched by the membrane. As a first demonstration, human mesenchymal stromal cells (MSCs) embedded in PEG-NB were stretched for several days. They were found to be viable, spread in the 3D hydrogels, and exhibited a contractile myofibroblast phenotype when exposed to dynamic 3D mechanical deformation. This platform, which is readily scalable to larger arrays, enables systematic interrogation of the relationships between combinations of 3D mechanobiological cues and cellular responses, and thus has the potential to identify strategies to predictably control the construction of functional engineered tissues. Current high-throughput biomaterial screening approaches fail to consider the effects of dynamic mechanical stimulation, despite its importance in a wide variety of regenerative medicine applications. To meet this need, we developed a deformable membrane platform that enables 3D dynamic stretch of arrayed biomaterial constructs. Our approach combines microtechnologies fabricated with off-stoichiometry thiol-ene based polydimethylsiloxane membranes that can covalently bond cell-seeded polyethylene glycol norbornene 3D hydrogels, a model biomaterial with tunable adhesive, elastic and degradation characteristics. As a first demonstration, we show that human mesenchymal stromal cells embedded in hydrogels and subjected to dynamic mechanical stimulation undergo myofibroblast differentiation. This system is readily scaled up to larger arrays, and will enable systematic and efficient screening of combinations of 3D mechanobiological and biomaterial cues on cell fate and function. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Micro-Electronic Nose System

NASA Astrophysics Data System (ADS)

Zee, Frank C.

2011-12-01

The ability to "smell" various gas vapors and complex odors is important for many applications such as environmental monitoring for detecting toxic gases as well as quality control in the processing of food, cosmetics, and other chemical products for commercial industries. Mimicking the architecture of the biological nose, a miniature electronic nose system was designed and developed consisting of an array of sensor devices, signal-processing circuits, and software pattern-recognition algorithms. The array of sensors used polymer/carbon-black composite thin-films, which would swell or expand reversibly and reproducibly and cause a resistance change upon exposure to a wide variety of gases. Two types of sensor devices were fabricated using silicon micromachining techniques to form "wells" that confined the polymer/carbon-black to a small and specific area. The first type of sensor device formed the "well" by etching into the silicon substrate using bulk micromachining. The second type built a high-aspect-ratio "well" on the surface of a silicon wafer using SU-8 photoresist. Two sizes of "wells" were fabricated: 500 x 600 mum² and 250 x 250 mum². Custom signal-processing circuits were implemented on a printed circuit board and as an application-specific integrated-circuit (ASIC) chip. The circuits were not only able to measure and amplify the small resistance changes, which corresponded to small ppm (parts-per-million) changes in gas concentrations, but were also adaptable to accommodate the various characteristics of the different thin-films. Since the thin-films were not specific to any one particular gas vapor, an array of sensors each containing a different thin-film was used to produce a distributed response pattern when exposed to a gas vapor. Pattern recognition, including a clustering algorithm and two artificial neural network algorithms, was used to classify the response pattern and identify the gas vapor or odor. Two gas experiments were performed, one at low gas concentrations between 100 and 600 ppm for two gas vapors and the other at high gas concentrations between 2000 ppm and the saturated vapor pressure of three gas vapors. The array of sensors and circuits were able to uniquely detect and measure these gas vapors and showed a linear response to their concentration levels for both experiments. The results also demonstrated that a reduction in the sensor area by two orders of magnitude (from 4.32 mm² to 0.0625 mm²) did not affect the sensor response. By applying pattern-recognition algorithms, the electronic nose system was able to correctly identify the different gas vapors from the pattern responses of the sensor array.

Development of conductometric biosensor array for simultaneous determination of maltose, lactose, sucrose and glucose.

PubMed

Soldatkin, O O; Peshkova, V M; Saiapina, O Y; Kucherenko, I S; Dudchenko, O Y; Melnyk, V G; Vasylenko, O D; Semenycheva, L M; Soldatkin, A P; Dzyadevych, S V

2013-10-15

The aim of this work was to develop an array of biosensors for simultaneous determination of four carbohydrates in solution. Several enzyme systems selective to lactose, maltose, sucrose and glucose were immobilised on the surface of four conductometric transducers and served as bio-recognition elements of the biosensor array. Direct enzyme analysis carried out by the developed biosensors was highly sensitive to the corresponding substrates. The analysis lasted 2 min. The dynamic range of substrate determination extended from 0.001 mM to 1.0-3.0mM, and strongly depended on the enzyme system used. An effect of the solution pH, ionic strength and buffer capacity on the biosensors responses was investigated; the conditions of simultaneous operation of all biosensors were optimised. The data on cross-impact of the substrates of all biosensors were obtained; the biosensor selectivity towards possible interfering carbohydrates was tested. The developed biosensor array showed good signal reproducibility and storage stability. The biosensor array is suited for simultaneous, quick, simple, and selective determination of maltose, lactose, sucrose and glucose. © 2013 Elsevier B.V. All rights reserved.

Higher Education: The Online Teaching and Learning Experience

ERIC Educational Resources Information Center

Barr, Betty A.; Miller, Sonya F.

2013-01-01

Globally, higher education, as well as K-12, utilizes online teaching to ensure that a wide array of learning opportunities are available for students in a highly competitive technological arena. The most significant influence in education in recent years is the increase and recognition of private for-profit adult distance and online education…

Self-Recognition of the Body and Its Parts during Late Adolescence.

ERIC Educational Resources Information Center

Collins, John K.

1981-01-01

Male and female student volunteers were photographed nude in three orientations and asked to identify bodily parts from an array of photographs grouped according to height and linearity. Results are discussed in terms of ego involvement, narcissism, and the increased attention given to the body during adolescence. (Author/GK)

A novel hanging spherical drop system for the generation of cellular spheroids and high throughput combinatorial drug screening.

PubMed

Neto, A I; Correia, C R; Oliveira, M B; Rial-Hermida, M I; Alvarez-Lorenzo, C; Reis, R L; Mano, J F

2015-04-01

We propose a novel hanging spherical drop system for anchoring arrays of droplets of cell suspension based on the use of biomimetic superhydrophobic flat substrates, with controlled positional adhesion and minimum contact with a solid substrate. By facing down the platform, it was possible to generate independent spheroid bodies in a high throughput manner, in order to mimic in vivo tumour models on the lab-on-chip scale. To validate this system for drug screening purposes, the toxicity of the anti-cancer drug doxorubicin in cell spheroids was tested and compared to cells in 2D culture. The advantages presented by this platform, such as feasibility of the system and the ability to control the size uniformity of the spheroid, emphasize its potential to be used as a new low cost toolbox for high-throughput drug screening and in cell or tissue engineering.

Biosynthesis of antimycins with a reconstituted 3-formamidosalicylate pharmacophore in Escherichia coli.

PubMed

Liu, Joyce; Zhu, Xuejun; Seipke, Ryan F; Zhang, Wenjun

2015-05-15

Antimycins are a family of natural products generated from a hybrid nonribosomal peptide synthetase (NRPS)-polyketide synthase (PKS) assembly line. Although they possess an array of useful biological activities, their structural complexity makes chemical synthesis challenging, and their biosynthesis has thus far been dependent on slow-growing source organisms. Here, we reconstituted the biosynthesis of antimycins in Escherichia coli, a versatile host that is robust and easy to manipulate genetically. Along with Streptomyces genetic studies, the heterologous expression of different combinations of ant genes enabled us to systematically confirm the functions of the modification enzymes, AntHIJKL and AntO, in the biosynthesis of the 3-formamidosalicylate pharmacophore of antimycins. Our E. coli-based antimycin production system can not only be used to engineer the increased production of these bioactive compounds, but it also paves the way for the facile generation of novel and diverse antimycin analogues through combinatorial biosynthesis.

Combinatorial electrochemical synthesis and screening of Pt-WO3 catalysts for electro-oxidation of methanol

NASA Astrophysics Data System (ADS)

Jayaraman, Shrisudersan; Baeck, Sung-Hyeon; Jaramillo, Thomas F.; Kleiman-Shwarsctein, Alan; McFarland, Eric W.

2005-06-01

An automated system for high-throughput electrochemical synthesis and screening of fuel cell electro-oxidation catalysts is described. This system consists of an electrode probe that contains counter and reference electrodes that can be positioned inside an array of electrochemical cells created within a polypropylene block. The electrode probe is attached to an automated of X-Y-Z motion system. An externally controlled potentiostat is used to apply the electrochemical potential to the catalyst substrate. The motion and electrochemical control are integrated using a user-friendly software interface. During automated synthesis the deposition potential and/or current may be controlled by a pulse program triggered by the software using a data acquisition board. The screening includes automated experiments to obtain cyclic voltammograms. As an example, a platinum-tungsten oxide (Pt-WO3) library was synthesized and characterized for reactivity towards methanol electro-oxidation.

Quantitative analysis of modified proteins and their positional isomers by tandem mass spectrometry: human histone H4.

PubMed

Pesavento, James J; Mizzen, Craig A; Kelleher, Neil L

2006-07-01

Here we show that fragment ion abundances from dissociation of ions created from mixtures of multiply modified histone H4 (11 kDa) or of N-terminal synthetic peptides (2 kDa) correspond to their respective intact ion abundances measured by Fourier transform mass spectrometry. Isomeric mixtures of modified forms of the same protein are resolved and quantitated with a precision of

Characterization and electrochemical response of DNA functionalized 2nm gold nanoparticles confined in a nanochannel array.

PubMed

Peinetti, Ana S; Ceretti, Helena; Mizrahi, Martín; González, Graciela A; Ramírez, Silvana A; Requejo, Félix G; Montserrat, Javier M; Battaglini, Fernando

2018-06-01

Polyvalent gold nanoparticle oligonucleotide conjugates are subject of intense research. Even though 2nm diameter AuNPs have been previously modified with DNA, little is known about their structure and electrochemical behavior. In this work, we examine the influence of different surface modification strategies on the interplay between the meso-organization and the molecular recognition properties of a 27-mer DNA strand. This DNA strand is functionalized with different sulfur-containing moieties and immobilized on 2nm gold nanoparticles confined on a nanoporous alumina, working the whole system as an electrode array. Surface coverages were determined by EXAFS and the performance as recognition elements for impedance-based sensors is evaluated. Our results prove that low DNA coverages on the confined nanoparticles prompt to a more sensitive response, showing the relevance in avoiding the DNA strand overcrowding. The system was able to determine a concentration as low as 100pM of the complementary strand, thus introducing the foundations for the construction of label-free genosensors at the nanometer scale. Copyright © 2018 Elsevier B.V. All rights reserved.

A Systematic Study of Simple Combinatorial Configurations.

ERIC Educational Resources Information Center

Dubois, Jean-Guy

1984-01-01

A classification of the simple combinatorial configurations which correspond to various cases of distribution and ordering of objects into boxes is given (in French). Concrete descriptions, structured relations, translations, and formalizations are discussed. (MNS)

Combinatorial Mathematics: Research into Practice

ERIC Educational Resources Information Center

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.

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

PubMed

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 vector fields and the valley structure of fitness landscapes.

PubMed

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.

Combinatorial chemical bath deposition of CdS contacts for chalcogenide photovoltaics

DOE PAGES

Mokurala, Krishnaiah; Baranowski, Lauryn L.; de Souza Lucas, Francisco W.; ...

2016-08-01

Contact layers play an important role in thin film solar cells, but new material development and optimization of its thickness is usually a long and tedious process. A high-throughput experimental approach has been used to accelerate the rate of research in photovoltaic (PV) light absorbers and transparent conductive electrodes, however the combinatorial research on contact layers is less common. Here, we report on the chemical bath deposition (CBD) of CdS thin films by combinatorial dip coating technique and apply these contact layers to Cu(In,Ga)Se 2 (CIGSe) and Cu 2ZnSnSe 4 (CZTSe) light absorbers in PV devices. Combinatorial thickness steps ofmore » CdS thin films were achieved by removal of the substrate from the chemical bath, at regular intervals of time, and in equal distance increments. The trends in the photoconversion efficiency and in the spectral response of the PV devices as a function of thickness of CdS contacts were explained with the help of optical and morphological characterization of the CdS thin films. The maximum PV efficiency achieved for the combinatorial dip-coating CBD was similar to that for the PV devices processed using conventional CBD. Finally, the results of this study lead to the conclusion that combinatorial dip-coating can be used to accelerate the optimization of PV device performance of CdS and other candidate contact layers for a wide range of emerging absorbers.« less

Polynomial functors and combinatorial Dyson-Schwinger equations

NASA Astrophysics Data System (ADS)

Kock, Joachim

2017-04-01

We present a general abstract framework for combinatorial Dyson-Schwinger equations, in which combinatorial identities are lifted to explicit bijections of sets, and more generally equivalences of groupoids. Key features of combinatorial Dyson-Schwinger equations are revealed to follow from general categorical constructions and universal properties. Rather than beginning with an equation inside a given Hopf algebra and referring to given Hochschild 1-cocycles, our starting point is an abstract fixpoint equation in groupoids, shown canonically to generate all the algebraic structures. Precisely, for any finitary polynomial endofunctor P defined over groupoids, the system of combinatorial Dyson-Schwinger equations X = 1 + P(X) has a universal solution, namely the groupoid of P-trees. The isoclasses of P-trees generate naturally a Connes-Kreimer-like bialgebra, in which the abstract Dyson-Schwinger equation can be internalised in terms of canonical B+-operators. The solution to this equation is a series (the Green function), which always enjoys a Faà di Bruno formula, and hence generates a sub-bialgebra isomorphic to the Faà di Bruno bialgebra. Varying P yields different bialgebras, and cartesian natural transformations between various P yield bialgebra homomorphisms and sub-bialgebras, corresponding for example to truncation of Dyson-Schwinger equations. Finally, all constructions can be pushed inside the classical Connes-Kreimer Hopf algebra of trees by the operation of taking core of P-trees. A byproduct of the theory is an interpretation of combinatorial Green functions as inductive data types in the sense of Martin-Löf type theory (expounded elsewhere).

Facile hyphenation of gas chromatography and a microcantilever array sensor for enhanced selectivity.

PubMed

Chapman, Peter J; Vogt, Frank; Dutta, Pampa; Datskos, Panos G; Devault, Gerald L; Sepaniak, Michael J

2007-01-01

The very simple coupling of a standard, packed-column gas chromatograph with a microcantilever array (MCA) is demonstrated for enhanced selectivity and potential analyte identification in the analysis of volatile organic compounds (VOCs). The cantilevers in MCAs are differentially coated on one side with responsive phases (RPs) and produce bending responses of the cantilevers due to analyte-induced surface stresses. Generally, individual components are difficult to elucidate when introduced to MCA systems as mixtures, although pattern recognition techniques are helpful in identifying single components, binary mixtures, or composite responses of distinct mixtures (e.g., fragrances). In the present work, simple test VOC mixtures composed of acetone, ethanol, and trichloroethylene (TCE) in pentane and methanol and acetonitrile in pentane are first separated using a standard gas chromatograph and then introduced into a MCA flow cell. Significant amounts of response diversity to the analytes in the mixtures are demonstrated across the RP-coated cantilevers of the array. Principal component analysis is used to demonstrate that only three components of a four-component VOC mixture could be identified without mixture separation. Calibration studies are performed, demonstrating a good linear response over 2 orders of magnitude for each component in the primary study mixture. Studies of operational parameters including column temperature, column flow rate, and array cell temperature are conducted. Reproducibility studies of VOC peak areas and peak heights are also carried out showing RSDs of less than 4 and 3%, respectively, for intra-assay studies. Of practical significance is the facile manner by which the hyphenation of a mature separation technique and the burgeoning sensing approach is accomplished, and the potential to use pattern recognition techniques with MCAs as a new type of detector for chromatography with analyte-identifying capabilities.

Zoledronic acid-encapsulating self-assembling nanoparticles and doxorubicin: a combinatorial approach to overcome simultaneously chemoresistance and immunoresistance in breast tumors

PubMed Central

Kopecka, Joanna; Porto, Stefania; Lusa, Sara; Gazzano, Elena; Salzano, Giuseppina; Pinzòn-Daza, Martha Leonor; Giordano, Antonio; Desiderio, Vincenzo; Ghigo, Dario; De Rosa, Giuseppe; Caraglia, Michele; Riganti, Chiara

2016-01-01

The resistance to chemotherapy and the tumor escape from host immunosurveillance are the main causes of the failure of anthracycline-based regimens in breast cancer, where an effective chemo-immunosensitizing strategy is lacking. The clinically used aminobisphosphonate zoledronic acid (ZA) reverses chemoresistance and immunoresistance in vitro. Previously we developed a nanoparticle-based zoledronic acid-containing formulation (NZ) that allowed a higher intratumor delivery of the drug compared with free ZA in vivo. We tested its efficacy in combination with doxorubicin in breast tumors refractory to chemotherapy and immune system recognition as a new combinatorial approach to produce chemo- and immunosensitization. NZ reduced the IC50 of doxorubicin in human and murine chemoresistant breast cancer cells and restored the doxorubicin efficacy against chemo-immunoresistant tumors implanted in immunocompetent mice. By reducing the metabolic flux through the mevalonate pathway, NZ lowered the activity of Ras/ERK1/2/HIF-1α axis and the expression of P-glycoprotein, decreased the glycolysis and the mitochondrial respiratory chain, induced a cytochrome c/caspase 9/caspase 3-dependent apoptosis, thus restoring the direct cytotoxic effects of doxorubicin on tumor cell. Moreover, NZ restored the doxorubicin-induced immunogenic cell death and reversed the tumor-induced immunosuppression due to the production of kynurenine, by inhibiting the STAT3/indoleamine 2,3 dioxygenase axis. These events increased the number of dendritic cells and decreased the number of immunosuppressive T-regulatory cells infiltrating the tumors. Our work proposes the use of nanoparticle encapsulating zoledronic acid as an effective tool overcoming at the same time chemoresistance and immunoresistance in breast tumors, thanks to the effects exerted on tumor cell and tumor-infiltrating immune cells. PMID:26980746

Polyketide intermediate mimics as probes for revealing cryptic stereochemistry of ketoreductase domains.

PubMed

Li, Yang; Fiers, William D; Bernard, Steffen M; Smith, Janet L; Aldrich, Courtney C; Fecik, Robert A

2014-12-19

Among natural product families, polyketides have shown the most promise for combinatorial biosynthesis of natural product-like libraries. Though recent research in the area has provided many mechanistic revelations, a basic-level understanding of kinetic and substrate tolerability is still needed before the full potential of combinatorial biosynthesis can be realized. We have developed a novel set of chemical probes for the study of ketoreductase domains of polyketide synthases. This chemical tool-based approach was validated using the ketoreductase of pikromycin module 2 (PikKR2) as a model system. Triketide substrate mimics 12 and 13 were designed to increase stability (incorporating a nonhydrolyzable thioether linkage) and minimize nonessential functionality (truncating the phosphopantetheinyl arm). PikKR2 reduction product identities as well as steady-state kinetic parameters were determined by a combination of LC-MS/MS analysis of synthetic standards and a NADPH consumption assay. The d-hydroxyl product is consistent with bioinformatic analysis and results from a complementary biochemical and molecular biological approach. When compared to widely employed substrates in previous studies, diketide 63 and trans-decalone 64, substrates 12 and 13 showed 2-10 fold lower K(M) values (2.4 ± 0.8 and 7.8 ± 2.7 mM, respectively), indicating molecular recognition of intermediate-like substrates. Due to an abundance of the nonreducable enol-tautomer, the k(cat) values were attenuated by as much as 15-336 fold relative to known substrates. This study reveals the high stereoselectivity of PikKR2 in the face of gross substrate permutation, highlighting the utility of a chemical probe-based approach in the study of polyketide ketoreductases.

Differential Recognition Preferences of the Three Src Homology 3 (SH3) Domains from the Adaptor CD2-associated Protein (CD2AP) and Direct Association with Ras and Rab Interactor 3 (RIN3)*

PubMed Central

Rouka, Evgenia; Simister, Philip C.; Janning, Melanie; Kumbrink, Joerg; Konstantinou, Tassos; Muniz, João R. C.; Joshi, Dhira; O'Reilly, Nicola; Volkmer, Rudolf; Ritter, Brigitte; Knapp, Stefan; von Delft, Frank; Kirsch, Kathrin H.; Feller, Stephan M.

2015-01-01

CD2AP is an adaptor protein involved in membrane trafficking, with essential roles in maintaining podocyte function within the kidney glomerulus. CD2AP contains three Src homology 3 (SH3) domains that mediate multiple protein-protein interactions. However, a detailed comparison of the molecular binding preferences of each SH3 remained unexplored, as well as the discovery of novel interactors. Thus, we studied the binding properties of each SH3 domain to the known interactor Casitas B-lineage lymphoma protein (c-CBL), conducted a peptide array screen based on the recognition motif PxPxPR and identified 40 known or novel candidate binding proteins, such as RIN3, a RAB5-activating guanine nucleotide exchange factor. CD2AP SH3 domains 1 and 2 generally bound with similar characteristics and specificities, whereas the SH3-3 domain bound more weakly to most peptide ligands tested yet recognized an unusually extended sequence in ALG-2-interacting protein X (ALIX). RIN3 peptide scanning arrays revealed two CD2AP binding sites, recognized by all three SH3 domains, but SH3-3 appeared non-functional in precipitation experiments. RIN3 recruited CD2AP to RAB5a-positive early endosomes via these interaction sites. Permutation arrays and isothermal titration calorimetry data showed that the preferred binding motif is Px(P/A)xPR. Two high-resolution crystal structures (1.65 and 1.11 Å) of CD2AP SH3-1 and SH3-2 solved in complex with RIN3 epitopes 1 and 2, respectively, indicated that another extended motif is relevant in epitope 2. In conclusion, we have discovered novel interaction candidates for CD2AP and characterized subtle yet significant differences in the recognition preferences of its three SH3 domains for c-CBL, ALIX, and RIN3. PMID:26296892

Combinatorial invariants and covariants as tools for conical intersections.

PubMed

Ryb, Itai; Baer, Roi

2004-12-01

The combinatorial invariant and covariant are introduced as practical tools for analysis of conical intersections in molecules. The combinatorial invariant is a quantity depending on adiabatic electronic states taken at discrete nuclear configuration points. It is invariant to the phase choice (gauge) of these states. In the limit that the points trace a loop in nuclear configuration space, the value of the invariant approaches the corresponding Berry phase factor. The Berry phase indicates the presence of an odd or even number of conical intersections on surfaces bounded by these loops. Based on the combinatorial invariant, we develop a computationally simple and efficient method for locating conical intersections. The method is robust due to its use of gauge invariant nature. It does not rely on the landscape of intersecting potential energy surfaces nor does it require the computation of nonadiabatic couplings. We generalize the concept to open paths and combinatorial covariants for higher dimensions obtaining a technique for the construction of the gauge-covariant adiabatic-diabatic transformation matrix. This too does not make use of nonadiabatic couplings. The importance of using gauge-covariant expressions is underlined throughout. These techniques can be readily implemented by standard quantum chemistry codes. (c) 2004 American Institute of Physics.

On the suitability of different representations of solid catalysts for combinatorial library design by genetic algorithms.

PubMed

Gobin, Oliver C; Schüth, Ferdi

2008-01-01

Genetic algorithms are widely used to solve and optimize combinatorial problems and are more often applied for library design in combinatorial chemistry. Because of their flexibility, however, their implementation can be challenging. In this study, the influence of the representation of solid catalysts on the performance of genetic algorithms was systematically investigated on the basis of a new, constrained, multiobjective, combinatorial test problem with properties common to problems in combinatorial materials science. Constraints were satisfied by penalty functions, repair algorithms, or special representations. The tests were performed using three state-of-the-art evolutionary multiobjective algorithms by performing 100 optimization runs for each algorithm and test case. Experimental data obtained during the optimization of a noble metal-free solid catalyst system active in the selective catalytic reduction of nitric oxide with propene was used to build up a predictive model to validate the results of the theoretical test problem. A significant influence of the representation on the optimization performance was observed. Binary encodings were found to be the preferred encoding in most of the cases, and depending on the experimental test unit, repair algorithms or penalty functions performed best.

Direct Profiling the Post-Translational Modification Codes of a Single Protein Immobilized on a Surface Using Cu-free Click Chemistry.

PubMed

Kim, Kyung Lock; Park, Kyeng Min; Murray, James; Kim, Kimoon; Ryu, Sung Ho

2018-05-23

Combinatorial post-translational modifications (PTMs), which can serve as dynamic "molecular barcodes", have been proposed to regulate distinct protein functions. However, studies of combinatorial PTMs on single protein molecules have been hindered by a lack of suitable analytical methods. Here, we describe erasable single-molecule blotting (eSiMBlot) for combinatorial PTM profiling. This assay is performed in a highly multiplexed manner and leverages the benefits of covalent protein immobilization, cyclic probing with different antibodies, and single molecule fluorescence imaging. Especially, facile and efficient covalent immobilization on a surface using Cu-free click chemistry permits multiple rounds (>10) of antibody erasing/reprobing without loss of antigenicity. Moreover, cumulative detection of coregistered multiple data sets for immobilized single-epitope molecules, such as HA peptide, can be used to increase the antibody detection rate. Finally, eSiMBlot enables direct visualization and quantitative profiling of combinatorial PTM codes at the single-molecule level, as we demonstrate by revealing the novel phospho-codes of ligand-induced epidermal growth factor receptor. Thus, eSiMBlot provides an unprecedentedly simple, rapid, and versatile platform for analyzing the vast number of combinatorial PTMs in biological pathways.

Direct Profiling the Post-Translational Modification Codes of a Single Protein Immobilized on a Surface Using Cu-free Click Chemistry

PubMed Central

2018-01-01

Combinatorial post-translational modifications (PTMs), which can serve as dynamic “molecular barcodes”, have been proposed to regulate distinct protein functions. However, studies of combinatorial PTMs on single protein molecules have been hindered by a lack of suitable analytical methods. Here, we describe erasable single-molecule blotting (eSiMBlot) for combinatorial PTM profiling. This assay is performed in a highly multiplexed manner and leverages the benefits of covalent protein immobilization, cyclic probing with different antibodies, and single molecule fluorescence imaging. Especially, facile and efficient covalent immobilization on a surface using Cu-free click chemistry permits multiple rounds (>10) of antibody erasing/reprobing without loss of antigenicity. Moreover, cumulative detection of coregistered multiple data sets for immobilized single-epitope molecules, such as HA peptide, can be used to increase the antibody detection rate. Finally, eSiMBlot enables direct visualization and quantitative profiling of combinatorial PTM codes at the single-molecule level, as we demonstrate by revealing the novel phospho-codes of ligand-induced epidermal growth factor receptor. Thus, eSiMBlot provides an unprecedentedly simple, rapid, and versatile platform for analyzing the vast number of combinatorial PTMs in biological pathways.

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

DOT National Transportation Integrated Search

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...

Postage stamp-sized array sensor for the sensitive screening test of heavy-metal ions.

PubMed

Zhang, Yu; Li, Xiao; Li, Hui; Song, Ming; Feng, Liang; Guan, Yafeng

2014-10-07

The sensitive determination of heavy-metal ions has been widely investigated in recent years due to their threat to the environment and to human health. Among various analytical detection techniques, inexpensive colorimetric testing papers/strips play a very important role. The limitation, however, is also clear: the sensitivity is usually low and the selectivity is poor. In this work, we have developed a postage stamp-sized array sensor composed of nine commercially available heterocyclic azo indicators. Combining filtration-based enrichment with an array of technologies-based pattern-recognition, we have obtained the discrimination capability for seven heavy-metal ions (Hg(2+), Pb(2+), Ag(+), Ni(2+), Cu(2+), Zn(2+), and Co(2+)) at their Chinese wastewater discharge standard concentrations. The allowable detection level of Hg(2+) was down to 0.05 mg L(-1). The heavy-metal ions screening test was readily achieved using a standard chemometric approach. And the array sensor applied well in real water samples.

Modeling the effect of channel number and interaction on consonant recognition in a cochlear implant peak-picking strategy.

PubMed

Verschuur, Carl

2009-03-01

Difficulties in speech recognition experienced by cochlear implant users may be attributed both to information loss caused by signal processing and to information loss associated with the interface between the electrode array and auditory nervous system, including cross-channel interaction. The objective of the work reported here was to attempt to partial out the relative contribution of these different factors to consonant recognition. This was achieved by comparing patterns of consonant feature recognition as a function of channel number and presence/absence of background noise in users of the Nucleus 24 device with normal hearing subjects listening to acoustic models that mimicked processing of that device. Additionally, in the acoustic model experiment, a simulation of cross-channel spread of excitation, or "channel interaction," was varied. Results showed that acoustic model experiments were highly correlated with patterns of performance in better-performing cochlear implant users. Deficits to consonant recognition in this subgroup could be attributed to cochlear implant processing, whereas channel interaction played a much smaller role in determining performance errors. The study also showed that large changes to channel number in the Advanced Combination Encoder signal processing strategy led to no substantial changes in performance.

Recognition Memory for Realistic Synthetic Faces

PubMed Central

Yotsumoto, Yuko; Kahana, Michael J.; Wilson, Hugh R.; Sekuler, Robert

2006-01-01

A series of experiments examined short-term recognition memory for trios of briefly-presented, synthetic human faces derived from three real human faces. The stimuli were graded series of faces, which differed by varying known amounts from the face of the average female. Faces based on each of the three real faces were transformed so as to lie along orthogonal axes in a 3-D face space. Experiment 1 showed that the synthetic faces' perceptual similarity stucture strongly influenced recognition memory. Results were fit by NEMo, a noisy exemplar model of perceptual recognition memory. The fits revealed that recognition memory was influenced both by the similarity of the probe to series items, and by the similarities among the series items themselves. Non-metric multi-dimensional scaling (MDS) showed that faces' perceptual representations largely preserved the 3-D space in which the face stimuli were arrayed. NEMo gave a better account of the results when similarity was defined as perceptual, MDS similarity rather than physical proximity of one face to another. Experiment 2 confirmed the importance of within-list homogeneity directly, without mediation of a model. We discuss the affinities and differences between visual memory for synthetic faces and memory for simpler stimuli. PMID:17948069

Programmable assembly of nanoarchitectures using genetically engineered viruses.

PubMed

Huang, Yu; Chiang, Chung-Yi; Lee, Soo Kwan; Gao, Yan; Hu, Evelyn L; De Yoreo, James; Belcher, Angela M

2005-07-01

Biological systems possess inherent molecular recognition and self-assembly capabilities and are attractive templates for constructing complex material structures with molecular precision. Here we report the assembly of various nanoachitectures including nanoparticle arrays, hetero-nanoparticle architectures, and nanowires utilizing highly engineered M13 bacteriophage as templates. The genome of M13 phage can be rationally engineered to produce viral particles with distinct substrate-specific peptides expressed on the filamentous capsid and the ends, providing a generic template for programmable assembly of complex nanostructures. Phage clones with gold-binding motifs on the capsid and streptavidin-binding motifs at one end are created and used to assemble Au and CdSe nanocrytals into ordered one-dimensional arrays and more complex geometries. Initial studies show such nanoparticle arrays can further function as templates to nucleate highly conductive nanowires that are important for addressing/interconnecting individual nanostructures.

Use of array of conducting polymers for differentiation of coconut oil products.

PubMed

Rañola, Rey Alfred G; Santiago, Karen S; Sevilla, Fortunato B

2016-01-01

An array of chemiresistors based on conducting polymers was assembled for the differentiation of coconut oil products. The chemiresistor sensors were fabricated through the potentiostatic electrodeposition of polyaniline (PANi), polypyrrole (PPy) and poly(3-methylthiophene) (P-3MTp) on the gap separating two planar gold electrodes set on a Teflon substrate. The change in electrical resistance of the sensors was measured and observed after exposing the array to the headspace of oil samples. The sensor response was found rapid, reversible and reproducible. Different signals were obtained for each coconut oil sample and pattern recognition techniques were employed for the analysis of the data. The developed system was able to distinguish virgin coconut oil (VCO) from refined, bleached & deodorised coconut oil (RBDCO), flavoured VCO, homemade VCO, and rancid VCO. Copyright © 2015 Elsevier B.V. All rights reserved.

"Anticlumping" and Other Combinatorial Effects on Clumped Isotopes: Implications for Tracing Biogeochemical Cycling

NASA Astrophysics Data System (ADS)

Yeung, L.

2015-12-01

I present a mode of isotopic ordering that has purely combinatorial origins. It can be important when identical rare isotopes are paired by coincidence (e.g., they are neighbors on the same molecule), or when extrinsic factors govern the isotopic composition of the two atoms that share a chemical bond. By itself, combinatorial isotope pairing yields products with isotopes either randomly distributed or with a deficit relative to a random distribution of isotopes. These systematics arise because of an unconventional coupling between the formation of singly- and multiply-substituted isotopic moieties. In a random distribution, rare isotopes are symmetrically distributed: Single isotopic substitutions (e.g., H‒D and D‒H in H2) occur with equal probability, and double isotopic substitutions (e.g., D2) occur according to random chance. The absence of symmetry in a bond-making complex can yield unequal numbers of singly-substituted molecules (e.g., more H‒D than D‒H in H2), which is recorded in the product molecule as a deficit in doubly-substituted moieties and an "anticlumped" isotope distribution (i.e., Δn < 0). Enzymatic isotope pairing reactions, which can have site-specific isotopic fractionation factors and atom reservoirs, should express this class of combinatorial isotope effect. Chemical-kinetic isotope effects, which are related to the bond-forming transition state, arise independently and express second-order combinatorial effects. In general, both combinatorial and chemical factors are important for calculating and interpreting clumped-isotope signatures of individual reactions. In many reactions relevant to geochemical oxygen, carbon, and nitrogen cycling, combinatorial isotope pairing likely plays a strong role in the clumped isotope distribution of the products. These isotopic signatures, manifest as either directly bound isotope clumps or as features of a molecule's isotopic anatomy, could be exploited as tracers of biogeochemistry that can relate molecular mechanisms to signals observable at environmentally relevant spatial scales.

Balancing focused combinatorial libraries based on multiple GPCR ligands

NASA Astrophysics Data System (ADS)

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.

Creative thought as blind-variation and selective-retention: Combinatorial models of exceptional creativity

NASA Astrophysics Data System (ADS)

Simonton, Dean Keith

2010-06-01

Campbell (1960) proposed that creative thought should be conceived as a blind-variation and selective-retention process (BVSR). This article reviews the developments that have taken place in the half century that has elapsed since his proposal, with special focus on the use of combinatorial models as formal representations of the general theory. After defining the key concepts of blind variants, creative thought, and disciplinary context, the combinatorial models are specified in terms of individual domain samples, variable field size, ideational combination, and disciplinary communication. Empirical implications are then derived with respect to individual, domain, and field systems. These abstract combinatorial models are next provided substantive reinforcement with respect to findings concerning the cognitive processes, personality traits, developmental factors, and social contexts that contribute to creativity. The review concludes with some suggestions regarding future efforts to explicate creativity according to BVSR theory.

Combinatorial Color Space Models for Skin Detection in Sub-continental Human Images

NASA Astrophysics Data System (ADS)

Khaled, Shah Mostafa; Saiful Islam, Md.; Rabbani, Md. Golam; Tabassum, Mirza Rehenuma; Gias, Alim Ul; Kamal, Md. Mostafa; Muctadir, Hossain Muhammad; Shakir, Asif Khan; Imran, Asif; Islam, Saiful

Among different color models HSV, HLS, YIQ, YCbCr, YUV, etc. have been most popular for skin detection. Most of the research done in the field of skin detection has been trained and tested on human images of African, Mongolian and Anglo-Saxon ethnic origins, skin colors of Indian sub-continentals have not been focused separately. Combinatorial algorithms, without affecting asymptotic complexity can be developed using the skin detection concepts of these color models for boosting detection performance. In this paper a comparative study of different combinatorial skin detection algorithms have been made. For training and testing 200 images (skin and non skin) containing pictures of sub-continental male and females have been used to measure the performance of the combinatorial approaches, and considerable development in success rate with True Positive of 99.5% and True Negative of 93.3% have been observed.

Optimized Reaction Conditions for Amide Bond Formation in DNA-Encoded Combinatorial Libraries.

PubMed

Li, Yizhou; Gabriele, Elena; Samain, Florent; Favalli, Nicholas; Sladojevich, Filippo; Scheuermann, Jörg; Neri, Dario

2016-08-08

DNA-encoded combinatorial libraries are increasingly being used as tools for the discovery of small organic binding molecules to proteins of biological or pharmaceutical interest. In the majority of cases, synthetic procedures for the formation of DNA-encoded combinatorial libraries incorporate at least one step of amide bond formation between amino-modified DNA and a carboxylic acid. We investigated reaction conditions and established a methodology by using 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide, 1-hydroxy-7-azabenzotriazole and N,N'-diisopropylethylamine (EDC/HOAt/DIPEA) in combination, which provided conversions greater than 75% for 423/543 (78%) of the carboxylic acids tested. These reaction conditions were efficient with a variety of primary and secondary amines, as well as with various types of amino-modified oligonucleotides. The reaction conditions, which also worked efficiently over a broad range of DNA concentrations and reaction scales, should facilitate the synthesis of novel DNA-encoded combinatorial libraries.

Combinatorial games with a pass: a dynamical systems approach.

PubMed

Morrison, Rebecca E; Friedman, Eric J; Landsberg, Adam S

2011-12-01

By treating combinatorial games as dynamical systems, we are able to address a longstanding open question in combinatorial game theory, namely, how the introduction of a "pass" move into a game affects its behavior. We consider two well known combinatorial games, 3-pile Nim and 3-row Chomp. In the case of Nim, we observe that the introduction of the pass dramatically alters the game's underlying structure, rendering it considerably more complex, while for Chomp, the pass move is found to have relatively minimal impact. We show how these results can be understood by recasting these games as dynamical systems describable by dynamical recursion relations. From these recursion relations, we are able to identify underlying structural connections between these "games with passes" and a recently introduced class of "generic (perturbed) games." This connection, together with a (non-rigorous) numerical stability analysis, allows one to understand and predict the effect of a pass on a game.

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

PubMed

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.

Method for automatic detection of wheezing in lung sounds.

PubMed

Riella, R J; Nohama, P; Maia, J M

2009-07-01

The present report describes the development of a technique for automatic wheezing recognition in digitally recorded lung sounds. This method is based on the extraction and processing of spectral information from the respiratory cycle and the use of these data for user feedback and automatic recognition. The respiratory cycle is first pre-processed, in order to normalize its spectral information, and its spectrogram is then computed. After this procedure, the spectrogram image is processed by a two-dimensional convolution filter and a half-threshold in order to increase the contrast and isolate its highest amplitude components, respectively. Thus, in order to generate more compressed data to automatic recognition, the spectral projection from the processed spectrogram is computed and stored as an array. The higher magnitude values of the array and its respective spectral values are then located and used as inputs to a multi-layer perceptron artificial neural network, which results an automatic indication about the presence of wheezes. For validation of the methodology, lung sounds recorded from three different repositories were used. The results show that the proposed technique achieves 84.82% accuracy in the detection of wheezing for an isolated respiratory cycle and 92.86% accuracy for the detection of wheezes when detection is carried out using groups of respiratory cycles obtained from the same person. Also, the system presents the original recorded sound and the post-processed spectrogram image for the user to draw his own conclusions from the data.

Perceptual Learning of Object Shape

PubMed Central

Golcu, Doruk; Gilbert, Charles D.

2009-01-01

Recognition of objects is accomplished through the use of cues that depend on internal representations of familiar shapes. We used a paradigm of perceptual learning during visual search to explore what features human observers use to identify objects. Human subjects were trained to search for a target object embedded in an array of distractors, until their performance improved from near-chance levels to over 80% of trials in an object specific manner. We determined the role of specific object components in the recognition of the object as a whole by measuring the transfer of learning from the trained object to other objects sharing components with it. Depending on the geometric relationship of the trained object with untrained objects, transfer to untrained objects was observed. Novel objects that shared a component with the trained object were identified at much higher levels than those that did not, and this could be used as an indicator of which features of the object were important for recognition. Training on an object also transferred to the components of the object when these components were embedded in an array of distractors of similar complexity. These results suggest that objects are not represented in a holistic manner during learning, but that their individual components are encoded. Transfer between objects was not complete, and occurred for more than one component, regardless of how well they distinguish the object from distractors. This suggests that a joint involvement of multiple components was necessary for full performance. PMID:19864574

Optical signal processing

NASA Technical Reports Server (NTRS)

Casasent, D.

1978-01-01

The article discusses several optical configurations used for signal processing. Electronic-to-optical transducers are outlined, noting fixed window transducers and moving window acousto-optic transducers. Folded spectrum techniques are considered, with reference to wideband RF signal analysis, fetal electroencephalogram analysis, engine vibration analysis, signal buried in noise, and spatial filtering. Various methods for radar signal processing are described, such as phased-array antennas, the optical processing of phased-array data, pulsed Doppler and FM radar systems, a multichannel one-dimensional optical correlator, correlations with long coded waveforms, and Doppler signal processing. Means for noncoherent optical signal processing are noted, including an optical correlator for speech recognition and a noncoherent optical correlator.

Using speech recognition to enhance the Tongue Drive System functionality in computer access.

PubMed

Huo, Xueliang; Ghovanloo, Maysam

2011-01-01

Tongue Drive System (TDS) is a wireless tongue operated assistive technology (AT), which can enable people with severe physical disabilities to access computers and drive powered wheelchairs using their volitional tongue movements. TDS offers six discrete commands, simultaneously available to the users, for pointing and typing as a substitute for mouse and keyboard in computer access, respectively. To enhance the TDS performance in typing, we have added a microphone, an audio codec, and a wireless audio link to its readily available 3-axial magnetic sensor array, and combined it with a commercially available speech recognition software, the Dragon Naturally Speaking, which is regarded as one of the most efficient ways for text entry. Our preliminary evaluations indicate that the combined TDS and speech recognition technologies can provide end users with significantly higher performance than using each technology alone, particularly in completing tasks that require both pointing and text entry, such as web surfing.

An optical processor for object recognition and tracking

NASA Technical Reports Server (NTRS)

Sloan, J.; Udomkesmalee, S.

1987-01-01

The design and development of a miniaturized optical processor that performs real time image correlation are described. The optical correlator utilizes the Vander Lugt matched spatial filter technique. The correlation output, a focused beam of light, is imaged onto a CMOS photodetector array. In addition to performing target recognition, the device also tracks the target. The hardware, composed of optical and electro-optical components, occupies only 590 cu cm of volume. A complete correlator system would also include an input imaging lens. This optical processing system is compact, rugged, requires only 3.5 watts of operating power, and weighs less than 3 kg. It represents a major achievement in miniaturizing optical processors. When considered as a special-purpose processing unit, it is an attractive alternative to conventional digital image recognition processing. It is conceivable that the combined technology of both optical and ditital processing could result in a very advanced robot vision system.

Structure-based design of combinatorial mutagenesis libraries

PubMed Central

Verma, Deeptak; Grigoryan, Gevorg; Bailey-Kellogg, Chris

2015-01-01

The development of protein variants with improved properties (thermostability, binding affinity, catalytic activity, etc.) has greatly benefited from the application of high-throughput screens evaluating large, diverse combinatorial libraries. At the same time, since only a very limited portion of sequence space can be experimentally constructed and tested, an attractive possibility is to use computational protein design to focus libraries on a productive portion of the space. We present a general-purpose method, called “Structure-based Optimization of Combinatorial Mutagenesis” (SOCoM), which can optimize arbitrarily large combinatorial mutagenesis libraries directly based on structural energies of their constituents. SOCoM chooses both positions and substitutions, employing a combinatorial optimization framework based on library-averaged energy potentials in order to avoid explicitly modeling every variant in every possible library. In case study applications to green fluorescent protein, β-lactamase, and lipase A, SOCoM optimizes relatively small, focused libraries whose variants achieve energies comparable to or better than previous library design efforts, as well as larger libraries (previously not designable by structure-based methods) whose variants cover greater diversity while still maintaining substantially better energies than would be achieved by representative random library approaches. By allowing the creation of large-scale combinatorial libraries based on structural calculations, SOCoM promises to increase the scope of applicability of computational protein design and improve the hit rate of discovering beneficial variants. While designs presented here focus on variant stability (predicted by total energy), SOCoM can readily incorporate other structure-based assessments, such as the energy gap between alternative conformational or bound states. PMID:25611189

Structure-based design of combinatorial mutagenesis libraries.

PubMed

Verma, Deeptak; Grigoryan, Gevorg; Bailey-Kellogg, Chris

2015-05-01

The development of protein variants with improved properties (thermostability, binding affinity, catalytic activity, etc.) has greatly benefited from the application of high-throughput screens evaluating large, diverse combinatorial libraries. At the same time, since only a very limited portion of sequence space can be experimentally constructed and tested, an attractive possibility is to use computational protein design to focus libraries on a productive portion of the space. We present a general-purpose method, called "Structure-based Optimization of Combinatorial Mutagenesis" (SOCoM), which can optimize arbitrarily large combinatorial mutagenesis libraries directly based on structural energies of their constituents. SOCoM chooses both positions and substitutions, employing a combinatorial optimization framework based on library-averaged energy potentials in order to avoid explicitly modeling every variant in every possible library. In case study applications to green fluorescent protein, β-lactamase, and lipase A, SOCoM optimizes relatively small, focused libraries whose variants achieve energies comparable to or better than previous library design efforts, as well as larger libraries (previously not designable by structure-based methods) whose variants cover greater diversity while still maintaining substantially better energies than would be achieved by representative random library approaches. By allowing the creation of large-scale combinatorial libraries based on structural calculations, SOCoM promises to increase the scope of applicability of computational protein design and improve the hit rate of discovering beneficial variants. While designs presented here focus on variant stability (predicted by total energy), SOCoM can readily incorporate other structure-based assessments, such as the energy gap between alternative conformational or bound states. © 2015 The Protein Society.

Images of Women in Chinese Literature. Volume 1.

ERIC Educational Resources Information Center

Yu-ning, Li, Ed.

This book examines the ways in which Chinese literature offers a vast array of prospects, new interpretations, new fields of study, and new themes for the study of women. As a result of the global movement toward greater recognition of gender equality and human dignity, the study of women as portrayed in Chinese literature has a long and rich…

Visual-Attentional Span and Lexical ­Decision in Skilled Adult Readers

ERIC Educational Resources Information Center

Holmes, Virginia M.; Dawson, Georgia

2014-01-01

The goal of the study was to examine the association between visual-attentional span and lexical decision in skilled adult readers. In the span tasks, an array of letters was presented briefly and recognition or production of a single cued letter (partial span) or production of all letters (whole span) was required. Independently of letter…

Matching Faces to Photographs: Poor Performance in Eyewitness Memory (without the Memory)

ERIC Educational Resources Information Center

Megreya, Ahmed M.; Burton, A. Mike

2008-01-01

Eyewitness memory is known to be fallible. We describe 3 experiments that aim to establish baseline performance for recognition of unfamiliar faces. In Experiment 1, viewers were shown live actors or photos (targets), and then immediately presented with arrays of 10 faces (test items). Asked whether the target was present among the test items, and…

A Distinctive Theory of Teaching and Learning for Older Learners: Why and Why Not?

ERIC Educational Resources Information Center

Tam, Maureen

2014-01-01

In the wake of the world's fast-growing ageing populations and the increasing recognition of the benefits of later life learning towards successful ageing, opportunities for elders and senior persons to engage in learning have proliferated, resulting in an array of programmes and activities being planned and organized by governments,…

Transport of calcium ions through a bulk membrane by use of a dynamic combinatorial library.

PubMed

Saggiomo, Vittorio; Lüning, Ulrich

2009-07-07

In a bulk membrane transport experiment, a dynamic combinatorial library (DCL) has been used to transport calcium ions; the calcium ions amplify the formation of a macrocyclic carrier which results in transport.

Counting Pizza Pieces and Other Combinatorial Problems.

ERIC Educational Resources Information Center

Maier, Eugene

1988-01-01

The general combinatorial problem of counting the number of regions into which the interior of a circle is divided by a family of lines is considered. A general formula is developed and its use is illustrated in two situations. (PK)

On the existence of binary simplex codes. [using combinatorial construction

NASA Technical Reports Server (NTRS)

Taylor, H.

1977-01-01

Using a simple combinatorial construction, the existence of a binary simplex code with m codewords for all m is greater than or equal to 1 is proved. The problem of the shortest possible length is left open.

Application of combinatorial biocatalysis for a unique ring expansion of dihydroxymethylzearalenone

USDA-ARS?s Scientific Manuscript database

Combinatorial biocatalysis was applied to generate a diverse set of dihydroxymethylzearalenone derivatives with modified ring structure. In one chemoenzymatic reaction sequence, dihydroxymethylzearalenone was first subjected to a unique enzyme-catalyzed oxidative ring opening reaction that creates ...

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

PubMed

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.

Dragon Ears airborne acoustic array: CSP analysis applied to cross array to compute real-time 2D acoustic sound field

NASA Astrophysics Data System (ADS)

Cerwin, Steve; Barnes, Julie; Kell, Scott; Walters, Mark

2003-09-01

This paper describes development and application of a novel method to accomplish real-time solid angle acoustic direction finding using two 8-element orthogonal microphone arrays. The developed prototype system was intended for localization and signature recognition of ground-based sounds from a small UAV. Recent advances in computer speeds have enabled the implementation of microphone arrays in many audio applications. Still, the real-time presentation of a two-dimensional sound field for the purpose of audio target localization is computationally challenging. In order to overcome this challenge, a crosspower spectrum phase1 (CSP) technique was applied to each 8-element arm of a 16-element cross array to provide audio target localization. In this paper, we describe the technique and compare it with two other commonly used techniques; Cross-Spectral Matrix2 and MUSIC3. The results show that the CSP technique applied to two 8-element orthogonal arrays provides a computationally efficient solution with reasonable accuracy and tolerable artifacts, sufficient for real-time applications. Additional topics include development of a synchronized 16-channel transmitter and receiver to relay the airborne data to the ground-based processor and presentation of test data demonstrating both ground-mounted operation and airborne localization of ground-based gunshots and loud engine sounds.

Analyte species and concentration identification using differentially functionalized microcantilever arrays and artificial neural networks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Senesac, Larry R; Datskos, Panos G; Sepaniak, Michael J

2006-01-01

In the present work, we have performed analyte species and concentration identification using an array of ten differentially functionalized microcantilevers coupled with a back-propagation artificial neural network pattern recognition algorithm. The array consists of ten nanostructured silicon microcantilevers functionalized by polymeric and gas chromatography phases and macrocyclic receptors as spatially dense, differentially responding sensing layers for identification and quantitation of individual analyte(s) and their binary mixtures. The array response (i.e. cantilever bending) to analyte vapor was measured by an optical readout scheme and the responses were recorded for a selection of individual analytes as well as several binary mixtures. Anmore » artificial neural network (ANN) was designed and trained to recognize not only the individual analytes and binary mixtures, but also to determine the concentration of individual components in a mixture. To the best of our knowledge, ANNs have not been applied to microcantilever array responses previously to determine concentrations of individual analytes. The trained ANN correctly identified the eleven test analyte(s) as individual components, most with probabilities greater than 97%, whereas it did not misidentify an unknown (untrained) analyte. Demonstrated unique aspects of this work include an ability to measure binary mixtures and provide both qualitative (identification) and quantitative (concentration) information with array-ANN-based sensor methodologies.« less

One-Bead-Two-Compound Thioether Bridged Macrocyclic γ-AApeptide Screening Library against EphA2.

PubMed

Shi, Yan; Challa, Sridevi; Sang, Peng; She, Fengyu; Li, Chunpu; Gray, Geoffrey M; Nimmagadda, Alekhya; Teng, Peng; Odom, Timothy; Wang, Yan; van der Vaart, Arjan; Li, Qi; Cai, Jianfeng

2017-11-22

Identification of molecular ligands that recognize peptides or proteins is significant but poses a fundamental challenge in chemical biology and biomedical sciences. Development of cyclic peptidomimetic library is scarce, and thus discovery of cyclic peptidomimetic ligands for protein targets is rare. Herein we report the unprecedented one-bead-two-compound (OBTC) combinatorial library based on a novel class of the macrocyclic peptidomimetics γ-AApeptides. In the library, we utilized the coding peptide tags synthesized with Dde-protected α-amino acids, which were orthogonal to solid phase synthesis of γ-AApeptides. Employing the thioether linkage, the desired macrocyclic γ-AApeptides were found to be effective for ligand identification. Screening the library against the receptor tyrosine kinase EphA2 led to the discovery of one lead compound that tightly bound to EphA2 (K d = 81 nM) and potently antagonized EphA2-mediated signaling. This new approach of macrocyclic peptidomimetic library may lead to a novel platform for biomacromolecular surface recognition and function modulation.

Identifying the preferred RNA motifs and chemotypes that interact by probing millions of combinations.

PubMed

Tran, Tuan; Disney, Matthew D

2012-01-01

RNA is an important therapeutic target but information about RNA-ligand interactions is limited. Here, we report a screening method that probes over 3,000,000 combinations of RNA motif-small molecule interactions to identify the privileged RNA structures and chemical spaces that interact. Specifically, a small molecule library biased for binding RNA was probed for binding to over 70,000 unique RNA motifs in a high throughput solution-based screen. The RNA motifs that specifically bind each small molecule were identified by microarray-based selection. In this library-versus-library or multidimensional combinatorial screening approach, hairpin loops (among a variety of RNA motifs) were the preferred RNA motif space that binds small molecules. Furthermore, it was shown that indole, 2-phenyl indole, 2-phenyl benzimidazole and pyridinium chemotypes allow for specific recognition of RNA motifs. As targeting RNA with small molecules is an extremely challenging area, these studies provide new information on RNA-ligand interactions that has many potential uses.

Identifying the Preferred RNA Motifs and Chemotypes that Interact by Probing Millions of Combinations

PubMed Central

Tran, Tuan; Disney, Matthew D.

2012-01-01

RNA is an important therapeutic target but information about RNA-ligand interactions is limited. Here we report a screening method that probes over 3,000,000 combinations of RNA motif-small molecule interactions to identify the privileged RNA structures and chemical spaces that interact. Specifically, a small molecule library biased for binding RNA was probed for binding to over 70,000 unique RNA motifs in a high throughput solution-based screen. The RNA motifs that specifically bind each small molecule were identified by microarray-based selection. In this library-versus-library or multidimensional combinatorial screening approach, hairpin loops (amongst a variety of RNA motifs) were the preferred RNA motif space that binds small molecules. Furthermore, it was shown that indole, 2-phenyl indole, 2-phenyl benzimidazole, and pyridinium chemotypes allow for specific recognition of RNA motifs. Since targeting RNA with small molecules is an extremely challenging area, these studies provide new information on RNA-ligand interactions that has many potential uses. PMID:23047683

Probing a 2-aminobenzimidazole library for binding to RNA internal loops via two-dimensional combinatorial screening.

PubMed

Velagapudi, Sai Pradeep; Pushechnikov, Alexei; Labuda, Lucas P; French, Jonathan M; Disney, Matthew D

2012-11-16

There are many potential RNA drug targets in bacterial, viral, and human transcriptomes. However, there are few small molecules that modulate RNA function. This is due, in part, to a lack of fundamental understanding about RNA-ligand interactions including the types of small molecules that bind to RNA structural elements and the RNA structural elements that bind to small molecules. In an effort to better understand RNA-ligand interactions, we diversified the 2-aminobenzimidazole core (2AB) and probed the resulting library for binding to a library of RNA internal loops. We chose the 2AB core for these studies because it is a privileged scaffold for binding RNA based on previous reports. These studies identified that N-methyl pyrrolidine, imidazole, and propylamine diversity elements at the R1 position increase binding to internal loops; variability at the R2 position is well tolerated. The preferred RNA loop space was also determined for five ligands using a statistical approach and identified trends that lead to selective recognition.

A characterization of horizontal visibility graphs and combinatorics on words

NASA Astrophysics Data System (ADS)

Gutin, Gregory; Mansour, Toufik; Severini, Simone

2011-06-01

A Horizontal Visibility Graph (HVG) is defined in association with an ordered set of non-negative reals. HVGs realize a methodology in the analysis of time series, their degree distribution being a good discriminator between randomness and chaos Luque et al. [B. Luque, L. Lacasa, F. Ballesteros, J. Luque, Horizontal visibility graphs: exact results for random time series, Phys. Rev. E 80 (2009), 046103]. We prove that a graph is an HVG if and only if it is outerplanar and has a Hamilton path. Therefore, an HVG is a noncrossing graph, as defined in algebraic combinatorics Flajolet and Noy [P. Flajolet, M. Noy, Analytic combinatorics of noncrossing configurations, Discrete Math., 204 (1999) 203-229]. Our characterization of HVGs implies a linear time recognition algorithm. Treating ordered sets as words, we characterize subfamilies of HVGs highlighting various connections with combinatorial statistics and introducing the notion of a visible pair. With this technique, we determine asymptotically the average number of edges of HVGs.

Recognition of Antigen-Specific B Cell Receptors From Chronic Lymphocytic Leukemia Patients By Synthetic Antigen Surrogates

PubMed Central

Sarkar, Mohosin; Liu, Yun; Morimoto, Jumpei; Peng, Haiyong; Aquino, Claudio; Rader, Christoph; Chiorazzi, Nicholas

2014-01-01

In patients with chronic lymphocytic leukemia (CLL), a single neoplastic antigen-specific B cell accumulates and overgrows other B cells, leading to immune deficiency. CLL is often treated with drugs that ablate all B cells, leading to further weakening of humoral immunity, and a more focused therapeutic strategy capable of targeting only the pathogenic B cells would represent a significant advance. One approach to this would be to develop synthetic surrogates of the CLL antigens allowing differentiation of the CLL cells and healthy B cells in a patient. Here, we describe discovery of non-peptidic molecules capable of targeting antigen-specific B cell receptors with good affinity and selectivity using a combinatorial library screen. We demonstrate that our hit compounds act as synthetic antigen surrogates and recognize CLL cells and not healthy B cells. Additionally, we argue that the technology we developed can be used for discovery of other classes of antigen surrogates. PMID:25467125

A thorough experimental study of CH/π interactions in water: quantitative structure-stability relationships for carbohydrate/aromatic complexes.

PubMed

Jiménez-Moreno, Ester; Jiménez-Osés, Gonzalo; Gómez, Ana M; Santana, Andrés G; Corzana, Francisco; Bastida, Agatha; Jiménez-Barbero, Jesus; Asensio, Juan Luis

2015-11-13

CH/π interactions play a key role in a large variety of molecular recognition processes of biological relevance. However, their origins and structural determinants in water remain poorly understood. In order to improve our comprehension of these important interaction modes, we have performed a quantitative experimental analysis of a large data set comprising 117 chemically diverse carbohydrate/aromatic stacking complexes, prepared through a dynamic combinatorial approach recently developed by our group. The obtained free energies provide a detailed picture of the structure-stability relationships that govern the association process, opening the door to the rational design of improved carbohydrate-based ligands or carbohydrate receptors. Moreover, this experimental data set, supported by quantum mechanical calculations, has contributed to the understanding of the main driving forces that promote complex formation, underlining the key role played by coulombic and solvophobic forces on the stabilization of these complexes. This represents the most quantitative and extensive experimental study reported so far for CH/π complexes in water.

My journey into the world of sphingolipids and sphingolipidoses

PubMed Central

SANDHOFF, Konrad

2012-01-01

Analysis of lipid storage in postmortem brains of patients with amaurotic idiocy led to the recognition of five lysosomal ganglioside storage diseases and identification of their inherited metabolic blocks. Purification of lysosomal acid sphingomyelinase and ceramidase and analysis of their gene structures were the prerequisites for the clarification of Niemann-Pick and Farber disease. For lipid catabolism, intraendosomal vesicles are formed during the endocytotic pathway. They are subjected to lipid sorting processes and were identified as luminal platforms for cellular lipid and membrane degradation. Lipid binding glycoproteins solubilize lipids from these cholesterol poor membranes and present them to water-soluble hydrolases for digestion. Biosynthesis and intracellular trafficking of lysosomal hydrolases (hexosaminidases, acid sphingomyelinase and ceramidase) and lipid binding and transfer proteins (GM2 activator, saposins) were analyzed to identify the molecular and metabolic basis of several sphingolipidoses. Studies on the biosynthesis of glycosphingolipids yielded the scheme of Combinatorial Ganglioside Biosynthesis involving promiscuous glycosyltransferases. Their defects in mutagenized mice impair brain development and function. PMID:23229750

Joining the dots - protein-RNA interactions mediating local mRNA translation in neurons.

PubMed

Gallagher, Christopher; Ramos, Andres

2018-06-01

Establishing and maintaining the complex network of connections required for neuronal communication requires the transport and in situ translation of large groups of mRNAs to create local proteomes. In this Review, we discuss the regulation of local mRNA translation in neurons and the RNA-binding proteins that recognise RNA zipcode elements and connect the mRNAs to the cellular transport networks, as well as regulate their translation control. However, mRNA recognition by the regulatory proteins is mediated by the combinatorial action of multiple RNA-binding domains. This increases the specificity and affinity of the interaction, while allowing the protein to recognise a diverse set of targets and mediate a range of mechanisms for translational regulation. The structural and molecular understanding of the interactions can be used together with novel microscopy and transcriptome-wide data to build a mechanistic framework for the regulation of local mRNA translation. © 2018 Federation of European Biochemical Societies.

Recognition of antigen-specific B-cell receptors from chronic lymphocytic leukemia patients by synthetic antigen surrogates.

PubMed

Sarkar, Mohosin; Liu, Yun; Morimoto, Jumpei; Peng, Haiyong; Aquino, Claudio; Rader, Christoph; Chiorazzi, Nicholas; Kodadek, Thomas

2014-12-18

In patients with chronic lymphocytic leukemia (CLL), a single neoplastic antigen-specific B cell accumulates and overgrows other B cells, leading to immune deficiency. CLL is often treated with drugs that ablate all B cells, leading to further weakening of humoral immunity, and a more focused therapeutic strategy capable of targeting only the pathogenic B cells would represent a significant advance. One approach to this would be to develop synthetic surrogates of the CLL antigens allowing differentiation of the CLL cells and healthy B cells in a patient. Here, we describe nonpeptidic molecules capable of targeting antigen-specific B cell receptors with good affinity and selectivity using a combinatorial library screen. We demonstrate that our hit compounds act as synthetic antigen surrogates and recognize CLL cells and not healthy B cells. Additionally, we argue that the technology we developed can be used to identify other classes of antigen surrogates. Copyright © 2014 Elsevier Ltd. All rights reserved.

Mapping the Materials Genome through Combinatorial Informatics

NASA Astrophysics Data System (ADS)

Rajan, Krishna

2012-02-01

The recently announced White House Materials Genome Initiative provides an exciting challenge to the materials science community. To meet that challenge one needs to address a critical question, namely what is the materials genome? Some guide on how to the answer this question can be gained by recognizing that a ``gene'' is a carrier of information. In the biological sciences, discovering how to manipulate these genes has generated exciting discoveries in fundamental molecular biology as well as significant advances in biotechnology. Scaling that up to molecular, cellular length scales and beyond, has spawned from genomics, fields such as proteomics, metabolomics and essentially systems biology. The ``omics'' approach requires that one needs to discover and track these ``carriers of information'' and then correlate that information to predict behavior. A similar challenge lies in materials science, where there is a diverse array of modalities of materials ``discovery'' ranging from new materials chemistries and molecular arrangements with novel properties, to the development and design of new micro- and mesoscale structures. Hence to meaningfully adapt the spirit of ``genomics'' style research in materials science, we need to first identify and map the ``genes'' across different materials science applications On the experimental side, combinatorial experiments have opened a new approach to generate data in a high throughput manner, but without a clear way to link that to models, the full value of that data is not realized. Hence along with experimental and computational materials science, we need to add a ``third leg'' to our toolkit to make the ``Materials Genome'' a reality, the science of Materials Informatics. In this presentation we provide an overview of how information science coupled to materials science can in fact achieve the goal of mapping the ``Materials Genome''.

Automated Lead Optimization of MMP-12 Inhibitors Using a Genetic Algorithm.

PubMed

Pickett, Stephen D; Green, Darren V S; Hunt, David L; Pardoe, David A; Hughes, Ian

2011-01-13

Traditional lead optimization projects involve long synthesis and testing cycles, favoring extensive structure-activity relationship (SAR) analysis and molecular design steps, in an attempt to limit the number of cycles that a project must run to optimize a development candidate. Microfluidic-based chemistry and biology platforms, with cycle times of minutes rather than weeks, lend themselves to unattended autonomous operation. The bottleneck in the lead optimization process is therefore shifted from synthesis or test to SAR analysis and design. As such, the way is open to an algorithm-directed process, without the need for detailed user data analysis. Here, we present results of two synthesis and screening experiments, undertaken using traditional methodology, to validate a genetic algorithm optimization process for future application to a microfluidic system. The algorithm has several novel features that are important for the intended application. For example, it is robust to missing data and can suggest compounds for retest to ensure reliability of optimization. The algorithm is first validated on a retrospective analysis of an in-house library embedded in a larger virtual array of presumed inactive compounds. In a second, prospective experiment with MMP-12 as the target protein, 140 compounds are submitted for synthesis over 10 cycles of optimization. Comparison is made to the results from the full combinatorial library that was synthesized manually and tested independently. The results show that compounds selected by the algorithm are heavily biased toward the more active regions of the library, while the algorithm is robust to both missing data (compounds where synthesis failed) and inactive compounds. This publication places the full combinatorial library and biological data into the public domain with the intention of advancing research into algorithm-directed lead optimization methods.

Automated Lead Optimization of MMP-12 Inhibitors Using a Genetic Algorithm

PubMed Central

2010-01-01

Traditional lead optimization projects involve long synthesis and testing cycles, favoring extensive structure−activity relationship (SAR) analysis and molecular design steps, in an attempt to limit the number of cycles that a project must run to optimize a development candidate. Microfluidic-based chemistry and biology platforms, with cycle times of minutes rather than weeks, lend themselves to unattended autonomous operation. The bottleneck in the lead optimization process is therefore shifted from synthesis or test to SAR analysis and design. As such, the way is open to an algorithm-directed process, without the need for detailed user data analysis. Here, we present results of two synthesis and screening experiments, undertaken using traditional methodology, to validate a genetic algorithm optimization process for future application to a microfluidic system. The algorithm has several novel features that are important for the intended application. For example, it is robust to missing data and can suggest compounds for retest to ensure reliability of optimization. The algorithm is first validated on a retrospective analysis of an in-house library embedded in a larger virtual array of presumed inactive compounds. In a second, prospective experiment with MMP-12 as the target protein, 140 compounds are submitted for synthesis over 10 cycles of optimization. Comparison is made to the results from the full combinatorial library that was synthesized manually and tested independently. The results show that compounds selected by the algorithm are heavily biased toward the more active regions of the library, while the algorithm is robust to both missing data (compounds where synthesis failed) and inactive compounds. This publication places the full combinatorial library and biological data into the public domain with the intention of advancing research into algorithm-directed lead optimization methods. PMID:24900251

Glucose enhancement of a facial recognition task in young adults.

PubMed

Metzger, M M

2000-02-01

Numerous studies have reported that glucose administration enhances memory processes in both elderly and young adult subjects. Although these studies have utilized a variety of procedures and paradigms, investigations of both young and elderly subjects have typically used verbal tasks (word list recall, paragraph recall, etc.). In the present study, the effect of glucose consumption on a nonverbal, facial recognition task in young adults was examined. Lemonade sweetened with either glucose (50 g) or saccharin (23.7 mg) was consumed by college students (mean age of 21.1 years) 15 min prior to a facial recognition task. The task consisted of a familiarization phase in which subjects were presented with "target" faces, followed immediately by a recognition phase in which subjects had to identify the targets among a random array of familiar target and novel "distractor" faces. Statistical analysis indicated that there were no differences on hit rate (target identification) for subjects who consumed either saccharin or glucose prior to the test. However, further analyses revealed that subjects who consumed glucose committed significantly fewer false alarms and had (marginally) higher d-prime scores (a signal detection measure) compared to subjects who consumed saccharin prior to the test. These results parallel a previous report demonstrating glucose enhancement of a facial recognition task in probable Alzheimer's patients; however, this is believed to be the first demonstration of glucose enhancement for a facial recognition task in healthy, young adults.

Multichannel Discriminative Detection of Explosive Vapors with an Array of Nanofibrous Membranes Loaded with Quantum Dots.

PubMed

Wu, Zhaofeng; Duan, Haiming; Li, Zhijun; Guo, Jixi; Zhong, Furu; Cao, Yali; Jia, Dianzeng

2017-11-20

The multichannel fluorescent sensor array based on nanofibrous membranes loaded with ZnS quantum dots (QDs) was created and demonstrated for the discriminative detection of explosives. The synergistic effect of the high surface-to-volume ratio of QDs, the good permeability of nanofibrous membranes and the differential response introduced by surface ligands was played by constructing the sensing array using nanofibrous membranes loaded with ZnS QDs featuring several surface ligands. Interestingly, although the fluorescence quenching of the nanofibrous membranes is not linearly related to the exposure time, the fingerprint of each explosive at different times is very similar in shape, and the fingerprints of the three explosives show different shapes. Three saturated vapors of nitroaromatic explosives could be reliably detected and discriminated by the array at room temperature. This work is the first step toward devising a monitoring system for explosives in the field of public security and defense. It could, for example, be coupled with the technology of image recognition and large data analysis for a rapid diagnostic test of explosives. This work further highlights the power of differential, multichannel arrays for the rapid and discriminative detection of a wide range of chemicals.

Multichannel Discriminative Detection of Explosive Vapors with an Array of Nanofibrous Membranes Loaded with Quantum Dots

PubMed Central

Wu, Zhaofeng; Duan, Haiming; Li, Zhijun; Guo, Jixi; Zhong, Furu; Cao, Yali; Jia, Dianzeng

2017-01-01

The multichannel fluorescent sensor array based on nanofibrous membranes loaded with ZnS quantum dots (QDs) was created and demonstrated for the discriminative detection of explosives. The synergistic effect of the high surface-to-volume ratio of QDs, the good permeability of nanofibrous membranes and the differential response introduced by surface ligands was played by constructing the sensing array using nanofibrous membranes loaded with ZnS QDs featuring several surface ligands. Interestingly, although the fluorescence quenching of the nanofibrous membranes is not linearly related to the exposure time, the fingerprint of each explosive at different times is very similar in shape, and the fingerprints of the three explosives show different shapes. Three saturated vapors of nitroaromatic explosives could be reliably detected and discriminated by the array at room temperature. This work is the first step toward devising a monitoring system for explosives in the field of public security and defense. It could, for example, be coupled with the technology of image recognition and large data analysis for a rapid diagnostic test of explosives. This work further highlights the power of differential, multichannel arrays for the rapid and discriminative detection of a wide range of chemicals. PMID:29156627

Kalman filter-based tracking of moving objects using linear ultrasonic sensor array for road vehicles

NASA Astrophysics Data System (ADS)

Li, Shengbo Eben; Li, Guofa; Yu, Jiaying; Liu, Chang; Cheng, Bo; Wang, Jianqiang; Li, Keqiang

2018-01-01

Detection and tracking of objects in the side-near-field has attracted much attention for the development of advanced driver assistance systems. This paper presents a cost-effective approach to track moving objects around vehicles using linearly arrayed ultrasonic sensors. To understand the detection characteristics of a single sensor, an empirical detection model was developed considering the shapes and surface materials of various detected objects. Eight sensors were arrayed linearly to expand the detection range for further application in traffic environment recognition. Two types of tracking algorithms, including an Extended Kalman filter (EKF) and an Unscented Kalman filter (UKF), for the sensor array were designed for dynamic object tracking. The ultrasonic sensor array was designed to have two types of fire sequences: mutual firing or serial firing. The effectiveness of the designed algorithms were verified in two typical driving scenarios: passing intersections with traffic sign poles or street lights, and overtaking another vehicle. Experimental results showed that both EKF and UKF had more precise tracking position and smaller RMSE (root mean square error) than a traditional triangular positioning method. The effectiveness also encourages the application of cost-effective ultrasonic sensors in the near-field environment perception in autonomous driving systems.

Running Clubs--A Combinatorial Investigation.

ERIC Educational Resources Information Center

Nissen, Phillip; Taylor, John

1991-01-01

Presented is a combinatorial problem based on the Hash House Harriers rule which states that the route of the run should not have previously been traversed by the club. Discovered is how many weeks the club can meet before the rule has to be broken. (KR)

Quantum Resonance Approach to Combinatorial Optimization

NASA Technical Reports Server (NTRS)

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.

Single-sensor multispeaker listening with acoustic metamaterials

PubMed Central

Xie, Yangbo; Tsai, Tsung-Han; Konneker, Adam; Popa, Bogdan-Ioan; Brady, David J.; Cummer, Steven A.

2015-01-01

Designing a “cocktail party listener” that functionally mimics the selective perception of a human auditory system has been pursued over the past decades. By exploiting acoustic metamaterials and compressive sensing, we present here a single-sensor listening device that separates simultaneous overlapping sounds from different sources. The device with a compact array of resonant metamaterials is demonstrated to distinguish three overlapping and independent sources with 96.67% correct audio recognition. Segregation of the audio signals is achieved using physical layer encoding without relying on source characteristics. This hardware approach to multichannel source separation can be applied to robust speech recognition and hearing aids and may be extended to other acoustic imaging and sensing applications. PMID:26261314

Compact optical processor for Hough and frequency domain features

NASA Astrophysics Data System (ADS)

Ott, Peter

1996-11-01

Shape recognition is necessary in a broad band of applications such as traffic sign or work piece recognition. It requires not only neighborhood processing of the input image pixels but global interconnection of them. The Hough transform (HT) performs such a global operation and it is well suited in the preprocessing stage of a shape recognition system. Translation invariant features can be easily calculated form the Hough domain. We have implemented on the computer a neural network shape recognition system which contains a HT, a feature extraction, and a classification layer. The advantage of this approach is that the total system can be optimized with well-known learning techniques and that it can explore the parallelism of the algorithms. However, the HT is a time consuming operation. Parallel, optical processing is therefore advantageous. Several systems have been proposed, based on space multiplexing with arrays of holograms and CGH's or time multiplexing with acousto-optic processors or by image rotation with incoherent and coherent astigmatic optical processors. We took up the last mentioned approach because 2D array detectors are read out line by line, so a 2D detector can achieve the same speed and is easier to implement. Coherent processing can allow the implementation of tilers in the frequency domain. Features based on wedge/ring, Gabor, or wavelet filters have been proven to show good discrimination capabilities for texture and shape recognition. The astigmatic lens system which is derived form the mathematical formulation of the HT is long and contains a non-standard, astigmatic element. By methods of lens transformation s for coherent applications we map the original design to a shorter lens with a smaller number of well separated standard elements and with the same coherent system response. The final lens design still contains the frequency plane for filtering and ray-tracing shows diffraction limited performance. Image rotation can be done optically by a rotating prism. We realize it on a fast FLC- SLM of our lab as input device. The filters can be implemented on the same type of SLM with 128 by 128 square pixels of size, resulting in a total length of the lens of less than 50cm.

Protein recognition by a pattern-generating fluorescent molecular probe.

PubMed

Pode, Zohar; Peri-Naor, Ronny; Georgeson, Joseph M; Ilani, Tal; Kiss, Vladimir; Unger, Tamar; Markus, Barak; Barr, Haim M; Motiei, Leila; Margulies, David

2017-12-01

Fluorescent molecular probes have become valuable tools in protein research; however, the current methods for using these probes are less suitable for analysing specific populations of proteins in their native environment. In this study, we address this gap by developing a unimolecular fluorescent probe that combines the properties of small-molecule-based probes and cross-reactive sensor arrays (the so-called chemical 'noses/tongues'). On the one hand, the probe can detect different proteins by generating unique identification (ID) patterns, akin to cross-reactive arrays. On the other hand, its unimolecular scaffold and selective binding enable this ID-generating probe to identify combinations of specific protein families within complex mixtures and to discriminate among isoforms in living cells, where macroscopic arrays cannot access. The ability to recycle the molecular device and use it to track several binding interactions simultaneously further demonstrates how this approach could expand the fluorescent toolbox currently used to detect and image proteins.

Gas Sensors Characterization and Multilayer Perceptron (MLP) Hardware Implementation for Gas Identification Using a Field Programmable Gate Array (FPGA)

PubMed Central

Benrekia, Fayçal; Attari, Mokhtar; Bouhedda, Mounir

2013-01-01

This paper develops a primitive gas recognition system for discriminating between industrial gas species. The system under investigation consists of an array of eight micro-hotplate-based SnO2 thin film gas sensors with different selectivity patterns. The output signals are processed through a signal conditioning and analyzing system. These signals feed a decision-making classifier, which is obtained via a Field Programmable Gate Array (FPGA) with Very High-Speed Integrated Circuit Hardware Description Language. The classifier relies on a multilayer neural network based on a back propagation algorithm with one hidden layer of four neurons and eight neurons at the input and five neurons at the output. The neural network designed after implementation consists of twenty thousand gates. The achieved experimental results seem to show the effectiveness of the proposed classifier, which can discriminate between five industrial gases. PMID:23529119

Protein recognition by a pattern-generating fluorescent molecular probe

NASA Astrophysics Data System (ADS)

Pode, Zohar; Peri-Naor, Ronny; Georgeson, Joseph M.; Ilani, Tal; Kiss, Vladimir; Unger, Tamar; Markus, Barak; Barr, Haim M.; Motiei, Leila; Margulies, David

2017-12-01

Fluorescent molecular probes have become valuable tools in protein research; however, the current methods for using these probes are less suitable for analysing specific populations of proteins in their native environment. In this study, we address this gap by developing a unimolecular fluorescent probe that combines the properties of small-molecule-based probes and cross-reactive sensor arrays (the so-called chemical 'noses/tongues'). On the one hand, the probe can detect different proteins by generating unique identification (ID) patterns, akin to cross-reactive arrays. On the other hand, its unimolecular scaffold and selective binding enable this ID-generating probe to identify combinations of specific protein families within complex mixtures and to discriminate among isoforms in living cells, where macroscopic arrays cannot access. The ability to recycle the molecular device and use it to track several binding interactions simultaneously further demonstrates how this approach could expand the fluorescent toolbox currently used to detect and image proteins.

GPU-based real-time trinocular stereo vision

NASA Astrophysics Data System (ADS)

Yao, Yuanbin; Linton, R. J.; Padir, Taskin

2013-01-01

Most stereovision applications are binocular which uses information from a 2-camera array to perform stereo matching and compute the depth image. Trinocular stereovision with a 3-camera array has been proved to provide higher accuracy in stereo matching which could benefit applications like distance finding, object recognition, and detection. This paper presents a real-time stereovision algorithm implemented on a GPGPU (General-purpose graphics processing unit) using a trinocular stereovision camera array. Algorithm employs a winner-take-all method applied to perform fusion of disparities in different directions following various image processing techniques to obtain the depth information. The goal of the algorithm is to achieve real-time processing speed with the help of a GPGPU involving the use of Open Source Computer Vision Library (OpenCV) in C++ and NVidia CUDA GPGPU Solution. The results are compared in accuracy and speed to verify the improvement.

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

PubMed

Müller-Molina, Arnoldo J; Schöler, Hans R; Araúzo-Bravo, Marcos J

2012-01-01

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.

Comprehensive Human Transcription Factor Binding Site Map for Combinatory Binding Motifs Discovery

PubMed Central

Müller-Molina, Arnoldo J.; Schöler, Hans R.; Araúzo-Bravo, Marcos J.

2012-01-01

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. PMID:23209563

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

NASA Technical Reports Server (NTRS)

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.

Programmable Self-Assembly of DNA-Dendrimer and DNA-Fullerene Nanostructures

DTIC Science & Technology

2004-10-01

separated by high pressure liquid chromatography ( HPLC ). The resulting material was analytically pure (99%) and monodisperse. Hybridization...bacterial and viral recognition, and gene expression analysis . These major accomplishments have been disseminated by various applications including 16...designing DNA strands with specific structural properties. The direct analysis of genomic DNA and RNA in an array format without labeling or

Working Memory Inefficiency: Minimal Information Is Utilized in Visual Recognition Tasks

ERIC Educational Resources Information Center

Chen, Zhijian; Cowan, Nelson

2013-01-01

Can people make perfect use of task-relevant information in working memory (WM)? Specifically, when questioned about an item in an array that does not happen to be in WM, can participants take into account other items that are in WM, eliminating them as response candidates? To address this question, an ideal-responder model that assumes perfect…

The design of RFID convey or belt gate systems using an antenna control unit.

PubMed

Park, Chong Ryol; Lee, Seung Joon; Eom, Ki Hwan

2011-01-01

This paper proposes an efficient management system utilizing a Radio Frequency Identification (RFID) antenna control unit which is moving along with the path of boxes of materials on the conveyor belt by manipulating a motor. The proposed antenna control unit, which is driven by a motor and is located on top of the gate, has an array structure of two antennas with parallel connection. The array structure helps improve the directivity of antenna beam pattern and the readable RFID distance due to its configuration. In the experiments, as the control unit follows moving materials, the reading time has been improved by almost three-fold compared to an RFID system employing conventional fixed antennas. The proposed system also has a recognition rate of over 99% without additional antennas for detecting the sides of a box of materials. The recognition rate meets the conditions recommended by the Electronic Product Code glbal network (EPC)global for commercializing the system, with three antennas at a 20 dBm power of reader and a conveyor belt speed of 3.17 m/s. This will enable a host of new RFID conveyor belt gate systems with increased performance.

Magnetic thin-film insulator with ultra-low spin wave damping for coherent nanomagnonics

NASA Astrophysics Data System (ADS)

Yu, Haiming; Kelly, O. D'allivy; Cros, V.; Bernard, R.; Bortolotti, P.; Anane, A.; Brandl, F.; Huber, R.; Stasinopoulos, I.; Grundler, D.

2014-10-01

Wave control in the solid state has opened new avenues in modern information technology. Surface-acoustic-wave-based devices are found as mass market products in 100 millions of cellular phones. Spin waves (magnons) would offer a boost in today's data handling and security implementations, i.e., image processing and speech recognition. However, nanomagnonic devices realized so far suffer from the relatively short damping length in the metallic ferromagnets amounting to a few 10 micrometers typically. Here we demonstrate that nm-thick YIG films overcome the damping chasm. Using a conventional coplanar waveguide we excite a large series of short-wavelength spin waves (SWs). From the data we estimate a macroscopic of damping length of about 600 micrometers. The intrinsic damping parameter suggests even a record value about 1 mm allowing for magnonics-based nanotechnology with ultra-low damping. In addition, SWs at large wave vector are found to exhibit the non-reciprocal properties relevant for new concepts in nanoscale SW-based logics. We expect our results to provide the basis for coherent data processing with SWs at GHz rates and in large arrays of cellular magnetic arrays, thereby boosting the envisioned image processing and speech recognition.

The Design of RFID Convey or Belt Gate Systems Using an Antenna Control Unit

PubMed Central

Park, Chong Ryol; Lee, Seung Joon; Eom, Ki Hwan

2011-01-01

This paper proposes an efficient management system utilizing a Radio Frequency Identification (RFID) antenna control unit which is moving along with the path of boxes of materials on the conveyor belt by manipulating a motor. The proposed antenna control unit, which is driven by a motor and is located on top of the gate, has an array structure of two antennas with parallel connection. The array structure helps improve the directivity of antenna beam pattern and the readable RFID distance due to its configuration. In the experiments, as the control unit follows moving materials, the reading time has been improved by almost three-fold compared to an RFID system employing conventional fixed antennas. The proposed system also has a recognition rate of over 99% without additional antennas for detecting the sides of a box of materials. The recognition rate meets the conditions recommended by the Electronic Product Code glbal network (EPC)global for commercializing the system, with three antennas at a 20 dBm power of reader and a conveyor belt speed of 3.17 m/s. This will enable a host of new RFID conveyor belt gate systems with increased performance. PMID:22164119

Magnetic thin-film insulator with ultra-low spin wave damping for coherent nanomagnonics

PubMed Central

Yu, Haiming; Kelly, O. d'Allivy; Cros, V.; Bernard, R.; Bortolotti, P.; Anane, A.; Brandl, F.; Huber, R.; Stasinopoulos, I.; Grundler, D.

2014-01-01

Wave control in the solid state has opened new avenues in modern information technology. Surface-acoustic-wave-based devices are found as mass market products in 100 millions of cellular phones. Spin waves (magnons) would offer a boost in today's data handling and security implementations, i.e., image processing and speech recognition. However, nanomagnonic devices realized so far suffer from the relatively short damping length in the metallic ferromagnets amounting to a few 10 micrometers typically. Here we demonstrate that nm-thick YIG films overcome the damping chasm. Using a conventional coplanar waveguide we excite a large series of short-wavelength spin waves (SWs). From the data we estimate a macroscopic of damping length of about 600 micrometers. The intrinsic damping parameter suggests even a record value about 1 mm allowing for magnonics-based nanotechnology with ultra-low damping. In addition, SWs at large wave vector are found to exhibit the non-reciprocal properties relevant for new concepts in nanoscale SW-based logics. We expect our results to provide the basis for coherent data processing with SWs at GHz rates and in large arrays of cellular magnetic arrays, thereby boosting the envisioned image processing and speech recognition. PMID:25355200

Formal Operations and Ego Identity in Adolescence.

ERIC Educational Resources Information Center

Wagner, Janis A.

1987-01-01

Investigated the relationship between the development of formal operations and the formation of ego identity in adolescence. Obtained significant positive correlations between combinatorial ability and degree of identity, suggesting that high identity may facilitate the application of combinatorial operations. Found some gender differences in task…

Manipulating Combinatorial Structures.

ERIC Educational Resources Information Center

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…

Gian-Carlos Rota and Combinatorial Math.

ERIC Educational Resources Information Center

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

ERIC Educational Resources Information Center

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…

The LATL as locus of composition: MEG evidence from English and Arabic.

PubMed

Westerlund, Masha; Kastner, Itamar; Al Kaabi, Meera; Pylkkänen, Liina

2015-02-01

Neurolinguistic investigations into the processing of structured sentences as well as simple adjective-noun phrases point to the left anterior temporal lobe (LATL) as a leading candidate for basic linguistic composition. Here, we characterized the combinatory profile of the LATL over a variety of syntactic and semantic environments, and across two languages, English and Arabic. The contribution of the LATL was investigated across two types of composition: the optional modification of a predicate (modification) and the satisfaction of a predicate's argument position (argument saturation). Target words were presented during MEG recordings, either in combinatory contexts (e.g. "eats meat") or in non-combinatory contexts (preceded by an unpronounceable consonant string, e.g. "xqkr meat"). Across both languages, the LATL showed increased responses to words in combinatory contexts, an effect that was robust to composition type and word order. Together with related findings, these results solidify the role of the LATL in basic semantic composition. Copyright © 2014 Elsevier Inc. All rights reserved.

DNA Assembly Techniques for Next Generation Combinatorial Biosynthesis of Natural Products

PubMed Central

Cobb, Ryan E.; Ning, Jonathan C.; Zhao, Huimin

2013-01-01

Natural product scaffolds remain important leads for pharmaceutical development. However, transforming a natural product into a drug entity often requires derivatization to enhance the compound’s therapeutic properties. A powerful method by which to perform this derivatization is combinatorial biosynthesis, the manipulation of the genes in the corresponding pathway to divert synthesis towards novel derivatives. While these manipulations have traditionally been carried out via restriction digestion/ligation-based cloning, the shortcomings of such techniques limit their throughput and thus the scope of corresponding combinatorial biosynthesis experiments. In the burgeoning field of synthetic biology, the demand for facile DNA assembly techniques has promoted the development of a host of novel DNA assembly strategies. Here we describe the advantages of these recently-developed tools for rapid, efficient synthesis of large DNA constructs. We also discuss their potential to facilitate the simultaneous assembly of complete libraries of natural product biosynthetic pathways, ushering in the next generation of combinatorial biosynthesis. PMID:24127070

Novel Design Strategy for Checkpoint Kinase 2 Inhibitors Using Pharmacophore Modeling, Combinatorial Fusion, and Virtual Screening

PubMed Central

Wang, Yen-Ling

2014-01-01

Checkpoint kinase 2 (Chk2) has a great effect on DNA-damage and plays an important role in response to DNA double-strand breaks and related lesions. In this study, we will concentrate on Chk2 and the purpose is to find the potential inhibitors by the pharmacophore hypotheses (PhModels), combinatorial fusion, and virtual screening techniques. Applying combinatorial fusion into PhModels and virtual screening techniques is a novel design strategy for drug design. We used combinatorial fusion to analyze the prediction results and then obtained the best correlation coefficient of the testing set (r test) with the value 0.816 by combining the BesttrainBesttest and FasttrainFasttest prediction results. The potential inhibitors were selected from NCI database by screening according to BesttrainBesttest + FasttrainFasttest prediction results and molecular docking with CDOCKER docking program. Finally, the selected compounds have high interaction energy between a ligand and a receptor. Through these approaches, 23 potential inhibitors for Chk2 are retrieved for further study. PMID:24864236

A methodology to find the elementary landscape decomposition of combinatorial optimization problems.

PubMed

Chicano, Francisco; Whitley, L Darrell; Alba, Enrique

2011-01-01

A small number of combinatorial optimization problems have search spaces that correspond to elementary landscapes, where the objective function f is an eigenfunction of the Laplacian that describes the neighborhood structure of the search space. Many problems are not elementary; however, the objective function of a combinatorial optimization problem can always be expressed as a superposition of multiple elementary landscapes if the underlying neighborhood used is symmetric. This paper presents theoretical results that provide the foundation for algebraic methods that can be used to decompose the objective function of an arbitrary combinatorial optimization problem into a sum of subfunctions, where each subfunction is an elementary landscape. Many steps of this process can be automated, and indeed a software tool could be developed that assists the researcher in finding a landscape decomposition. This methodology is then used to show that the subset sum problem is a superposition of two elementary landscapes, and to show that the quadratic assignment problem is a superposition of three elementary landscapes.

A Metagenome-Wide Association Study and Arrayed Mutant Library Confirm Acetobacter Lipopolysaccharide Genes Are Necessary for Association with Drosophila melanogaster.

PubMed

White, K Makay; Matthews, Melinda K; Hughes, Rachel C; Sommer, Andrew J; Griffitts, Joel S; Newell, Peter D; Chaston, John M

2018-03-28

A metagenome wide association (MGWA) study of bacterial host association determinants in Drosophila predicted that LPS biosynthesis genes are significantly associated with host colonization. We were unable to create site-directed mutants for each of the predicted genes in Acetobacter , so we created an arrayed transposon insertion library using Acetobacter fabarum DsW_054 isolated from Drosophila Creation of the A. fabarum DsW_054 gene knock-out library was performed by combinatorial mapping and Illumina sequencing of random transposon insertion mutants. Transposon insertion locations for 6,418 mutants were successfully mapped, including hits within 63% of annotated genes in the A. fabarum DsW_054 genome. For 45/45 members of the library, insertion sites were verified by arbitrary PCR and Sanger sequencing. Mutants with insertions in four different LPS biosynthesis genes were selected from the library to validate the MGWA predictions. Insertion mutations in two genes biosynthetically upstream of Lipid-A formation, lpxC and lpxB , show significant differences in host association, whereas mutations in two genes encoding LPS biosynthesis functions downstream of Lipid-A biosynthesis had no effect. These results suggest an impact of bacterial cell surface molecules on the bacterial capacity for host association. Also, the transposon insertion mutant library will be a useful resource for ongoing research on the genetic basis for Acetobacter traits. Copyright © 2018 White et al.

Two forms of persistence in visual information processing.

PubMed

Di Lollo, Vincent; Dixon, Peter

1988-11-01

Iconic memory, which was initially regarded as a unitary phenomenon, has since been subdivided into several components. In the present work we examined the joint effects of two such components (visible persistence and the visual analog representation) on performance in a partial report task. The display consisted of 15 alphabetic characters arranged around the perimeter of an imaginary circle on the face of an oscilloscope. The observer named the character singled out by a bar-probe. Two factors were varied: exposure duration of the array (10, 50, 100, 150, 200, 300, 400 or 500 ms) and duration of blank period (interstimulus interval, ISI) between the termination of the array and the onset of the probe (0, 50, 100, 150, or 200 ms). Performance was progressively impaired as both exposure duration and ISI were increased. The results were explained in terms of a probabilistic combinatorial model in which the timecourses of visible persistence and of the visual analog representation are regarded as time-locked to the onset and to the end of stimulation, respectively. The impairing effect of exposure duration was attributed to the relatively high spatial demands of the task that could be met optimally by information in visible persistence (which declines as a function of exposure duration), but less adequately by information in the visual analog representation. A second experiment, employing a task with lesser spatial demands, confirmed this interpretation.

An evolutionary strategy based on partial imitation for solving optimization problems

NASA Astrophysics Data System (ADS)

Javarone, Marco Alberto

2016-12-01

In this work we introduce an evolutionary strategy to solve combinatorial optimization tasks, i.e. problems characterized by a discrete search space. In particular, we focus on the Traveling Salesman Problem (TSP), i.e. a famous problem whose search space grows exponentially, increasing the number of cities, up to becoming NP-hard. The solutions of the TSP can be codified by arrays of cities, and can be evaluated by fitness, computed according to a cost function (e.g. the length of a path). Our method is based on the evolution of an agent population by means of an imitative mechanism, we define 'partial imitation'. In particular, agents receive a random solution and then, interacting among themselves, may imitate the solutions of agents with a higher fitness. Since the imitation mechanism is only partial, agents copy only one entry (randomly chosen) of another array (i.e. solution). In doing so, the population converges towards a shared solution, behaving like a spin system undergoing a cooling process, i.e. driven towards an ordered phase. We highlight that the adopted 'partial imitation' mechanism allows the population to generate solutions over time, before reaching the final equilibrium. Results of numerical simulations show that our method is able to find, in a finite time, both optimal and suboptimal solutions, depending on the size of the considered search space.

Solution NMR studies provide structural basis for endotoxin pattern recognition by the innate immune receptor CD14

DOE Office of Scientific and Technical Information (OSTI.GOV)

Albright, Seth; Chen Bin; Holbrook, Kristen

CD14 functions as a key pattern recognition receptor for a diverse array of Gram-negative and Gram-positive cell-wall components in the host innate immune response by binding to pathogen-associated molecular patterns (PAMPs) at partially overlapping binding site(s). To determine the potential contribution of CD14 residues in this pattern recognition, we have examined using solution NMR spectroscopy, the binding of three different endotoxin ligands, lipopolysaccharide, lipoteichoic acid, and a PGN-derived compound, muramyl dipeptide to a {sup 15}N isotopically labeled 152-residue N-terminal fragment of sCD14 expressed in Pichia pastoris. Mapping of NMR spectral changes upon addition of ligands revealed that the pattern ofmore » residues affected by binding of each ligand is partially similar and partially different. This first direct structural observation of the ability of specific residue combinations of CD14 to differentially affect endotoxin binding may help explain the broad specificity of CD14 in ligand recognition and provide a structural basis for pattern recognition. Another interesting finding from the observed spectral changes is that the mode of binding may be dynamically modulated and could provide a mechanism for binding endotoxins with structural diversity through a common binding site.« less

A miniature electronic nose system based on an MWNT-polymer microsensor array and a low-power signal-processing chip.

PubMed

Chiu, Shih-Wen; Wu, Hsiang-Chiu; Chou, Ting-I; Chen, Hsin; Tang, Kea-Tiong

2014-06-01

This article introduces a power-efficient, miniature electronic nose (e-nose) system. The e-nose system primarily comprises two self-developed chips, a multiple-walled carbon nanotube (MWNT)-polymer based microsensor array, and a low-power signal-processing chip. The microsensor array was fabricated on a silicon wafer by using standard photolithography technology. The microsensor array comprised eight interdigitated electrodes surrounded by SU-8 "walls," which restrained the material-solvent liquid in a defined area of 650 × 760 μm(2). To achieve a reliable sensor-manufacturing process, we used a two-layer deposition method, coating the MWNTs and polymer film as the first and second layers, respectively. The low-power signal-processing chip included array data acquisition circuits and a signal-processing core. The MWNT-polymer microsensor array can directly connect with array data acquisition circuits, which comprise sensor interface circuitry and an analog-to-digital converter; the signal-processing core consists of memory and a microprocessor. The core executes the program, classifying the odor data received from the array data acquisition circuits. The low-power signal-processing chip was designed and fabricated using the Taiwan Semiconductor Manufacturing Company 0.18-μm 1P6M standard complementary metal oxide semiconductor process. The chip consumes only 1.05 mW of power at supply voltages of 1 and 1.8 V for the array data acquisition circuits and the signal-processing core, respectively. The miniature e-nose system, which used a microsensor array, a low-power signal-processing chip, and an embedded k-nearest-neighbor-based pattern recognition algorithm, was developed as a prototype that successfully recognized the complex odors of tincture, sorghum wine, sake, whisky, and vodka.

In vitro and direct in vivo testing of mixture-based combinatorial libraries for the identification of highly active and specific opiate ligands.

PubMed

Houghten, Richard A; Dooley, Colette T; Appel, Jon R

2006-05-26

The use of combinatorial libraries for the identification of novel opiate and related ligands in opioid receptor assays is reviewed. Case studies involving opioid assays used to demonstrate the viability of combinatorial libraries are described. The identification of new opioid peptides composed of L-amino acids, D-amino acids, or L-, D-, and unnatural amino acids is reviewed. New opioid compounds have also been identified from peptidomimetic libraries, such as peptoids and alkylated dipeptides, and those identified from acyclic (eg, polyamine, urea) and heterocyclic (eg, bicyclic guanidine) libraries are reviewed.

Prototype Focal-Plane-Array Optoelectronic Image Processor

NASA Technical Reports Server (NTRS)

Fang, Wai-Chi; Shaw, Timothy; Yu, Jeffrey

1995-01-01

Prototype very-large-scale integrated (VLSI) planar array of optoelectronic processing elements combines speed of optical input and output with flexibility of reconfiguration (programmability) of electronic processing medium. Basic concept of processor described in "Optical-Input, Optical-Output Morphological Processor" (NPO-18174). Performs binary operations on binary (black and white) images. Each processing element corresponds to one picture element of image and located at that picture element. Includes input-plane photodetector in form of parasitic phototransistor part of processing circuit. Output of each processing circuit used to modulate one picture element in output-plane liquid-crystal display device. Intended to implement morphological processing algorithms that transform image into set of features suitable for high-level processing; e.g., recognition.

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

ERIC Educational Resources Information Center

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'…

Memristor-Based Analog Computation and Neural Network Classification with a Dot Product Engine.

PubMed

Hu, Miao; Graves, Catherine E; Li, Can; Li, Yunning; Ge, Ning; Montgomery, Eric; Davila, Noraica; Jiang, Hao; Williams, R Stanley; Yang, J Joshua; Xia, Qiangfei; Strachan, John Paul

2018-03-01

Using memristor crossbar arrays to accelerate computations is a promising approach to efficiently implement algorithms in deep neural networks. Early demonstrations, however, are limited to simulations or small-scale problems primarily due to materials and device challenges that limit the size of the memristor crossbar arrays that can be reliably programmed to stable and analog values, which is the focus of the current work. High-precision analog tuning and control of memristor cells across a 128 × 64 array is demonstrated, and the resulting vector matrix multiplication (VMM) computing precision is evaluated. Single-layer neural network inference is performed in these arrays, and the performance compared to a digital approach is assessed. Memristor computing system used here reaches a VMM accuracy equivalent of 6 bits, and an 89.9% recognition accuracy is achieved for the 10k MNIST handwritten digit test set. Forecasts show that with integrated (on chip) and scaled memristors, a computational efficiency greater than 100 trillion operations per second per Watt is possible. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Redesigning photo-ID to improve unfamiliar face matching performance.

PubMed

White, David; Burton, A Mike; Jenkins, Rob; Kemp, Richard I

2014-06-01

Viewers find it difficult to match photos of unfamiliar faces for identity. Despite this, the use of photographic ID is widespread. In this study we ask whether it is possible to improve face matching performance by replacing single photographs on ID documents with multiple photos or an average image of the bearer. In 3 experiments we compare photo-to-photo matching with photo-to-average matching (where the average is formed from multiple photos of the same person) and photo-to-array matching (where the array comprises separate photos of the same person). We consistently find an accuracy advantage for average images and photo arrays over single photos, and show that this improvement is driven by performance in match trials. In the final experiment, we find a benefit of 4-image arrays relative to average images for unfamiliar faces, but not for familiar faces. We propose that conventional photo-ID format can be improved, and discuss this finding in the context of face recognition more generally. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Quantum Efficiency and Bandgap Analysis for Combinatorial Photovoltaics: Sorting Activity of Cu–O Compounds in All-Oxide Device Libraries

PubMed Central

2014-01-01

All-oxide-based photovoltaics (PVs) encompass the potential for extremely low cost solar cells, provided they can obtain an order of magnitude improvement in their power conversion efficiencies. To achieve this goal, we perform a combinatorial materials study of metal oxide based light absorbers, charge transporters, junctions between them, and PV devices. Here we report the development of a combinatorial internal quantum efficiency (IQE) method. IQE measures the efficiency associated with the charge separation and collection processes, and thus is a proxy for PV activity of materials once placed into devices, discarding optical properties that cause uncontrolled light harvesting. The IQE is supported by high-throughput techniques for bandgap fitting, composition analysis, and thickness mapping, which are also crucial parameters for the combinatorial investigation cycle of photovoltaics. As a model system we use a library of 169 solar cells with a varying thickness of sprayed titanium dioxide (TiO2) as the window layer, and covarying thickness and composition of binary compounds of copper oxides (Cu–O) as the light absorber, fabricated by Pulsed Laser Deposition (PLD). The analysis on the combinatorial devices shows the correlation between compositions and bandgap, and their effect on PV activity within several device configurations. The analysis suggests that the presence of Cu4O3 plays a significant role in the PV activity of binary Cu–O compounds. PMID:24410367

Molecular biomimetics: utilizing nature's molecular ways in practical engineering.

PubMed

Tamerler, Candan; Sarikaya, Mehmet

2007-05-01

In nature, proteins are the machinery that accomplish many functions through their specific recognition and interactions in biological systems from single-celled to multicellular organisms. Biomolecule-material interaction is accomplished via molecular specificity, leading to the formation of controlled structures and functions at all scales of dimensional hierarchy. Through evolution, molecular recognition and, consequently, functions developed through successive cycles of mutation and selection. Using biology as a guide, we can now understand, engineer and control peptide-material interactions and exploit these to tailor novel materials and systems for practical applications. We adapted combinatorial biology protocols to display peptide libraries, either on the cell surface or on phages, to select short peptides specific to a variety of practical materials systems. Following the selection step, we determined the kinetics and stability of peptide binding experimentally to understand the bound peptide structure via modeling and its assembly via atomic force microscopy. The peptides were further engineered to have multiple repeats or their amino acid sequences varied to tailor their function. Both nanoparticles and flat inorganic substrates containing multimaterials patterned at the nano- and microscales were used for self-directed immobilization of molecular constructs. The molecular biomimetic approach opens up new avenues for the design and utilization of multifunctional molecular systems with wide ranging applications, from tissue engineering, drug delivery and biosensors, to nanotechnology and bioremediation. Here we give examples of protein-mediated functional materials in biology, peptide selection and engineering with affinity to inorganics, demonstrate potential utilizations in materials science, engineering and medicine, and describe future prospects.

Whole-face procedures for recovering facial images from memory.

PubMed

Frowd, Charlie D; Skelton, Faye; Hepton, Gemma; Holden, Laura; Minahil, Simra; Pitchford, Melanie; McIntyre, Alex; Brown, Charity; Hancock, Peter J B

2013-06-01

Research has indicated that traditional methods for accessing facial memories usually yield unidentifiable images. Recent research, however, has made important improvements in this area to the witness interview, method used for constructing the face and recognition of finished composites. Here, we investigated whether three of these improvements would produce even-more recognisable images when used in conjunction with each other. The techniques are holistic in nature: they involve processes which operate on an entire face. Forty participants first inspected an unfamiliar target face. Nominally 24h later, they were interviewed using a standard type of cognitive interview (CI) to recall the appearance of the target, or an enhanced 'holistic' interview where the CI was followed by procedures for focussing on the target's character. Participants then constructed a composite using EvoFIT, a recognition-type system that requires repeatedly selecting items from face arrays, with 'breeding', to 'evolve' a composite. They either saw faces in these arrays with blurred external features, or an enhanced method where these faces were presented with masked external features. Then, further participants attempted to name the composites, first by looking at the face front-on, the normal method, and then for a second time by looking at the face side-on, which research demonstrates facilitates recognition. All techniques improved correct naming on their own, but together promoted highly-recognisable composites with mean naming at 74% correct. The implication is that these techniques, if used together by practitioners, should substantially increase the detection of suspects using this forensic method of person identification. Copyright © 2013 Forensic Science Society. Published by Elsevier Ireland Ltd. All rights reserved.

Effectiveness of the Directional Microphone in the Baha® Divino™

PubMed Central

Oeding, Kristi; Valente, Michael; Kerckhoff, Jessica

2010-01-01

Background Patients with unilateral sensorineural hearing loss (USNHL) experience great difficulty listening to speech in noisy environments. A directional microphone (DM) could potentially improve speech recognition in this difficult listening environment. It is well known that DMs in behind-the-ear (BTE) and custom hearing aids can provide a greater signal-to-noise ratio (SNR) in comparison to an omnidirectional microphone (OM) to improve speech recognition in noise for persons with hearing impairment. Studies examining the DM in bone anchored auditory osseointegrated implants (Baha), however, have been mixed, with little to no benefit reported for the DM compared to an OM. Purpose The primary purpose of this study was to determine if there are statistically significant differences in the mean reception threshold for sentences (RTS in dB) in noise between the OM and DM in the Baha® Divino™. The RTS of these two microphone modes was measured utilizing two loudspeaker arrays (speech from 0° and noise from 180° or a diffuse eight-loudspeaker array) and with the better ear open or closed with an earmold impression and noise attenuating earmuff. Subjective benefit was assessed using the Abbreviated Profile of Hearing Aid Benefit (APHAB) to compare unaided and aided (Divino OM and DM combined) problem scores. Research Design A repeated measures design was utilized, with each subject counterbalanced to each of the eight treatment levels for three independent variables: (1) microphone (OM and DM), (2) loudspeaker array (180° and diffuse), and (3) better ear (open and closed). Study Sample Sixteen subjects with USNHL currently utilizing the Baha were recruited from Washington University’s Center for Advanced Medicine and the surrounding area. Data Collection and Analysis Subjects were tested at the initial visit if they entered the study wearing the Divino or after at least four weeks of acclimatization to a loaner Divino. The RTS was determined utilizing Hearing in Noise Test (HINT) sentences in the R-Space™ system, and subjective benefit was determined utilizing the APHAB. A three-way repeated measures analysis of variance (ANOVA) and a paired samples t-test were utilized to analyze results of the HINT and APHAB, respectively. Results Results revealed statistically significant differences within microphone (p < 0.001; directional advantage of 3.2 dB), loudspeaker array (p = 0.046; 180° advantage of 1.1 dB), and better ear conditions (p < 0.001; open ear advantage of 4.9 dB). Results from the APHAB revealed statistically and clinically significant benefit for the Divino relative to unaided on the subscales of Ease of Communication (EC) (p = 0.037), Background Noise (BN) (p < 0.001), and Reverberation (RV) (p = 0.005). Conclusions The Divino’s DM provides a statistically significant improvement in speech recognition in noise compared to the OM for subjects with USNHL. Therefore, it is recommended that audiologists consider selecting a Baha with a DM to provide improved speech recognition performance in noisy listening environments. PMID:21034701

Effectiveness of the directional microphone in the Baha® Divino™.

PubMed

Oeding, Kristi; Valente, Michael; Kerckhoff, Jessica

2010-09-01

Patients with unilateral sensorineural hearing loss (USNHL) experience great difficulty listening to speech in noisy environments. A directional microphone (DM) could potentially improve speech recognition in this difficult listening environment. It is well known that DMs in behind-the-ear (BTE) and custom hearing aids can provide a greater signal-to-noise ratio (SNR) in comparison to an omnidirectional microphone (OM) to improve speech recognition in noise for persons with hearing impairment. Studies examining the DM in bone anchored auditory osseointegrated implants (Baha), however, have been mixed, with little to no benefit reported for the DM compared to an OM. The primary purpose of this study was to determine if there are statistically significant differences in the mean reception threshold for sentences (RTS in dB) in noise between the OM and DM in the Baha® Divino™. The RTS of these two microphone modes was measured utilizing two loudspeaker arrays (speech from 0° and noise from 180° or a diffuse eight-loudspeaker array) and with the better ear open or closed with an earmold impression and noise attenuating earmuff. Subjective benefit was assessed using the Abbreviated Profile of Hearing Aid Benefit (APHAB) to compare unaided and aided (Divino OM and DM combined) problem scores. A repeated measures design was utilized, with each subject counterbalanced to each of the eight treatment levels for three independent variables: (1) microphone (OM and DM), (2) loudspeaker array (180° and diffuse), and (3) better ear (open and closed). Sixteen subjects with USNHL currently utilizing the Baha were recruited from Washington University's Center for Advanced Medicine and the surrounding area. Subjects were tested at the initial visit if they entered the study wearing the Divino or after at least four weeks of acclimatization to a loaner Divino. The RTS was determined utilizing Hearing in Noise Test (HINT) sentences in the R-Space™ system, and subjective benefit was determined utilizing the APHAB. A three-way repeated measures analysis of variance (ANOVA) and a paired samples t-test were utilized to analyze results of the HINT and APHAB, respectively. Results revealed statistically significant differences within microphone (p < 0.001; directional advantage of 3.2 dB), loudspeaker array (p = 0.046; 180° advantage of 1.1 dB), and better ear conditions (p < 0.001; open ear advantage of 4.9 dB). Results from the APHAB revealed statistically and clinically significant benefit for the Divino relative to unaided on the subscales of Ease of Communication (EC) (p = 0.037), Background Noise (BN) (p < 0.001), and Reverberation (RV) (p = 0.005). The Divino's DM provides a statistically significant improvement in speech recognition in noise compared to the OM for subjects with USNHL. Therefore, it is recommended that audiologists consider selecting a Baha with a DM to provide improved speech recognition performance in noisy listening environments. American Academy of Audiology.

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

USDA-ARS?s Scientific Manuscript database

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...

Students' Verification Strategies for Combinatorial Problems

ERIC Educational Resources Information Center

Mashiach Eizenberg, Michal; Zaslavsky, Orit

2004-01-01

We focus on a major difficulty in solving combinatorial problems, namely, on the verification of a solution. Our study aimed at identifying undergraduate students' tendencies to verify their solutions, and the verification strategies that they employ when solving these problems. In addition, an attempt was made to evaluate the level of efficiency…

Modeling guidance and recognition in categorical search: bridging human and computer object detection.

PubMed

Zelinsky, Gregory J; Peng, Yifan; Berg, Alexander C; Samaras, Dimitris

2013-10-08

Search is commonly described as a repeating cycle of guidance to target-like objects, followed by the recognition of these objects as targets or distractors. Are these indeed separate processes using different visual features? We addressed this question by comparing observer behavior to that of support vector machine (SVM) models trained on guidance and recognition tasks. Observers searched for a categorically defined teddy bear target in four-object arrays. Target-absent trials consisted of random category distractors rated in their visual similarity to teddy bears. Guidance, quantified as first-fixated objects during search, was strongest for targets, followed by target-similar, medium-similarity, and target-dissimilar distractors. False positive errors to first-fixated distractors also decreased with increasing dissimilarity to the target category. To model guidance, nine teddy bear detectors, using features ranging in biological plausibility, were trained on unblurred bears then tested on blurred versions of the same objects appearing in each search display. Guidance estimates were based on target probabilities obtained from these detectors. To model recognition, nine bear/nonbear classifiers, trained and tested on unblurred objects, were used to classify the object that would be fixated first (based on the detector estimates) as a teddy bear or a distractor. Patterns of categorical guidance and recognition accuracy were modeled almost perfectly by an HMAX model in combination with a color histogram feature. We conclude that guidance and recognition in the context of search are not separate processes mediated by different features, and that what the literature knows as guidance is really recognition performed on blurred objects viewed in the visual periphery.

Modeling guidance and recognition in categorical search: Bridging human and computer object detection

PubMed Central

Zelinsky, Gregory J.; Peng, Yifan; Berg, Alexander C.; Samaras, Dimitris

2013-01-01

Search is commonly described as a repeating cycle of guidance to target-like objects, followed by the recognition of these objects as targets or distractors. Are these indeed separate processes using different visual features? We addressed this question by comparing observer behavior to that of support vector machine (SVM) models trained on guidance and recognition tasks. Observers searched for a categorically defined teddy bear target in four-object arrays. Target-absent trials consisted of random category distractors rated in their visual similarity to teddy bears. Guidance, quantified as first-fixated objects during search, was strongest for targets, followed by target-similar, medium-similarity, and target-dissimilar distractors. False positive errors to first-fixated distractors also decreased with increasing dissimilarity to the target category. To model guidance, nine teddy bear detectors, using features ranging in biological plausibility, were trained on unblurred bears then tested on blurred versions of the same objects appearing in each search display. Guidance estimates were based on target probabilities obtained from these detectors. To model recognition, nine bear/nonbear classifiers, trained and tested on unblurred objects, were used to classify the object that would be fixated first (based on the detector estimates) as a teddy bear or a distractor. Patterns of categorical guidance and recognition accuracy were modeled almost perfectly by an HMAX model in combination with a color histogram feature. We conclude that guidance and recognition in the context of search are not separate processes mediated by different features, and that what the literature knows as guidance is really recognition performed on blurred objects viewed in the visual periphery. PMID:24105460

The structure and dynamics of tandem WW domains in a negative regulator of notch signaling, Suppressor of deltex.

PubMed

Fedoroff, Oleg Y; Townson, Sharon A; Golovanov, Alexander P; Baron, Martin; Avis, Johanna M

2004-08-13

WW domains mediate protein recognition, usually though binding to proline-rich sequences. In many proteins, WW domains occur in tandem arrays. Whether or how individual domains within such arrays cooperate to recognize biological partners is, as yet, poorly characterized. An important question is whether functional diversity of different WW domain proteins is reflected in the structural organization and ligand interaction mechanisms of their multiple domains. We have determined the solution structure and dynamics of a pair of WW domains (WW3-4) from a Drosophila Nedd4 family protein called Suppressor of deltex (Su(dx)), a regulator of Notch receptor signaling. We find that the binding of a type 1 PPPY ligand to WW3 stabilizes the structure with effects propagating to the WW4 domain, a domain that is not active for ligand binding. Both WW domains adopt the characteristic triple-stranded beta-sheet structure, and significantly, this is the first example of a WW domain structure to include a domain (WW4) lacking the second conserved Trp (replaced by Phe). The domains are connected by a flexible linker, which allows a hinge-like motion of domains that may be important for the recognition of functionally relevant targets. Our results contrast markedly with those of the only previously determined three-dimensional structure of tandem WW domains, that of the rigidly oriented WW domain pair from the RNA-splicing factor Prp40. Our data illustrate that arrays of WW domains can exhibit a variety of higher order structures and ligand interaction mechanisms.

In situ fabrication of cleavable peptide arrays on polydimethylsiloxane and applications for kinase activity assays.

PubMed

Chen, Huang-Han; Hsiao, Yu-Chieh; Li, Jie-Ren; Chen, Shu-Hui

2015-03-20

Polydimethylsiloxane (PDMS) is widely used for microfabrication and bioanalysis; however, its surface functionalization is limited due to the lack of active functional groups and incompatibility with many solvents. We presented a novel approach for in situ fabrication of cleavable peptide arrays on polydimethylsiloxane (PDMS) viatert-butyloxycarbonyl (t-Boc)/trifluoroacetic acid (TFA) chemistry using gold nanoparticles (AuNPs) as the anchor and a disulfide/amine terminated hetero-polyethylene glycol as the cleavable linker. The method was fine tuned to use reagents compatible with the PDMS. Using 5-mer pentapeptide, Trp5, as a model, step-by-step covalent coupling during the reaction cycles was monitored by Attenuated total reflectance-Fourier transform infrared spectrometer (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), or atomic force microscopy (AFM), and further confirmed by mass spectrometry (MS) detection of the cleaved peptides. Using such a method, heptapeptides of the PKA substrate, LRRASLG (Kemptide), and its point mutated analogs were fabricated in an array format for comparative studies of cAMP-dependent protein kinase (PKA) activity. Based on on-chip detection, Kemptide sequence exhibited the highest phosphorylation activity, which was detected to a 1.5-time lesser extent for the point mutated sequence (LRRGSLG) containing the recognition motif (RRXS), and was nearly undetectable for another point mutated sequence (LRLASLG) that lacked the recognition motif. These results indicate that the reported fabrication method is able to yield highly specific peptide sequences on PDMS, leading to a highly motif-sensitive enzyme activity assay. Copyright © 2015 Elsevier B.V. All rights reserved.

Modular Analytical Multicomponent Analysis in Gas Sensor Aarrays

PubMed Central

Chaiyboun, Ali; Traute, Rüdiger; Kiesewetter, Olaf; Ahlers, Simon; Müller, Gerhard; Doll, Theodor

2006-01-01

A multi-sensor system is a chemical sensor system which quantitatively and qualitatively records gases with a combination of cross-sensitive gas sensor arrays and pattern recognition software. This paper addresses the issue of data analysis for identification of gases in a gas sensor array. We introduce a software tool for gas sensor array configuration and simulation. It concerns thereby about a modular software package for the acquisition of data of different sensors. A signal evaluation algorithm referred to as matrix method was used specifically for the software tool. This matrix method computes the gas concentrations from the signals of a sensor array. The software tool was used for the simulation of an array of five sensors to determine gas concentration of CH4, NH3, H2, CO and C2H5OH. The results of the present simulated sensor array indicate that the software tool is capable of the following: (a) identify a gas independently of its concentration; (b) estimate the concentration of the gas, even if the system was not previously exposed to this concentration; (c) tell when a gas concentration exceeds a certain value. A gas sensor data base was build for the configuration of the software. With the data base one can create, generate and manage scenarios and source files for the simulation. With the gas sensor data base and the simulation software an on-line Web-based version was developed, with which the user can configure and simulate sensor arrays on-line.

Diversity of Prdm9 Zinc Finger Array in Wild Mice Unravels New Facets of the Evolutionary Turnover of this Coding Minisatellite

PubMed Central

Buard, Jérôme; Rivals, Eric; Dunoyer de Segonzac, Denis; Garres, Charlotte; Caminade, Pierre; de Massy, Bernard; Boursot, Pierre

2014-01-01

In humans and mice, meiotic recombination events cluster into narrow hotspots whose genomic positions are defined by the PRDM9 protein via its DNA binding domain constituted of an array of zinc fingers (ZnFs). High polymorphism and rapid divergence of the Prdm9 gene ZnF domain appear to involve positive selection at DNA-recognition amino-acid positions, but the nature of the underlying evolutionary pressures remains a puzzle. Here we explore the variability of the Prdm9 ZnF array in wild mice, and uncovered a high allelic diversity of both ZnF copy number and identity with the caracterization of 113 alleles. We analyze features of the diversity of ZnF identity which is mostly due to non-synonymous changes at codons −1, 3 and 6 of each ZnF, corresponding to amino-acids involved in DNA binding. Using methods adapted to the minisatellite structure of the ZnF array, we infer a phylogenetic tree of these alleles. We find the sister species Mus spicilegus and M. macedonicus as well as the three house mouse (Mus musculus) subspecies to be polyphyletic. However some sublineages have expanded independently in Mus musculus musculus and M. m. domesticus, the latter further showing phylogeographic substructure. Compared to random genomic regions and non-coding minisatellites, none of these patterns appears exceptional. In silico prediction of DNA binding sites for each allele, overlap of their alignments to the genome and relative coverage of the different families of interspersed repeated elements suggest a large diversity between PRDM9 variants with a potential for highly divergent distributions of recombination events in the genome with little correlation to evolutionary distance. By compiling PRDM9 ZnF protein sequences in Primates, Muridae and Equids, we find different diversity patterns among the three amino-acids most critical for the DNA-recognition function, suggesting different diversification timescales. PMID:24454780

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

PubMed

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.

Reconfigurable Gabor Filter For Fingerprint Recognition Using FPGA Verilog

NASA Astrophysics Data System (ADS)

Rosshidi, H. T.; Hadi, A. R.

2009-06-01

This paper present the implementations of Gabor filter for fingerprint recognition using Verilog HDL. This work demonstrates the application of Gabor Filter technique to enhance the fingerprint image. The incoming signal in form of image pixel will be filter out or convolute by the Gabor filter to define the ridge and valley regions of fingerprint. This is done with the application of a real time convolve based on Field Programmable Gate Array (FPGA) to perform the convolution operation. The main characteristic of the proposed approach are the usage of memory to store the incoming image pixel and the coefficient of the Gabor filter before the convolution matrix take place. The result was the signal convoluted with the Gabor coefficient.

Iris unwrapping using the Bresenham circle algorithm for real-time iris recognition

NASA Astrophysics Data System (ADS)

Carothers, Matthew T.; Ngo, Hau T.; Rakvic, Ryan N.; Broussard, Randy P.

2015-02-01

An efficient parallel architecture design for the iris unwrapping process in a real-time iris recognition system using the Bresenham Circle Algorithm is presented in this paper. Based on the characteristics of the model parameters this algorithm was chosen over the widely used polar conversion technique as the iris unwrapping model. The architecture design is parallelized to increase the throughput of the system and is suitable for processing an inputted image size of 320 × 240 pixels in real-time using Field Programmable Gate Array (FPGA) technology. Quartus software is used to implement, verify, and analyze the design's performance using the VHSIC Hardware Description Language. The system's predicted processing time is faster than the modern iris unwrapping technique used today∗.

Image processing strategies based on saliency segmentation for object recognition under simulated prosthetic vision.

PubMed

Li, Heng; Su, Xiaofan; Wang, Jing; Kan, Han; Han, Tingting; Zeng, Yajie; Chai, Xinyu

2018-01-01

Current retinal prostheses can only generate low-resolution visual percepts constituted of limited phosphenes which are elicited by an electrode array and with uncontrollable color and restricted grayscale. Under this visual perception, prosthetic recipients can just complete some simple visual tasks, but more complex tasks like face identification/object recognition are extremely difficult. Therefore, it is necessary to investigate and apply image processing strategies for optimizing the visual perception of the recipients. This study focuses on recognition of the object of interest employing simulated prosthetic vision. We used a saliency segmentation method based on a biologically plausible graph-based visual saliency model and a grabCut-based self-adaptive-iterative optimization framework to automatically extract foreground objects. Based on this, two image processing strategies, Addition of Separate Pixelization and Background Pixel Shrink, were further utilized to enhance the extracted foreground objects. i) The results showed by verification of psychophysical experiments that under simulated prosthetic vision, both strategies had marked advantages over Direct Pixelization in terms of recognition accuracy and efficiency. ii) We also found that recognition performance under two strategies was tied to the segmentation results and was affected positively by the paired-interrelated objects in the scene. The use of the saliency segmentation method and image processing strategies can automatically extract and enhance foreground objects, and significantly improve object recognition performance towards recipients implanted a high-density implant. Copyright © 2017 Elsevier B.V. All rights reserved.

Bimodal benefits on objective and subjective outcomes for adult cochlear implant users.

PubMed

Heo, Ji-Hye; Lee, Jae-Hee; Lee, Won-Sang

2013-09-01

Given that only a few studies have focused on the bimodal benefits on objective and subjective outcomes and emphasized the importance of individual data, the present study aimed to measure the bimodal benefits on the objective and subjective outcomes for adults with cochlear implant. Fourteen listeners with bimodal devices were tested on the localization and recognition abilities using environmental sounds, 1-talker, and 2-talker speech materials. The localization ability was measured through an 8-loudspeaker array. For the recognition measures, listeners were asked to repeat the sentences or say the environmental sounds the listeners heard. As a subjective questionnaire, three domains of Korean-version of Speech, Spatial, Qualities of Hearing scale (K-SSQ) were used to explore any relationships between objective and subjective outcomes. Based on the group-mean data, the bimodal hearing enhanced both localization and recognition regardless of test material. However, the inter- and intra-subject variability appeared to be large across test materials for both localization and recognition abilities. Correlation analyses revealed that the relationships were not always consistent between the objective outcomes and the subjective self-reports with bimodal devices. Overall, this study supports significant bimodal advantages on localization and recognition measures, yet the large individual variability in bimodal benefits should be considered carefully for the clinical assessment as well as counseling. The discrepant relations between objective and subjective results suggest that the bimodal benefits in traditional localization or recognition measures might not necessarily correspond to the self-reported subjective advantages in everyday listening environments.

SNPchiMp v.3: integrating and standardizing single nucleotide polymorphism data for livestock species.

PubMed

Nicolazzi, Ezequiel L; Caprera, Andrea; Nazzicari, Nelson; Cozzi, Paolo; Strozzi, Francesco; Lawley, Cindy; Pirani, Ali; Soans, Chandrasen; Brew, Fiona; Jorjani, Hossein; Evans, Gary; Simpson, Barry; Tosser-Klopp, Gwenola; Brauning, Rudiger; Williams, John L; Stella, Alessandra

2015-04-10

In recent years, the use of genomic information in livestock species for genetic improvement, association studies and many other fields has become routine. In order to accommodate different market requirements in terms of genotyping cost, manufacturers of single nucleotide polymorphism (SNP) arrays, private companies and international consortia have developed a large number of arrays with different content and different SNP density. The number of currently available SNP arrays differs among species: ranging from one for goats to more than ten for cattle, and the number of arrays available is increasing rapidly. However, there is limited or no effort to standardize and integrate array- specific (e.g. SNP IDs, allele coding) and species-specific (i.e. past and current assemblies) SNP information. Here we present SNPchiMp v.3, a solution to these issues for the six major livestock species (cow, pig, horse, sheep, goat and chicken). Original data was collected directly from SNP array producers and specific international genome consortia, and stored in a MySQL database. The database was then linked to an open-access web tool and to public databases. SNPchiMp v.3 ensures fast access to the database (retrieving within/across SNP array data) and the possibility of annotating SNP array data in a user-friendly fashion. This platform allows easy integration and standardization, and it is aimed at both industry and research. It also enables users to easily link the information available from the array producer with data in public databases, without the need of additional bioinformatics tools or pipelines. In recognition of the open-access use of Ensembl resources, SNPchiMp v.3 was officially credited as an Ensembl E!mpowered tool. Availability at http://bioinformatics.tecnoparco.org/SNPchimp.

Mining the human gut microbiota for effector strains that shape the immune system

PubMed Central

Ahern, Philip P.; Faith, Jeremiah J.; Gordon, Jeffrey I.

2014-01-01

Summary The gut microbiota co-develops with the immune system beginning at birth. Mining the microbiota for bacterial strains responsible for shaping the structure and dynamic operations of the innate and adaptive arms of the immune system represents a formidable combinatorial problem but one that needs to be overcome to advance mechanistic understanding of microbial community-immune system co-regulation, and in order to develop new diagnostic and therapeutic approaches that promote health. Here, we discuss a scalable, less biased approach for identifying effector strains in complex microbial communities that impact immune function. The approach begins by identifying uncultured human fecal microbiota samples that transmit immune phenotypes to germ-free mice. Clonally-arrayed sequenced collections of bacterial strains are constructed from representative donor microbiota. If the collection transmits phenotypes, effector strains are identified by testing randomly generated subsets with overlapping membership in individually-housed germ-free animals. Detailed mechanistic studies of effector strain-host interactions can then be performed. PMID:24950201

Stepwise molding, etching, and imprinting to form libraries of nanopatterned substrates.

PubMed

Zhao, Zhi; Cai, Yangjun; Liao, Wei-Ssu; Cremer, Paul S

2013-06-04

Herein, we describe a novel colloidal lithographic strategy for the stepwise patterning of planar substrates with numerous complex and unique designs. In conjunction with colloidal self-assembly, imprint molding, and capillary force lithography, reactive ion etching was used to create complex libraries of nanoscale features. This combinatorial strategy affords the ability to develop an exponentially increasing number of two-dimensional nanoscale patterns with each sequential step in the process. Specifically, dots, triangles, circles, and lines could be assembled on the surface separately and in combination with each other. Numerous architectures are obtained for the first time with high uniformity and reproducibility. These hexagonal arrays were made from polystyrene and gold features, whereby each surface element could be tuned from the micrometer size scale down to line widths of ~35 nm. The patterned area could be 1 cm(2) or even larger. The techniques described herein can be combined with further steps to make even larger libraries. Moreover, these polymer and metal features may prove useful in optical, sensing, and electronic applications.

Grid indentation analysis of mechanical properties of composite electrodes in Li-ion batteries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vasconcelos, Luize Scalco de; Xu, Rong; Li, Jianlin

We report that electrodes in commercial rechargeable batteries are microscopically heterogeneous materials. The constituent components, including active materials, polymeric binders, and porous conductive matrix, often have large variation in their mechanical properties, making the mechanical characterization of composite electrodes a challenging task. In a model system of LiNi 0.5Mn 0.3Co 0.2O 2 cathode, we employ the instrumented grid indentation to determine the elastic modulus and hardness of the constituent phases. The approach relies on a large array of nanoindentation experiments and statistical analysis of the resulting data provided that the maximum indentation depth is carefully chosen. The statistically extracted propertiesmore » of the active particles and the surrounding medium are in good agreement with the tests of targeted indentation at selected sites. Lastly, the combinatory technique of grid indentation and statistical deconvolution represents a fast and reliable route to quantify the mechanical properties of composite electrodes that feed the parametric input for the mechanics models.« less

Programmable disorder in random DNA tilings

NASA Astrophysics Data System (ADS)

Tikhomirov, Grigory; Petersen, Philip; Qian, Lulu

2017-03-01

Scaling up the complexity and diversity of synthetic molecular structures will require strategies that exploit the inherent stochasticity of molecular systems in a controlled fashion. Here we demonstrate a framework for programming random DNA tilings and show how to control the properties of global patterns through simple, local rules. We constructed three general forms of planar network—random loops, mazes and trees—on the surface of self-assembled DNA origami arrays on the micrometre scale with nanometre resolution. Using simple molecular building blocks and robust experimental conditions, we demonstrate control of a wide range of properties of the random networks, including the branching rules, the growth directions, the proximity between adjacent networks and the size distribution. Much as combinatorial approaches for generating random one-dimensional chains of polymers have been used to revolutionize chemical synthesis and the selection of functional nucleic acids, our strategy extends these principles to random two-dimensional networks of molecules and creates new opportunities for fabricating more complex molecular devices that are organized by DNA nanostructures.

Grid indentation analysis of mechanical properties of composite electrodes in Li-ion batteries

DOE PAGES

Vasconcelos, Luize Scalco de; Xu, Rong; Li, Jianlin; ...

2016-03-09

We report that electrodes in commercial rechargeable batteries are microscopically heterogeneous materials. The constituent components, including active materials, polymeric binders, and porous conductive matrix, often have large variation in their mechanical properties, making the mechanical characterization of composite electrodes a challenging task. In a model system of LiNi 0.5Mn 0.3Co 0.2O 2 cathode, we employ the instrumented grid indentation to determine the elastic modulus and hardness of the constituent phases. The approach relies on a large array of nanoindentation experiments and statistical analysis of the resulting data provided that the maximum indentation depth is carefully chosen. The statistically extracted propertiesmore » of the active particles and the surrounding medium are in good agreement with the tests of targeted indentation at selected sites. Lastly, the combinatory technique of grid indentation and statistical deconvolution represents a fast and reliable route to quantify the mechanical properties of composite electrodes that feed the parametric input for the mechanics models.« less

Compressed sensing approach for wrist vein biometrics.

PubMed

Lantsov, Aleksey; Ryabko, Maxim; Shchekin, Aleksey

2018-04-01

The work describes features of the compressed sensing (CS) approach utilized for development of a wearable system for wrist vein recognition with single-pixel detection; we consider this system useful for biometrics authentication purposes. The CS approach implies use of a spatial light modulation (SLM) which, in our case, can be performed differently-with a liquid crystal display or diffusely scattering medium. We show that compressed sensing combined with above-mentioned means of SLM allows us to avoid using an optical system-a limiting factor for wearable devices. The trade-off between the 2 different SLM approaches regarding issues of practical implementation of CS approach for wrist vein recognition purposes is discussed. A possible solution of a misalignment problem-a typical issue for imaging systems based upon 2D arrays of photodiodes-is also proposed. Proposed design of the wearable device for wrist vein recognition is based upon single-pixel detection. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Using Speech Recognition to Enhance the Tongue Drive System Functionality in Computer Access

PubMed Central

Huo, Xueliang; Ghovanloo, Maysam

2013-01-01

Tongue Drive System (TDS) is a wireless tongue operated assistive technology (AT), which can enable people with severe physical disabilities to access computers and drive powered wheelchairs using their volitional tongue movements. TDS offers six discrete commands, simultaneously available to the users, for pointing and typing as a substitute for mouse and keyboard in computer access, respectively. To enhance the TDS performance in typing, we have added a microphone, an audio codec, and a wireless audio link to its readily available 3-axial magnetic sensor array, and combined it with a commercially available speech recognition software, the Dragon Naturally Speaking, which is regarded as one of the most efficient ways for text entry. Our preliminary evaluations indicate that the combined TDS and speech recognition technologies can provide end users with significantly higher performance than using each technology alone, particularly in completing tasks that require both pointing and text entry, such as web surfing. PMID:22255801

Chair alarm for patient fall prevention based on gesture recognition and interactivity.

PubMed

Knight, Heather; Lee, Jae-Kyu; Ma, Hongshen

2008-01-01

The Gesture Recognition Interactive Technology (GRiT) Chair Alarm aims to prevent patient falls from chairs and wheelchairs by recognizing the gesture of a patient attempting to stand. Patient falls are one of the greatest causes of injury in hospitals. Current chair and bed exit alarm systems are inadequate because of insufficient notification, high false-alarm rate, and long trigger delays. The GRiT chair alarm uses an array of capacitive proximity sensors and pressure sensors to create a map of the patient's sitting position, which is then processed using gesture recognition algorithms to determine when a patient is attempting to stand and to alarm the care providers. This system also uses a range of voice and light feedback to encourage the patient to remain seated and/or to make use of the system's integrated nurse-call function. This system can be seamlessly integrated into existing hospital WiFi networks to send notifications and approximate patient location through existing nurse call systems.

Quick acquisition and recognition method for the beacon in deep space optical communications.

PubMed

Wang, Qiang; Liu, Yuefei; Ma, Jing; Tan, Liying; Yu, Siyuan; Li, Changjiang

2016-12-01

In deep space optical communications, it is very difficult to acquire the beacon given the long communication distance. Acquisition efficiency is essential for establishing and holding the optical communication link. Here we proposed a quick acquisition and recognition method for the beacon in deep optical communications based on the characteristics of the deep optical link. To identify the beacon from the background light efficiently, we utilized the maximum similarity between the collecting image and the reference image for accurate recognition and acquisition of the beacon in the area of uncertainty. First, the collecting image and the reference image were processed by Fourier-Mellin. Second, image sampling and image matching were applied for the accurate positioning of the beacon. Finally, the field programmable gate array (FPGA)-based system was used to verify and realize this method. The experimental results showed that the acquisition time for the beacon was as fast as 8.1s. Future application of this method in the system design of deep optical communication will be beneficial.

Bioinspired Methodology for Artificial Olfaction

PubMed Central

Raman, Baranidharan; Hertz, Joshua L.; Benkstein, Kurt D.; Semancik, Steve

2008-01-01

Artificial olfaction is a potential tool for noninvasive chemical monitoring. Application of “electronic noses” typically involves recognition of “pretrained” chemicals, while long-term operation and generalization of training to allow chemical classification of “unknown” analytes remain challenges. The latter analytical capability is critically important, as it is unfeasible to pre-expose the sensor to every analyte it might encounter. Here, we demonstrate a biologically inspired approach where the recognition and generalization problems are decoupled and resolved in a hierarchical fashion. Analyte composition is refined in a progression from general (e.g., target is a hydrocarbon) to precise (e.g., target is ethane), using highly optimized response features for each step. We validate this approach using a MEMS-based chemiresistive microsensor array. We show that this approach, a unique departure from existing methodologies in artificial olfaction, allows the recognition module to better mitigate sensor-aging effects and to better classify unknowns, enhancing the utility of chemical sensors for real-world applications. PMID:18855409

Point spread function engineering for iris recognition system design.

PubMed

Ashok, Amit; Neifeld, Mark A

2010-04-01

Undersampling in the detector array degrades the performance of iris-recognition imaging systems. We find that an undersampling of 8 x 8 reduces the iris-recognition performance by nearly a factor of 4 (on CASIA iris database), as measured by the false rejection ratio (FRR) metric. We employ optical point spread function (PSF) engineering via a Zernike phase mask in conjunction with multiple subpixel shifted image measurements (frames) to mitigate the effect of undersampling. A task-specific optimization framework is used to engineer the optical PSF and optimize the postprocessing parameters to minimize the FRR. The optimized Zernike phase enhanced lens (ZPEL) imager design with one frame yields an improvement of nearly 33% relative to a thin observation module by bounded optics (TOMBO) imager with one frame. With four frames the optimized ZPEL imager achieves a FRR equal to that of the conventional imager without undersampling. Further, the ZPEL imager design using 16 frames yields a FRR that is actually 15% lower than that obtained with the conventional imager without undersampling.

RRAM-based parallel computing architecture using k-nearest neighbor classification for pattern recognition

NASA Astrophysics Data System (ADS)

Jiang, Yuning; Kang, Jinfeng; Wang, Xinan

2017-03-01

Resistive switching memory (RRAM) is considered as one of the most promising devices for parallel computing solutions that may overcome the von Neumann bottleneck of today’s electronic systems. However, the existing RRAM-based parallel computing architectures suffer from practical problems such as device variations and extra computing circuits. In this work, we propose a novel parallel computing architecture for pattern recognition by implementing k-nearest neighbor classification on metal-oxide RRAM crossbar arrays. Metal-oxide RRAM with gradual RESET behaviors is chosen as both the storage and computing components. The proposed architecture is tested by the MNIST database. High speed (~100 ns per example) and high recognition accuracy (97.05%) are obtained. The influence of several non-ideal device properties is also discussed, and it turns out that the proposed architecture shows great tolerance to device variations. This work paves a new way to achieve RRAM-based parallel computing hardware systems with high performance.

Conserved conformational selection mechanism of Hsp70 chaperone-substrate interactions

PubMed Central

Velyvis, Algirdas; Zoltsman, Guy; Rosenzweig, Rina; Bouvignies, Guillaume

2018-01-01

Molecular recognition is integral to biological function and frequently involves preferred binding of a molecule to one of several exchanging ligand conformations in solution. In such a process the bound structure can be selected from the ensemble of interconverting ligands a priori (conformational selection, CS) or may form once the ligand is bound (induced fit, IF). Here we focus on the ubiquitous and conserved Hsp70 chaperone which oversees the integrity of the cellular proteome through its ATP-dependent interaction with client proteins. We directly quantify the flux along CS and IF pathways using solution NMR spectroscopy that exploits a methyl TROSY effect and selective isotope-labeling methodologies. Our measurements establish that both bacterial and human Hsp70 chaperones interact with clients by selecting the unfolded state from a pre-existing array of interconverting structures, suggesting a conserved mode of client recognition among Hsp70s and highlighting the importance of molecular dynamics in this recognition event. PMID:29460778

The relationship between speech recognition, behavioural listening effort, and subjective ratings.

PubMed

Picou, Erin M; Ricketts, Todd A

2018-06-01

The purpose of this study was to evaluate the reliability and validity of four subjective questions related to listening effort. A secondary purpose of this study was to evaluate the effects of hearing aid beamforming microphone arrays on word recognition and listening effort. Participants answered subjective questions immediately following testing in a dual-task paradigm with three microphone settings in a moderately reverberant laboratory environment in two noise configurations. Participants rated their: (1) mental work, (2) desire to improve the situation, (3) tiredness, and (4) desire to give up. Data were analysed using repeated measures and reliability analyses. Eighteen adults with symmetrical sensorineural hearing loss participated. Beamforming differentially affected word recognition and listening effort. Analysis revealed the same pattern of results for behavioural listening effort and subjective ratings of desire to improve the situation. Conversely, ratings of work revealed the same pattern of results as word recognition performance. Ratings of tiredness and desire to give up were unaffected by hearing aid microphone or noise configuration. Participant ratings of their desire to control the listening situation appear to reliable subjective indicators of listening effort that align with results from a behavioural measure of listening effort.

Neuroelectric Virtual Devices

NASA Technical Reports Server (NTRS)

Wheeler, Kevin; Jorgensen, Charles

2000-01-01

This paper presents recent results in neuroelectric pattern recognition of electromyographic (EMG) signals used to control virtual computer input devices. The devices are designed to substitute for the functions of both a traditional joystick and keyboard entry method. We demonstrate recognition accuracy through neuroelectric control of a 757 class simulation aircraft landing at San Francisco International Airport using a virtual joystick as shown. This is accomplished by a pilot closing his fist in empty air and performing control movements that are captured by a dry electrode array on the arm which are then analyzed and routed through a flight director permitting full pilot outer loop control of the simulation. We then demonstrate finer grain motor pattern recognition through a virtual keyboard by having a typist tap his traders on a typical desk in a touch typist position. The EMG signals are then translated to keyboard presses and displayed. The paper describes the bioelectric pattern recognition methodology common to both examples. Figure 2 depicts raw EMG data from typing, the numeral '8' and the numeral '9'. These two gestures are very close in appearance and statistical properties yet are distinguishable by our hidden Kharkov model algorithms. Extensions of this work to NASA emissions and robotic control are considered.

New pattern recognition system in the e-nose for Chinese spirit identification

NASA Astrophysics Data System (ADS)

Hui, Zeng; Qiang, Li; Yu, Gu

2016-02-01

This paper presents a new pattern recognition system for Chinese spirit identification by using the polymer quartz piezoelectric crystal sensor based e-nose. The sensors are designed based on quartz crystal microbalance (QCM) principle, and they could capture different vibration frequency signal values for Chinese spirit identification. For each sensor in an 8-channel sensor array, seven characteristic values of the original vibration frequency signal values, i.e., average value (A), root-mean-square value (RMS), shape factor value (Sf), crest factor value (Cf), impulse factor value (If), clearance factor value (CLf), kurtosis factor value (Kv) are first extracted. Then the dimension of the characteristic values is reduced by the principle components analysis (PCA) method. Finally the back propagation (BP) neutral network algorithm is used to recognize Chinese spirits. The experimental results show that the recognition rate of six kinds of Chinese spirits is 93.33% and our proposed new pattern recognition system can identify Chinese spirits effectively. Project supported by the National High Technology Research and Development Program of China (Grant No. 2013AA030901) and the Fundamental Research Funds for the Central Universities, China (Grant No. FRF-TP-14-120A2).

Emotion-attention interactions in recognition memory for distractor faces.

PubMed

Srinivasan, Narayanan; Gupta, Rashmi

2010-04-01

Effective filtering of distractor information has been shown to be dependent on perceptual load. Given the salience of emotional information and the presence of emotion-attention interactions, we wanted to explore the recognition memory for emotional distractors especially as a function of focused attention and distributed attention by manipulating load and the spatial spread of attention. We performed two experiments to study emotion-attention interactions by measuring recognition memory performance for distractor neutral and emotional faces. Participants performed a color discrimination task (low-load) or letter identification task (high-load) with a letter string display in Experiment 1 and a high-load letter identification task with letters presented in a circular array in Experiment 2. The stimuli were presented against a distractor face background. The recognition memory results show that happy faces were recognized better than sad faces under conditions of less focused or distributed attention. When attention is more spatially focused, sad faces were recognized better than happy faces. The study provides evidence for emotion-attention interactions in which specific emotional information like sad or happy is associated with focused or distributed attention respectively. Distractor processing with emotional information also has implications for theories of attention. Copyright 2010 APA, all rights reserved.

Automated Combinatorial Chemistry in the Organic Chemistry Majors Laboratory

ERIC Educational Resources Information Center

Nichols, Christopher J.; Hanne, Larry F.

2010-01-01

A multidisciplinary experiment has been developed in which students each synthesize a combinatorial library of 48 hydrazones with the aid of a liquid-handling robot. Each product is then subjected to a Kirby-Bauer disk diffusion assay to assess its antibacterial activity. Students gain experience working with automation and at the…

More Combinatorial Proofs via Flagpole Arrangements

ERIC Educational Resources Information Center

DeTemple, Duane; Reynolds, H. David, II

2006-01-01

Combinatorial identities are proved by counting the number of arrangements of a flagpole and guy wires on a row of blocks that satisfy a set of conditions. An identity is proved by first deriving and then equating two expressions that each count the number of permissible arrangements. Identities for binomial coefficients and recursion relations…

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

ERIC Educational Resources Information Center

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…

Children's Strategies for Solving Two- and Three-Dimensional Combinatorial Problems.

ERIC Educational Resources Information Center

English, Lyn D.

1993-01-01

Investigated strategies that 7- to 12-year-old children (n=96) spontaneously applied in solving novel combinatorial problems. With experience in solving two-dimensional problems, children were able to refine their strategies and adapt them to three dimensions. Results on some problems indicated significant effects of age. (Contains 32 references.)…

Identities for Generalized Fibonacci Numbers: A Combinatorial Approach

ERIC Educational Resources Information Center

Plaza, A.; Falcon, S.

2008-01-01

This note shows a combinatorial approach to some identities for generalized Fibonacci numbers. While it is a straightforward task to prove these identities with induction, and also by arithmetical manipulations such as rearrangements, the approach used here is quite simple to follow and eventually reduces the proof to a counting problem. (Contains…

Combinatorial Partial Hydrogenation Reactions of 4-Nitroacetophenone: An Undergraduate Organic Laboratory

ERIC Educational Resources Information Center

Kittredge, Kevin W.; Marine, Susan S.; Taylor, Richard T.

2004-01-01

A molecule possessing other functional groups that could be hydrogenerated is examined, where a variety of metal catalysts are evaluated under similar reaction conditions. Optimizing organic reactions is both time and labor intensive, and the use of a combinatorial parallel synthesis reactor was great time saving device, as per summary.

Human Performance on the Traveling Salesman and Related Problems: A Review

ERIC Educational Resources Information Center

MacGregor, James N.; Chu, Yun

2011-01-01

The article provides a review of recent research on human performance on the traveling salesman problem (TSP) and related combinatorial optimization problems. We discuss what combinatorial optimization problems are, why they are important, and why they may be of interest to cognitive scientists. We next describe the main characteristics of human…

Heuristic Implementation of Dynamic Programming for Matrix Permutation Problems in Combinatorial Data Analysis

ERIC Educational Resources Information Center

Brusco, Michael J.; Kohn, Hans-Friedrich; Stahl, Stephanie

2008-01-01

Dynamic programming methods for matrix permutation problems in combinatorial data analysis can produce globally-optimal solutions for matrices up to size 30x30, but are computationally infeasible for larger matrices because of enormous computer memory requirements. Branch-and-bound methods also guarantee globally-optimal solutions, but computation…

Iconicity and the Emergence of Combinatorial Structure in Language

ERIC Educational Resources Information Center

Verhoef, Tessa; Kirby, Simon; de Boer, Bart

2016-01-01

In language, recombination of a discrete set of meaningless building blocks forms an unlimited set of possible utterances. How such combinatorial structure emerged in the evolution of human language is increasingly being studied. It has been shown that it can emerge when languages culturally evolve and adapt to human cognitive biases. How the…

Crossover versus mutation: a comparative analysis of the evolutionary strategy of genetic algorithms applied to combinatorial optimization problems.

PubMed

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.

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

PubMed Central

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

Novel design strategy for checkpoint kinase 2 inhibitors using pharmacophore modeling, combinatorial fusion, and virtual screening.

PubMed

Lin, Chun-Yuan; Wang, Yen-Ling

2014-01-01

Checkpoint kinase 2 (Chk2) has a great effect on DNA-damage and plays an important role in response to DNA double-strand breaks and related lesions. In this study, we will concentrate on Chk2 and the purpose is to find the potential inhibitors by the pharmacophore hypotheses (PhModels), combinatorial fusion, and virtual screening techniques. Applying combinatorial fusion into PhModels and virtual screening techniques is a novel design strategy for drug design. We used combinatorial fusion to analyze the prediction results and then obtained the best correlation coefficient of the testing set (r test) with the value 0.816 by combining the Best(train)Best(test) and Fast(train)Fast(test) prediction results. The potential inhibitors were selected from NCI database by screening according to Best(train)Best(test) + Fast(train)Fast(test) prediction results and molecular docking with CDOCKER docking program. Finally, the selected compounds have high interaction energy between a ligand and a receptor. Through these approaches, 23 potential inhibitors for Chk2 are retrieved for further study.

A combinatorial filtering method for magnetotelluric time-series based on Hilbert-Huang transform

NASA Astrophysics Data System (ADS)

Cai, Jianhua

2014-11-01

Magnetotelluric (MT) time-series are often contaminated with noise from natural or man-made processes. A substantial improvement is possible when the time-series are presented as clean as possible for further processing. A combinatorial method is described for filtering of MT time-series based on the Hilbert-Huang transform that requires a minimum of human intervention and leaves good data sections unchanged. Good data sections are preserved because after empirical mode decomposition the data are analysed through hierarchies, morphological filtering, adaptive threshold and multi-point smoothing, allowing separation of noise from signals. The combinatorial method can be carried out without any assumption about the data distribution. Simulated data and the real measured MT time-series from three different regions, with noise caused by baseline drift, high frequency noise and power-line contribution, are processed to demonstrate the application of the proposed method. Results highlight the ability of the combinatorial method to pick out useful signals, and the noise is suppressed greatly so that their deleterious influence is eliminated for the MT transfer function estimation.

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

PubMed

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.

Combinatorial Characterization of TiO2 Chemical Vapor Deposition Utilizing Titanium Isopropoxide.

PubMed

Reinke, Michael; Ponomarev, Evgeniy; Kuzminykh, Yury; Hoffmann, Patrik

2015-07-13

The combinatorial characterization of the growth kinetics in chemical vapor deposition processes is challenging because precise information about the local precursor flow is usually difficult to access. In consequence, combinatorial chemical vapor deposition techniques are utilized more to study functional properties of thin films as a function of chemical composition, growth rate or crystallinity than to study the growth process itself. We present an experimental procedure which allows the combinatorial study of precursor surface kinetics during the film growth using high vacuum chemical vapor deposition. As consequence of the high vacuum environment, the precursor transport takes place in the molecular flow regime, which allows predicting and modifying precursor impinging rates on the substrate with comparatively little experimental effort. In this contribution, we study the surface kinetics of titanium dioxide formation using titanium tetraisopropoxide as precursor molecule over a large parameter range. We discuss precursor flux and temperature dependent morphology, crystallinity, growth rates, and precursor deposition efficiency. We conclude that the surface reaction of the adsorbed precursor molecules comprises a higher order reaction component with respect to precursor surface coverage.