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Sample records for protein design methods

  1. Deep sequencing methods for protein engineering and design.

    Science.gov (United States)

    Wrenbeck, Emily E; Faber, Matthew S; Whitehead, Timothy A

    2017-08-01

    The advent of next-generation sequencing (NGS) has revolutionized protein science, and the development of complementary methods enabling NGS-driven protein engineering have followed. In general, these experiments address the functional consequences of thousands of protein variants in a massively parallel manner using genotype-phenotype linked high-throughput functional screens followed by DNA counting via deep sequencing. We highlight the use of information rich datasets to engineer protein molecular recognition. Examples include the creation of multiple dual-affinity Fabs targeting structurally dissimilar epitopes and engineering of a broad germline-targeted anti-HIV-1 immunogen. Additionally, we highlight the generation of enzyme fitness landscapes for conducting fundamental studies of protein behavior and evolution. We conclude with discussion of technological advances. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Designing Focused Chemical Libraries Enriched in Protein-Protein Interaction Inhibitors using Machine-Learning Methods

    Science.gov (United States)

    Reynès, Christelle; Host, Hélène; Camproux, Anne-Claude; Laconde, Guillaume; Leroux, Florence; Mazars, Anne; Deprez, Benoit; Fahraeus, Robin; Villoutreix, Bruno O.; Sperandio, Olivier

    2010-01-01

    Protein-protein interactions (PPIs) may represent one of the next major classes of therapeutic targets. So far, only a minute fraction of the estimated 650,000 PPIs that comprise the human interactome are known with a tiny number of complexes being drugged. Such intricate biological systems cannot be cost-efficiently tackled using conventional high-throughput screening methods. Rather, time has come for designing new strategies that will maximize the chance for hit identification through a rationalization of the PPI inhibitor chemical space and the design of PPI-focused compound libraries (global or target-specific). Here, we train machine-learning-based models, mainly decision trees, using a dataset of known PPI inhibitors and of regular drugs in order to determine a global physico-chemical profile for putative PPI inhibitors. This statistical analysis unravels two important molecular descriptors for PPI inhibitors characterizing specific molecular shapes and the presence of a privileged number of aromatic bonds. The best model has been transposed into a computer program, PPI-HitProfiler, that can output from any drug-like compound collection a focused chemical library enriched in putative PPI inhibitors. Our PPI inhibitor profiler is challenged on the experimental screening results of 11 different PPIs among which the p53/MDM2 interaction screened within our own CDithem platform, that in addition to the validation of our concept led to the identification of 4 novel p53/MDM2 inhibitors. Collectively, our tool shows a robust behavior on the 11 experimental datasets by correctly profiling 70% of the experimentally identified hits while removing 52% of the inactive compounds from the initial compound collections. We strongly believe that this new tool can be used as a global PPI inhibitor profiler prior to screening assays to reduce the size of the compound collections to be experimentally screened while keeping most of the true PPI inhibitors. PPI-HitProfiler is

  3. Designing focused chemical libraries enriched in protein-protein interaction inhibitors using machine-learning methods.

    Directory of Open Access Journals (Sweden)

    Christelle Reynès

    2010-03-01

    Full Text Available Protein-protein interactions (PPIs may represent one of the next major classes of therapeutic targets. So far, only a minute fraction of the estimated 650,000 PPIs that comprise the human interactome are known with a tiny number of complexes being drugged. Such intricate biological systems cannot be cost-efficiently tackled using conventional high-throughput screening methods. Rather, time has come for designing new strategies that will maximize the chance for hit identification through a rationalization of the PPI inhibitor chemical space and the design of PPI-focused compound libraries (global or target-specific. Here, we train machine-learning-based models, mainly decision trees, using a dataset of known PPI inhibitors and of regular drugs in order to determine a global physico-chemical profile for putative PPI inhibitors. This statistical analysis unravels two important molecular descriptors for PPI inhibitors characterizing specific molecular shapes and the presence of a privileged number of aromatic bonds. The best model has been transposed into a computer program, PPI-HitProfiler, that can output from any drug-like compound collection a focused chemical library enriched in putative PPI inhibitors. Our PPI inhibitor profiler is challenged on the experimental screening results of 11 different PPIs among which the p53/MDM2 interaction screened within our own CDithem platform, that in addition to the validation of our concept led to the identification of 4 novel p53/MDM2 inhibitors. Collectively, our tool shows a robust behavior on the 11 experimental datasets by correctly profiling 70% of the experimentally identified hits while removing 52% of the inactive compounds from the initial compound collections. We strongly believe that this new tool can be used as a global PPI inhibitor profiler prior to screening assays to reduce the size of the compound collections to be experimentally screened while keeping most of the true PPI inhibitors. PPI

  4. Designing focused chemical libraries enriched in protein-protein interaction inhibitors using machine-learning methods.

    Science.gov (United States)

    Reynès, Christelle; Host, Hélène; Camproux, Anne-Claude; Laconde, Guillaume; Leroux, Florence; Mazars, Anne; Deprez, Benoit; Fahraeus, Robin; Villoutreix, Bruno O; Sperandio, Olivier

    2010-03-05

    Protein-protein interactions (PPIs) may represent one of the next major classes of therapeutic targets. So far, only a minute fraction of the estimated 650,000 PPIs that comprise the human interactome are known with a tiny number of complexes being drugged. Such intricate biological systems cannot be cost-efficiently tackled using conventional high-throughput screening methods. Rather, time has come for designing new strategies that will maximize the chance for hit identification through a rationalization of the PPI inhibitor chemical space and the design of PPI-focused compound libraries (global or target-specific). Here, we train machine-learning-based models, mainly decision trees, using a dataset of known PPI inhibitors and of regular drugs in order to determine a global physico-chemical profile for putative PPI inhibitors. This statistical analysis unravels two important molecular descriptors for PPI inhibitors characterizing specific molecular shapes and the presence of a privileged number of aromatic bonds. The best model has been transposed into a computer program, PPI-HitProfiler, that can output from any drug-like compound collection a focused chemical library enriched in putative PPI inhibitors. Our PPI inhibitor profiler is challenged on the experimental screening results of 11 different PPIs among which the p53/MDM2 interaction screened within our own CDithem platform, that in addition to the validation of our concept led to the identification of 4 novel p53/MDM2 inhibitors. Collectively, our tool shows a robust behavior on the 11 experimental datasets by correctly profiling 70% of the experimentally identified hits while removing 52% of the inactive compounds from the initial compound collections. We strongly believe that this new tool can be used as a global PPI inhibitor profiler prior to screening assays to reduce the size of the compound collections to be experimentally screened while keeping most of the true PPI inhibitors. PPI-HitProfiler is

  5. Surfing the Protein-Protein Interaction Surface Using Docking Methods: Application to the Design of PPI Inhibitors

    Directory of Open Access Journals (Sweden)

    Rushikesh Sable

    2015-06-01

    Full Text Available Blocking protein-protein interactions (PPI using small molecules or peptides modulates biochemical pathways and has therapeutic significance. PPI inhibition for designing drug-like molecules is a new area that has been explored extensively during the last decade. Considering the number of available PPI inhibitor databases and the limited number of 3D structures available for proteins, docking and scoring methods play a major role in designing PPI inhibitors as well as stabilizers. Docking methods are used in the design of PPI inhibitors at several stages of finding a lead compound, including modeling the protein complex, screening for hot spots on the protein-protein interaction interface and screening small molecules or peptides that bind to the PPI interface. There are three major challenges to the use of docking on the relatively flat surfaces of PPI. In this review we will provide some examples of the use of docking in PPI inhibitor design as well as its limitations. The combination of experimental and docking methods with improved scoring function has thus far resulted in few success stories of PPI inhibitors for therapeutic purposes. Docking algorithms used for PPI are in the early stages, however, and as more data are available docking will become a highly promising area in the design of PPI inhibitors or stabilizers.

  6. Surfing the Protein-Protein Interaction Surface Using Docking Methods: Application to the Design of PPI Inhibitors.

    Science.gov (United States)

    Sable, Rushikesh; Jois, Seetharama

    2015-06-23

    Blocking protein-protein interactions (PPI) using small molecules or peptides modulates biochemical pathways and has therapeutic significance. PPI inhibition for designing drug-like molecules is a new area that has been explored extensively during the last decade. Considering the number of available PPI inhibitor databases and the limited number of 3D structures available for proteins, docking and scoring methods play a major role in designing PPI inhibitors as well as stabilizers. Docking methods are used in the design of PPI inhibitors at several stages of finding a lead compound, including modeling the protein complex, screening for hot spots on the protein-protein interaction interface and screening small molecules or peptides that bind to the PPI interface. There are three major challenges to the use of docking on the relatively flat surfaces of PPI. In this review we will provide some examples of the use of docking in PPI inhibitor design as well as its limitations. The combination of experimental and docking methods with improved scoring function has thus far resulted in few success stories of PPI inhibitors for therapeutic purposes. Docking algorithms used for PPI are in the early stages, however, and as more data are available docking will become a highly promising area in the design of PPI inhibitors or stabilizers.

  7. Computational Protein Design

    DEFF Research Database (Denmark)

    Johansson, Kristoffer Enøe

    Proteins are the major functional group of molecules in biology. The impact of protein science on medicine and chemical productions is rapidly increasing. However, the greatest potential remains to be realized. The fi eld of protein design has advanced computational modeling from a tool of support...... to a central method that enables new developments. For example, novel enzymes with functions not found in natural proteins have been de novo designed to give enough activity for experimental optimization. This thesis presents the current state-of-the-art within computational design methods together...... with a novel method based on probability theory. With the aim of assembling a complete pipeline for protein design, this work touches upon several aspects of protein design. The presented work is the computational half of a design project where the other half is dedicated to the experimental part...

  8. Structural test of the parameterized-backbone method for protein design.

    Science.gov (United States)

    Plecs, Joseph J; Harbury, Pehr B; Kim, Peter S; Alber, Tom

    2004-09-03

    Designing new protein folds requires a method for simultaneously optimizing the conformation of the backbone and the side-chains. One approach to this problem is the use of a parameterized backbone, which allows the systematic exploration of families of structures. We report the crystal structure of RH3, a right-handed, three-helix coiled coil that was designed using a parameterized backbone and detailed modeling of core packing. This crystal structure was determined using another rationally designed feature, a metal-binding site that permitted experimental phasing of the X-ray data. RH3 adopted the intended fold, which has not been observed previously in biological proteins. Unanticipated structural asymmetry in the trimer was a principal source of variation within the RH3 structure. The sequence of RH3 differs from that of a previously characterized right-handed tetramer, RH4, at only one position in each 11 amino acid sequence repeat. This close similarity indicates that the design method is sensitive to the core packing interactions that specify the protein structure. Comparison of the structures of RH3 and RH4 indicates that both steric overlap and cavity formation provide strong driving forces for oligomer specificity.

  9. Potato tuber proteomics: Comparison of two complementary extraction methods designed for 2-DE of acidic proteins

    NARCIS (Netherlands)

    Delaplace, P.; Wal, van der F.; Dierick, J.F.; Cordewener, J.H.G.; Fauconnier, M.L.; Jardin, du P.; America, A.H.P.

    2006-01-01

    Two protein extraction procedures were tested in order to remove interfering compounds prior to 2-DE of potato tubers. These methods using SDS lysis buffer and phenol-phase extraction were compared regarding the quality of the resulting 2-D gel. While the resolution of SDS extracts on

  10. Computational protein design: a review

    International Nuclear Information System (INIS)

    Coluzza, Ivan

    2017-01-01

    Proteins are one of the most versatile modular assembling systems in nature. Experimentally, more than 110 000 protein structures have been identified and more are deposited every day in the Protein Data Bank. Such an enormous structural variety is to a first approximation controlled by the sequence of amino acids along the peptide chain of each protein. Understanding how the structural and functional properties of the target can be encoded in this sequence is the main objective of protein design. Unfortunately, rational protein design remains one of the major challenges across the disciplines of biology, physics and chemistry. The implications of solving this problem are enormous and branch into materials science, drug design, evolution and even cryptography. For instance, in the field of drug design an effective computational method to design protein-based ligands for biological targets such as viruses, bacteria or tumour cells, could give a significant boost to the development of new therapies with reduced side effects. In materials science, self-assembly is a highly desired property and soon artificial proteins could represent a new class of designable self-assembling materials. The scope of this review is to describe the state of the art in computational protein design methods and give the reader an outline of what developments could be expected in the near future. (topical review)

  11. Protein-Protein Docking in Drug Design and Discovery.

    Science.gov (United States)

    Kaczor, Agnieszka A; Bartuzi, Damian; Stępniewski, Tomasz Maciej; Matosiuk, Dariusz; Selent, Jana

    2018-01-01

    Protein-protein interactions (PPIs) are responsible for a number of key physiological processes in the living cells and underlie the pathomechanism of many diseases. Nowadays, along with the concept of so-called "hot spots" in protein-protein interactions, which are well-defined interface regions responsible for most of the binding energy, these interfaces can be targeted with modulators. In order to apply structure-based design techniques to design PPIs modulators, a three-dimensional structure of protein complex has to be available. In this context in silico approaches, in particular protein-protein docking, are a valuable complement to experimental methods for elucidating 3D structure of protein complexes. Protein-protein docking is easy to use and does not require significant computer resources and time (in contrast to molecular dynamics) and it results in 3D structure of a protein complex (in contrast to sequence-based methods of predicting binding interfaces). However, protein-protein docking cannot address all the aspects of protein dynamics, in particular the global conformational changes during protein complex formation. In spite of this fact, protein-protein docking is widely used to model complexes of water-soluble proteins and less commonly to predict structures of transmembrane protein assemblies, including dimers and oligomers of G protein-coupled receptors (GPCRs). In this chapter we review the principles of protein-protein docking, available algorithms and software and discuss the recent examples, benefits, and drawbacks of protein-protein docking application to water-soluble proteins, membrane anchoring and transmembrane proteins, including GPCRs.

  12. Designing proteins for therapeutic applications.

    Science.gov (United States)

    Lazar, Greg A; Marshall, Shannon A; Plecs, Joseph J; Mayo, Stephen L; Desjarlais, John R

    2003-08-01

    Protein design is becoming an increasingly useful tool for optimizing protein drugs and creating novel biotherapeutics. Recent progress includes the engineering of monoclonal antibodies, cytokines, enzymes and viral fusion inhibitors.

  13. Computational design of protein interactions: designing proteins that neutralize influenza by inhibiting its hemagglutinin surface protein

    Science.gov (United States)

    Fleishman, Sarel

    2012-02-01

    Molecular recognition underlies all life processes. Design of interactions not seen in nature is a test of our understanding of molecular recognition and could unlock the vast potential of subtle control over molecular interaction networks, allowing the design of novel diagnostics and therapeutics for basic and applied research. We developed the first general method for designing protein interactions. The method starts by computing a region of high affinity interactions between dismembered amino acid residues and the target surface and then identifying proteins that can harbor these residues. Designs are tested experimentally for binding the target surface and successful ones are affinity matured using yeast cell surface display. Applied to the conserved stem region of influenza hemagglutinin we designed two unrelated proteins that, following affinity maturation, bound hemagglutinin at subnanomolar dissociation constants. Co-crystal structures of hemagglutinin bound to the two designed binders were within 1Angstrom RMSd of their models, validating the accuracy of the design strategy. One of the designed proteins inhibits the conformational changes that underlie hemagglutinin's cell-invasion functions and blocks virus infectivity in cell culture, suggesting that such proteins may in future serve as diagnostics and antivirals against a wide range of pathogenic influenza strains. We have used this method to obtain experimentally validated binders of several other target proteins, demonstrating the generality of the approach. We discuss the combination of modeling and high-throughput characterization of design variants which has been key to the success of this approach, as well as how we have used the data obtained in this project to enhance our understanding of molecular recognition. References: Science 332:816 JMB, in press Protein Sci 20:753

  14. Protein Design Using Unnatural Amino Acids

    Science.gov (United States)

    Bilgiçer, Basar; Kumar, Krishna

    2003-11-01

    With the increasing availability of whole organism genome sequences, understanding protein structure and function is of capital importance. Recent developments in the methodology of incorporation of unnatural amino acids into proteins allow the exploration of proteins at a very detailed level. Furthermore, de novo design of novel protein structures and function is feasible with unprecedented sophistication. Using examples from the literature, this article describes the available methods for unnatural amino acid incorporation and highlights some recent applications including the design of hyperstable protein folds.

  15. Design Methods in Practice

    DEFF Research Database (Denmark)

    Jensen, Torben Elgaard; Andreasen, Mogens Myrup

    2010-01-01

    The paper challenges the dominant and widespread view that a good design method will guarantee a systematic approach as well as certain results. First, it explores the substantial differences between on the one hand the conception of methods implied in Pahl & Beitz’s widely recognized text book...... on engineering design, and on the other hand the understanding of method use, which has emerged from micro-sociological studies of practice (ethnomethodology). Second, it reviews a number of case studies conducted by engineering students, who were instructed to investigate the actual use of design methods...... in Danish companies. The paper concludes that design methods in practice deviate substantially from Pahl & Beitz’s description of method use: The object and problems, which are the starting points for method use, are more contested and less given than generally assumed; The steps of methods are often...

  16. Embodied Design Ideation methods

    DEFF Research Database (Denmark)

    Wilde, Danielle; Vallgårda, Anna; Tomico, Oscar

    2017-01-01

    Embodied design ideation practices work with relationships between body, material and context to enliven design and research potential. Methods are often idiosyncratic and – due to their physical nature – not easily transferred. This presents challenges for designers wishing to develop and share ...

  17. Method card design dimensions

    DEFF Research Database (Denmark)

    Wölfel, Christiane; Merritt, T.

    2013-01-01

    There are many examples of cards used to assist or provide structure to the design process, yet there has not been a thorough articulation of the strengths and weaknesses of the various examples. We review eighteen card-based design tools in order to understand how they might benefit designers....... The card-based tools are explained in terms of five design dimensions including the intended purpose and scope of use, duration of use, methodology, customization, and formal/material qualities. Our analysis suggests three design patterns or archetypes for existing card-based design method tools...... and highlights unexplored areas in the design space. The paper concludes with recommendations for the future development of card-based methods for the field of interaction design....

  18. A platform analytical quality by design (AQbD) approach for multiple UHPLC-UV and UHPLC-MS methods development for protein analysis.

    Science.gov (United States)

    Kochling, Jianmei; Wu, Wei; Hua, Yimin; Guan, Qian; Castaneda-Merced, Juan

    2016-06-05

    A platform analytical quality by design approach for methods development is presented in this paper. This approach is not limited just to method development following the same logical Analytical quality by design (AQbD) process, it is also exploited across a range of applications in methods development with commonality in equipment and procedures. As demonstrated by the development process of 3 methods, the systematic approach strategy offers a thorough understanding of the method scientific strength. The knowledge gained from the UHPLC-UV peptide mapping method can be easily transferred to the UHPLC-MS oxidation method and the UHPLC-UV C-terminal heterogeneity methods of the same protein. In addition, the platform AQbD method development strategy ensures method robustness is built in during development. In early phases, a good method can generate reliable data for product development allowing confident decision making. Methods generated following the AQbD approach have great potential for avoiding extensive post-approval analytical method change. While in the commercial phase, high quality data ensures timely data release, reduced regulatory risk, and lowered lab operational cost. Moreover, large, reliable database and knowledge gained during AQbD method development provide strong justifications during regulatory filling for the selection of important parameters or parameter change needs for method validation, and help to justify for removal of unnecessary tests used for product specifications. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Protein design for pathway engineering.

    Science.gov (United States)

    Eriksen, Dawn T; Lian, Jiazhang; Zhao, Huimin

    2014-02-01

    Design and construction of biochemical pathways has increased the complexity of biosynthetically-produced compounds when compared to single enzyme biocatalysis. However, the coordination of multiple enzymes can introduce a complicated set of obstacles to overcome in order to achieve a high titer and yield of the desired compound. Metabolic engineering has made great strides in developing tools to optimize the flux through a target pathway, but the inherent characteristics of a particular enzyme within the pathway can still limit the productivity. Thus, judicious protein design is critical for metabolic and pathway engineering. This review will describe various strategies and examples of applying protein design to pathway engineering to optimize the flux through the pathway. The proteins can be engineered for altered substrate specificity/selectivity, increased catalytic activity, reduced mass transfer limitations through specific protein localization, and reduced substrate/product inhibition. Protein engineering can also be expanded to design biosensors to enable high through-put screening and to customize cell signaling networks. These strategies have successfully engineered pathways for significantly increased productivity of the desired product or in the production of novel compounds. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Protein design using continuous rotamers.

    Directory of Open Access Journals (Sweden)

    Pablo Gainza

    2012-01-01

    Full Text Available Optimizing amino acid conformation and identity is a central problem in computational protein design. Protein design algorithms must allow realistic protein flexibility to occur during this optimization, or they may fail to find the best sequence with the lowest energy. Most design algorithms implement side-chain flexibility by allowing the side chains to move between a small set of discrete, low-energy states, which we call rigid rotamers. In this work we show that allowing continuous side-chain flexibility (which we call continuous rotamers greatly improves protein flexibility modeling. We present a large-scale study that compares the sequences and best energy conformations in 69 protein-core redesigns using a rigid-rotamer model versus a continuous-rotamer model. We show that in nearly all of our redesigns the sequence found by the continuous-rotamer model is different and has a lower energy than the one found by the rigid-rotamer model. Moreover, the sequences found by the continuous-rotamer model are more similar to the native sequences. We then show that the seemingly easy solution of sampling more rigid rotamers within the continuous region is not a practical alternative to a continuous-rotamer model: at computationally feasible resolutions, using more rigid rotamers was never better than a continuous-rotamer model and almost always resulted in higher energies. Finally, we present a new protein design algorithm based on the dead-end elimination (DEE algorithm, which we call iMinDEE, that makes the use of continuous rotamers feasible in larger systems. iMinDEE guarantees finding the optimal answer while pruning the search space with close to the same efficiency of DEE.Software is available under the Lesser GNU Public License v3. Contact the authors for source code.

  1. Protein engineering of Bacillus acidopullulyticus pullulanase for enhanced thermostability using in silico data driven rational design methods.

    Science.gov (United States)

    Chen, Ana; Li, Yamei; Nie, Jianqi; McNeil, Brian; Jeffrey, Laura; Yang, Yankun; Bai, Zhonghu

    2015-10-01

    Thermostability has been considered as a requirement in the starch processing industry to maintain high catalytic activity of pullulanase under high temperatures. Four data driven rational design methods (B-FITTER, proline theory, PoPMuSiC-2.1, and sequence consensus approach) were adopted to identify the key residue potential links with thermostability, and 39 residues of Bacillus acidopullulyticus pullulanase were chosen as mutagenesis targets. Single mutagenesis followed by combined mutagenesis resulted in the best mutant E518I-S662R-Q706P, which exhibited an 11-fold half-life improvement at 60 °C and a 9.5 °C increase in Tm. The optimum temperature of the mutant increased from 60 to 65 °C. Fluorescence spectroscopy results demonstrated that the tertiary structure of the mutant enzyme was more compact than that of the wild-type (WT) enzyme. Structural change analysis revealed that the increase in thermostability was most probably caused by a combination of lower stability free-energy and higher hydrophobicity of E518I, more hydrogen bonds of S662R, and higher rigidity of Q706P compared with the WT. The findings demonstrated the effectiveness of combined data-driven rational design approaches in engineering an industrial enzyme to improve thermostability. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Gene design, cloning and protein-expression methods for high-value targets at the Seattle Structural Genomics Center for Infectious Disease

    International Nuclear Information System (INIS)

    Raymond, Amy; Haffner, Taryn; Ng, Nathan; Lorimer, Don; Staker, Bart; Stewart, Lance

    2011-01-01

    An overview of one salvage strategy for high-value SSGCID targets is given. Any structural genomics endeavor, particularly ambitious ones such as the NIAID-funded Seattle Structural Genomics Center for Infectious Disease (SSGCID) and Center for Structural Genomics of Infectious Disease (CSGID), face technical challenges at all points of the production pipeline. One salvage strategy employed by SSGCID is combined gene engineering and structure-guided construct design to overcome challenges at the levels of protein expression and protein crystallization. Multiple constructs of each target are cloned in parallel using Polymerase Incomplete Primer Extension cloning and small-scale expressions of these are rapidly analyzed by capillary electrophoresis. Using the methods reported here, which have proven particularly useful for high-value targets, otherwise intractable targets can be resolved

  3. Control system design method

    Science.gov (United States)

    Wilson, David G [Tijeras, NM; Robinett, III, Rush D.

    2012-02-21

    A control system design method and concomitant control system comprising representing a physical apparatus to be controlled as a Hamiltonian system, determining elements of the Hamiltonian system representation which are power generators, power dissipators, and power storage devices, analyzing stability and performance of the Hamiltonian system based on the results of the determining step and determining necessary and sufficient conditions for stability of the Hamiltonian system, creating a stable control system based on the results of the analyzing step, and employing the resulting control system to control the physical apparatus.

  4. Achievements and Challenges in Computational Protein Design.

    Science.gov (United States)

    Samish, Ilan

    2017-01-01

    Computational protein design (CPD), a yet evolving field, includes computer-aided engineering for partial or full de novo designs of proteins of interest. Designs are defined by a requested structure, function, or working environment. This chapter describes the birth and maturation of the field by presenting 101 CPD examples in a chronological order emphasizing achievements and pending challenges. Integrating these aspects presents the plethora of CPD approaches with the hope of providing a "CPD 101". These reflect on the broader structural bioinformatics and computational biophysics field and include: (1) integration of knowledge-based and energy-based methods, (2) hierarchical designated approach towards local, regional, and global motifs and the integration of high- and low-resolution design schemes that fit each such region, (3) systematic differential approaches towards different protein regions, (4) identification of key hot-spot residues and the relative effect of remote regions, (5) assessment of shape-complementarity, electrostatics and solvation effects, (6) integration of thermal plasticity and functional dynamics, (7) negative design, (8) systematic integration of experimental approaches, (9) objective cross-assessment of methods, and (10) successful ranking of potential designs. Future challenges also include dissemination of CPD software to the general use of life-sciences researchers and the emphasis of success within an in vivo milieu. CPD increases our understanding of protein structure and function and the relationships between the two along with the application of such know-how for the benefit of mankind. Applied aspects range from biological drugs, via healthier and tastier food products to nanotechnology and environmentally friendly enzymes replacing toxic chemicals utilized in the industry.

  5. Different protein-protein interface patterns predicted by different machine learning methods.

    Science.gov (United States)

    Wang, Wei; Yang, Yongxiao; Yin, Jianxin; Gong, Xinqi

    2017-11-22

    Different types of protein-protein interactions make different protein-protein interface patterns. Different machine learning methods are suitable to deal with different types of data. Then, is it the same situation that different interface patterns are preferred for prediction by different machine learning methods? Here, four different machine learning methods were employed to predict protein-protein interface residue pairs on different interface patterns. The performances of the methods for different types of proteins are different, which suggest that different machine learning methods tend to predict different protein-protein interface patterns. We made use of ANOVA and variable selection to prove our result. Our proposed methods taking advantages of different single methods also got a good prediction result compared to single methods. In addition to the prediction of protein-protein interactions, this idea can be extended to other research areas such as protein structure prediction and design.

  6. A maximum likelihood framework for protein design

    Directory of Open Access Journals (Sweden)

    Philippe Hervé

    2006-06-01

    Full Text Available Abstract Background The aim of protein design is to predict amino-acid sequences compatible with a given target structure. Traditionally envisioned as a purely thermodynamic question, this problem can also be understood in a wider context, where additional constraints are captured by learning the sequence patterns displayed by natural proteins of known conformation. In this latter perspective, however, we still need a theoretical formalization of the question, leading to general and efficient learning methods, and allowing for the selection of fast and accurate objective functions quantifying sequence/structure compatibility. Results We propose a formulation of the protein design problem in terms of model-based statistical inference. Our framework uses the maximum likelihood principle to optimize the unknown parameters of a statistical potential, which we call an inverse potential to contrast with classical potentials used for structure prediction. We propose an implementation based on Markov chain Monte Carlo, in which the likelihood is maximized by gradient descent and is numerically estimated by thermodynamic integration. The fit of the models is evaluated by cross-validation. We apply this to a simple pairwise contact potential, supplemented with a solvent-accessibility term, and show that the resulting models have a better predictive power than currently available pairwise potentials. Furthermore, the model comparison method presented here allows one to measure the relative contribution of each component of the potential, and to choose the optimal number of accessibility classes, which turns out to be much higher than classically considered. Conclusion Altogether, this reformulation makes it possible to test a wide diversity of models, using different forms of potentials, or accounting for other factors than just the constraint of thermodynamic stability. Ultimately, such model-based statistical analyses may help to understand the forces

  7. A Visual Language for Protein Design

    KAUST Repository

    Cox, Robert Sidney

    2017-02-08

    As protein engineering becomes more sophisticated, practitioners increasingly need to share diagrams for communicating protein designs. To this end, we present a draft visual language, Protein Language, that describes the high-level architecture of an engineered protein with easy-to draw glyphs, intended to be compatible with other biological diagram languages such as SBOL Visual and SBGN. Protein Language consists of glyphs for representing important features (e.g., globular domains, recognition and localization sequences, sites of covalent modification, cleavage and catalysis), rules for composing these glyphs to represent complex architectures, and rules constraining the scaling and styling of diagrams. To support Protein Language we have implemented an extensible web-based software diagram tool, Protein Designer, that uses Protein Language in a

  8. A Visual Language for Protein Design

    KAUST Repository

    Cox, Robert Sidney; McLaughlin, James Alastair; Grunberg, Raik; Beal, Jacob; Wipat, Anil; Sauro, Herbert M.

    2017-01-01

    As protein engineering becomes more sophisticated, practitioners increasingly need to share diagrams for communicating protein designs. To this end, we present a draft visual language, Protein Language, that describes the high-level architecture of an engineered protein with easy-to draw glyphs, intended to be compatible with other biological diagram languages such as SBOL Visual and SBGN. Protein Language consists of glyphs for representing important features (e.g., globular domains, recognition and localization sequences, sites of covalent modification, cleavage and catalysis), rules for composing these glyphs to represent complex architectures, and rules constraining the scaling and styling of diagrams. To support Protein Language we have implemented an extensible web-based software diagram tool, Protein Designer, that uses Protein Language in a

  9. Computational Studies of Protein Hydration Methods

    Science.gov (United States)

    Morozenko, Aleksandr

    It is widely appreciated that water plays a vital role in proteins' functions. The long-range proton transfer inside proteins is usually carried out by the Grotthuss mechanism and requires a chain of hydrogen bonds that is composed of internal water molecules and amino acid residues of the protein. In other cases, water molecules can facilitate the enzymes catalytic reactions by becoming a temporary proton donor/acceptor. Yet a reliable way of predicting water protein interior is still not available to the biophysics community. This thesis presents computational studies that have been performed to gain insights into the problems of fast and accurate prediction of potential water sites inside internal cavities of protein. Specifically, we focus on the task of attainment of correspondence between results obtained from computational experiments and experimental data available from X-ray structures. An overview of existing methods of predicting water molecules in the interior of a protein along with a discussion of the trustworthiness of these predictions is a second major subject of this thesis. A description of differences of water molecules in various media, particularly, gas, liquid and protein interior, and theoretical aspects of designing an adequate model of water for the protein environment are widely discussed in chapters 3 and 4. In chapter 5, we discuss recently developed methods of placement of water molecules into internal cavities of a protein. We propose a new methodology based on the principle of docking water molecules to a protein body which allows to achieve a higher degree of matching experimental data reported in protein crystal structures than other techniques available in the world of biophysical software. The new methodology is tested on a set of high-resolution crystal structures of oligopeptide-binding protein (OppA) containing a large number of resolved internal water molecules and applied to bovine heart cytochrome c oxidase in the fully

  10. Understanding Creativity Methods in Design

    DEFF Research Database (Denmark)

    Biskjaer, Michael Mose; Dalsgaard, Peter; Halskov, Kim

    2017-01-01

    This paper contributes an analytical framework to improve understanding of the composition of recognized creativity methods used in design. Based on an extensive literature review, our framework synthesizes key concepts from design and particularly creativity research, and is further supported...... by significant experience with creativity methods in design. We propose that nine concepts are relevant for analyzing creativity methods in design: process structure, materials, tools, combination, metaphor, analogy, framing, divergence, and convergence. To test their relevance as components of an analytical...... are composed, how and why they work, and how they potentially may be tweaked or refined for enhanced deployment in design....

  11. Creativity Methods in Interaction Design

    DEFF Research Database (Denmark)

    Biskjaer, Michael Mose; Dalsgaard, Peter; Halskov, Kim

    2010-01-01

    The field of interaction design encompasses a variety of methods for fostering innovation and creativity. In this paper, we present a selection of such methods that scaffold ideation and concept development in the early phases of design. As a conceptual frame for discussing these methods, we...... introduce four aspects that are particularly salient in the field of interaction design: tradition and transcendence, convergence and divergence, degree of structure, and sources of inspiration. We then outline how the methods relate to each of these aspects. The paper contributes to design practitioners...

  12. Algebraic Methods to Design Signals

    Science.gov (United States)

    2015-08-27

    to date on designing signals using algebraic and combinatorial methods. Mathematical tools from algebraic number theory, representation theory and... combinatorial objects in designing signals for communication purposes. Sequences and arrays with desirable autocorrelation properties have many...multiple access methods in mobile radio communication systems. We continue our mathematical framework based on group algebras, character theory

  13. High-resolution protein design with backbone freedom.

    Science.gov (United States)

    Harbury, P B; Plecs, J J; Tidor, B; Alber, T; Kim, P S

    1998-11-20

    Recent advances in computational techniques have allowed the design of precise side-chain packing in proteins with predetermined, naturally occurring backbone structures. Because these methods do not model protein main-chain flexibility, they lack the breadth to explore novel backbone conformations. Here the de novo design of a family of alpha-helical bundle proteins with a right-handed superhelical twist is described. In the design, the overall protein fold was specified by hydrophobic-polar residue patterning, whereas the bundle oligomerization state, detailed main-chain conformation, and interior side-chain rotamers were engineered by computational enumerations of packing in alternate backbone structures. Main-chain flexibility was incorporated through an algebraic parameterization of the backbone. The designed peptides form alpha-helical dimers, trimers, and tetramers in accord with the design goals. The crystal structure of the tetramer matches the designed structure in atomic detail.

  14. Designing a qualitative methods syllabus

    OpenAIRE

    Kier, Elizabeth

    2003-01-01

    After some initial trepidation, I was excited about teaching a graduate seminar in qualitative methods. It could hardly be a more interesting time. The publication of King, Keohane, and Verba’s Designing Social Inquiry reinvigorated interest in qualitative methods, and I wanted to design the course to profit from this emerging debate. Whereas KKV appealed to qualitative researchers to do their best to adopt quantitative methodological guidelines, I wanted to encourage students to think about ...

  15. Protein Crystallography: A 'Must' Technology for Drug Design

    International Nuclear Information System (INIS)

    Matsuzaki, Takao

    2004-01-01

    The history of drug-related protein crystallography and drug design is reviewed to show that 'Lead Generation' is high-lighted in the pharmaceutical industry nowadays. A new drug design method has been developed. The method gave very high success rate; 10-60 % gave < 100 μM, 90 % gave < 10 mM. The crystal structures of drug-protein complexes have become even more important to give solid experimental bases for e.g. 1,000 designed structures and to find the new mechanisms of drug action

  16. Recombinant protein blends: silk beyond natural design.

    Science.gov (United States)

    Dinjaski, Nina; Kaplan, David L

    2016-06-01

    Recombinant DNA technology and new material concepts are shaping future directions in biomaterial science for the design and production of the next-generation biomaterial platforms. Aside from conventionally used synthetic polymers, numerous natural biopolymers (e.g., silk, elastin, collagen, gelatin, alginate, cellulose, keratin, chitin, polyhydroxyalkanoates) have been investigated for properties and manipulation via bioengineering. Genetic engineering provides a path to increase structural and functional complexity of these biopolymers, and thereby expand the catalog of available biomaterials beyond that which exists in nature. In addition, the integration of experimental approaches with computational modeling to analyze sequence-structure-function relationships is starting to have an impact in the field by establishing predictive frameworks for determining material properties. Herein, we review advances in recombinant DNA-mediated protein production and functionalization approaches, with a focus on hybrids or combinations of proteins; recombinant protein blends or 'recombinamers'. We highlight the potential biomedical applications of fibrous protein recombinamers, such as Silk-Elastin Like Polypeptides (SELPs) and Silk-Bacterial Collagens (SBCs). We also discuss the possibility for the rationale design of fibrous proteins to build smart, stimuli-responsive biomaterials for diverse applications. We underline current limitations with production systems for these proteins and discuss the main trends in systems/synthetic biology that may improve recombinant fibrous protein design and production. Copyright © 2016. Published by Elsevier Ltd.

  17. Computational design of binding proteins to EGFR domain II.

    Directory of Open Access Journals (Sweden)

    Yoon Sup Choi

    Full Text Available We developed a process to produce novel interactions between two previously unrelated proteins. This process selects protein scaffolds and designs protein interfaces that bind to a surface patch of interest on a target protein. Scaffolds with shapes complementary to the target surface patch were screened using an exhaustive computational search of the human proteome and optimized by directed evolution using phage display. This method was applied to successfully design scaffolds that bind to epidermal growth factor receptor (EGFR domain II, the interface of EGFR dimerization, with high reactivity toward the target surface patch of EGFR domain II. One potential application of these tailor-made protein interactions is the development of therapeutic agents against specific protein targets.

  18. Botulinum neurotoxin: a marvel of protein design.

    Science.gov (United States)

    Montal, Mauricio

    2010-01-01

    Botulinum neurotoxin (BoNT), the causative agent of botulism, is acknowledged to be the most poisonous protein known. BoNT proteases disable synaptic vesicle exocytosis by cleaving their cytosolic SNARE (soluble NSF attachment protein receptor) substrates. BoNT is a modular nanomachine: an N-terminal Zn(2+)-metalloprotease, which cleaves the SNAREs; a central helical protein-conducting channel, which chaperones the protease across endosomes; and a C-terminal receptor-binding module, consisting of two subdomains that determine target specificity by binding to a ganglioside and a protein receptor on the cell surface and triggering endocytosis. For BoNT, functional complexity emerges from its modular design and the tight interplay between its component modules--a partnership with consequences that surpass the simple sum of the individual component's action. BoNTs exploit this design at each step of the intoxication process, thereby achieving an exquisite toxicity. This review summarizes current knowledge on the structure of individual modules and presents mechanistic insights into how this protein machine evolved to this level of sophistication. Understanding the design principles underpinning the function of such a dynamic modular protein remains a challenging task.

  19. Predicting the tolerated sequences for proteins and protein interfaces using RosettaBackrub flexible backbone design.

    Directory of Open Access Journals (Sweden)

    Colin A Smith

    Full Text Available Predicting the set of sequences that are tolerated by a protein or protein interface, while maintaining a desired function, is useful for characterizing protein interaction specificity and for computationally designing sequence libraries to engineer proteins with new functions. Here we provide a general method, a detailed set of protocols, and several benchmarks and analyses for estimating tolerated sequences using flexible backbone protein design implemented in the Rosetta molecular modeling software suite. The input to the method is at least one experimentally determined three-dimensional protein structure or high-quality model. The starting structure(s are expanded or refined into a conformational ensemble using Monte Carlo simulations consisting of backrub backbone and side chain moves in Rosetta. The method then uses a combination of simulated annealing and genetic algorithm optimization methods to enrich for low-energy sequences for the individual members of the ensemble. To emphasize certain functional requirements (e.g. forming a binding interface, interactions between and within parts of the structure (e.g. domains can be reweighted in the scoring function. Results from each backbone structure are merged together to create a single estimate for the tolerated sequence space. We provide an extensive description of the protocol and its parameters, all source code, example analysis scripts and three tests applying this method to finding sequences predicted to stabilize proteins or protein interfaces. The generality of this method makes many other applications possible, for example stabilizing interactions with small molecules, DNA, or RNA. Through the use of within-domain reweighting and/or multistate design, it may also be possible to use this method to find sequences that stabilize particular protein conformations or binding interactions over others.

  20. Rapid Sampling of Hydrogen Bond Networks for Computational Protein Design.

    Science.gov (United States)

    Maguire, Jack B; Boyken, Scott E; Baker, David; Kuhlman, Brian

    2018-05-08

    Hydrogen bond networks play a critical role in determining the stability and specificity of biomolecular complexes, and the ability to design such networks is important for engineering novel structures, interactions, and enzymes. One key feature of hydrogen bond networks that makes them difficult to rationally engineer is that they are highly cooperative and are not energetically favorable until the hydrogen bonding potential has been satisfied for all buried polar groups in the network. Existing computational methods for protein design are ill-equipped for creating these highly cooperative networks because they rely on energy functions and sampling strategies that are focused on pairwise interactions. To enable the design of complex hydrogen bond networks, we have developed a new sampling protocol in the molecular modeling program Rosetta that explicitly searches for sets of amino acid mutations that can form self-contained hydrogen bond networks. For a given set of designable residues, the protocol often identifies many alternative sets of mutations/networks, and we show that it can readily be applied to large sets of residues at protein-protein interfaces or in the interior of proteins. The protocol builds on a recently developed method in Rosetta for designing hydrogen bond networks that has been experimentally validated for small symmetric systems but was not extensible to many larger protein structures and complexes. The sampling protocol we describe here not only recapitulates previously validated designs with performance improvements but also yields viable hydrogen bond networks for cases where the previous method fails, such as the design of large, asymmetric interfaces relevant to engineering protein-based therapeutics.

  1. Numerical methods for metamaterial design

    CERN Document Server

    2013-01-01

    This book describes a relatively new approach for the design of electromagnetic metamaterials.  Numerical optimization routines are combined with electromagnetic simulations to tailor the broadband optical properties of a metamaterial to have predetermined responses at predetermined wavelengths. After a review of both the major efforts within the field of metamaterials and the field of mathematical optimization, chapters covering both gradient-based and derivative-free design methods are considered.  Selected topics including surrogate-base optimization, adaptive mesh search, and genetic algorithms are shown to be effective, gradient-free optimization strategies.  Additionally, new techniques for representing dielectric distributions in two dimensions, including level sets, are demonstrated as effective methods for gradient-based optimization.  Each chapter begins with a rigorous review of the optimization strategy used, and is followed by numerous examples that combine the strategy with either electromag...

  2. Optimization methods in structural design

    CERN Document Server

    Rothwell, Alan

    2017-01-01

    This book offers an introduction to numerical optimization methods in structural design. Employing a readily accessible and compact format, the book presents an overview of optimization methods, and equips readers to properly set up optimization problems and interpret the results. A ‘how-to-do-it’ approach is followed throughout, with less emphasis at this stage on mathematical derivations. The book features spreadsheet programs provided in Microsoft Excel, which allow readers to experience optimization ‘hands-on.’ Examples covered include truss structures, columns, beams, reinforced shell structures, stiffened panels and composite laminates. For the last three, a review of relevant analysis methods is included. Exercises, with solutions where appropriate, are also included with each chapter. The book offers a valuable resource for engineering students at the upper undergraduate and postgraduate level, as well as others in the industry and elsewhere who are new to these highly practical techniques.Whi...

  3. Direct methods in protein crystallography.

    Science.gov (United States)

    Karle, J

    1989-11-01

    It is pointed out that the 'direct methods' of phase determination for small-structure crystallography do not have immediate applicability to macromolecular structures. The term 'direct methods in macromolecular crystallography' is suggested to categorize a spectrum of approaches to macromolecular structure determination in which the analyses are characterized by the use of two-phase and higher-order-phase invariants. The evaluation of the invariants is generally obtained by the use of heavy-atom techniques. The results of a number of the more recent algebraic and probabilistic studies involving isomorphous replacement and anomalous dispersion thus become valid subjects for discussion here. These studies are described and suggestions are also presented concerning future applicability. Additional discussion concerns the special techniques of filtering, the use of non-crystallographic symmetry, some features of maximum entropy and attempts to apply phase-determining formulas to the refinement of macromolecular structure. It is noted that, in addition to the continuing remarkable progress in macromolecular crystallography based on the traditional applications of isomorphous replacement and anomalous dispersion, recent valuable advances have been made in the application of non-crystallographic symmetry, in particular, to virus structures and in applications of filtering. Good progress has also been reported in the application of exact linear algebra to multiple-wavelength anomalous-dispersion investigations of structures containing anomalous scatterers of only moderate scattering power.

  4. Finding protein sites using machine learning methods

    Directory of Open Access Journals (Sweden)

    Jaime Leonardo Bobadilla Molina

    2003-07-01

    Full Text Available The increasing amount of protein three-dimensional (3D structures determined by x-ray and NMR technologies as well as structures predicted by computational methods results in the need for automated methods to provide inital annotations. We have developed a new method for recognizing sites in three-dimensional protein structures. Our method is based on a previosly reported algorithm for creating descriptions of protein microenviroments using physical and chemical properties at multiple levels of detail. The recognition method takes three inputs: 1. A set of control nonsites that share some structural or functional role. 2. A set of control nonsites that lack this role. 3. A single query site. A support vector machine classifier is built using feature vectors where each component represents a property in a given volume. Validation against an independent test set shows that this recognition approach has high sensitivity and specificity. We also describe the results of scanning four calcium binding proteins (with the calcium removed using a three dimensional grid of probe points at 1.25 angstrom spacing. The system finds the sites in the proteins giving points at or near the blinding sites. Our results show that property based descriptions along with support vector machines can be used for recognizing protein sites in unannotated structures.

  5. Targeted proteins for diabetes drug design

    Science.gov (United States)

    Doan Trang Nguyen, Ngoc; Thi Le, Ly

    2012-03-01

    Type 2 diabetes mellitus is a common metabolism disorder characterized by high glucose in the bloodstream, especially in the case of insulin resistance and relative insulin deficiency. Nowadays, it is very common in middle-aged people and involves such dangerous symptoms as increasing risk of stroke, obesity and heart failure. In Vietnam, besides the common treatment of insulin injection, some herbal medication is used but no unified optimum remedy for the disease yet exists and there is no production of antidiabetic drugs in the domestic market yet. In the development of nanomedicine at the present time, drug design is considered as an innovative tool for researchers to study the mechanisms of diseases at the molecular level. The aim of this article is to review some common protein targets involved in type 2 diabetes, offering a new idea for designing new drug candidates to produce antidiabetic drugs against type 2 diabetes for Vietnamese people.

  6. Targeted proteins for diabetes drug design

    International Nuclear Information System (INIS)

    Trang Nguyen, Ngoc Doan; Le, Ly Thi

    2012-01-01

    Type 2 diabetes mellitus is a common metabolism disorder characterized by high glucose in the bloodstream, especially in the case of insulin resistance and relative insulin deficiency. Nowadays, it is very common in middle-aged people and involves such dangerous symptoms as increasing risk of stroke, obesity and heart failure. In Vietnam, besides the common treatment of insulin injection, some herbal medication is used but no unified optimum remedy for the disease yet exists and there is no production of antidiabetic drugs in the domestic market yet. In the development of nanomedicine at the present time, drug design is considered as an innovative tool for researchers to study the mechanisms of diseases at the molecular level. The aim of this article is to review some common protein targets involved in type 2 diabetes, offering a new idea for designing new drug candidates to produce antidiabetic drugs against type 2 diabetes for Vietnamese people. (review)

  7. Blood proteins analysis by Raman spectroscopy method

    Science.gov (United States)

    Artemyev, D. N.; Bratchenko, I. A.; Khristoforova, Yu. A.; Lykina, A. A.; Myakinin, O. O.; Kuzmina, T. P.; Davydkin, I. L.; Zakharov, V. P.

    2016-04-01

    This work is devoted to study the possibility of plasma proteins (albumin, globulins) concentration measurement using Raman spectroscopy setup. The blood plasma and whole blood were studied in this research. The obtained Raman spectra showed significant variation of intensities of certain spectral bands 940, 1005, 1330, 1450 and 1650 cm-1 for different protein fractions. Partial least squares regression analysis was used for determination of correlation coefficients. We have shown that the proposed method represents the structure and biochemical composition of major blood proteins.

  8. Electrostatic similarities between protein and small molecule ligands facilitate the design of protein-protein interaction inhibitors.

    Directory of Open Access Journals (Sweden)

    Arnout Voet

    Full Text Available One of the underlying principles in drug discovery is that a biologically active compound is complimentary in shape and molecular recognition features to its receptor. This principle infers that molecules binding to the same receptor may share some common features. Here, we have investigated whether the electrostatic similarity can be used for the discovery of small molecule protein-protein interaction inhibitors (SMPPIIs. We have developed a method that can be used to evaluate the similarity of electrostatic potentials between small molecules and known protein ligands. This method was implemented in a software called EleKit. Analyses of all available (at the time of research SMPPII structures indicate that SMPPIIs bear some similarities of electrostatic potential with the ligand proteins of the same receptor. This is especially true for the more polar SMPPIIs. Retrospective analysis of several successful SMPPIIs has shown the applicability of EleKit in the design of new SMPPIIs.

  9. Interrogation of an autofluorescence-based method for protein fingerprinting.

    Science.gov (United States)

    Siddaramaiah, Manjunath; Rao, Bola Sadashiva S; Joshi, Manjunath B; Datta, Anirbit; Sandya, S; Vishnumurthy, Vasudha; Chandra, Subhash; Nayak, Subramanya G; Satyamoorthy, Kapaettu; Mahato, Krishna K

    2018-03-14

    In the present study, we have designed a laser-induced fluorescence (LIF) based instrumentation and developed a sensitive methodology for the effective separation, visualization, identification and analysis of proteins on a single platform. In this method, intrinsic fluorescence spectra of proteins were detected after separation on 1 or 2 dimensional Sodium Dodecyl Sulfate-Tris(2-carboxyethyl)phosphine (SDS-TCEP) polyacrylamide gel electrophoresis (PAGE) and the data were analyzed. The MATLAB assisted software was designed for the development of PAGE fingerprint for the visualization of protein after 1- and 2-dimensional protein separation. These provided objective parameters of intrinsic fluorescence intensity, emission peak, molecular weight and isoelectric point using a single platform. Further, the current architecture could differentiate the overlapping proteins in the PAGE gels which otherwise were not identifiable by conventional staining, imaging and tagging methods. Categorization of the proteins based on the presence or absence of tyrosine or tryptophan residues and assigning the corresponding emission peaks (309-356 nm) with pseudo colors allowed the detection of proportion of proteins within the given spectrum. The present methodology doesn't use stains or tags, hence amenable to couple with mass spectroscopic measurements. This technique may have relevance in the field of proteomics that is used for innumerable applications. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Quantitative methods for studying design protocols

    CERN Document Server

    Kan, Jeff WT

    2017-01-01

    This book is aimed at researchers and students who would like to engage in and deepen their understanding of design cognition research. The book presents new approaches for analyzing design thinking and proposes methods of measuring design processes. These methods seek to quantify design issues and design processes that are defined based on notions from the Function-Behavior-Structure (FBS) design ontology and from linkography. A linkograph is a network of linked design moves or segments. FBS ontology concepts have been used in both design theory and design thinking research and have yielded numerous results. Linkography is one of the most influential and elegant design cognition research methods. In this book Kan and Gero provide novel and state-of-the-art methods of analyzing design protocols that offer insights into design cognition by integrating segmentation with linkography by assigning FBS-based codes to design moves or segments and treating links as FBS transformation processes. They propose and test ...

  11. A method for detecting hydrophobic patches protein

    NARCIS (Netherlands)

    Lijnzaad, P.; Berendsen, H.J.C.; Argos, P.

    1996-01-01

    A method for the detection of hydrophobic patches on the surfaces of protein tertiary structures is presented, it delineates explicit contiguous pieces of surface of arbitrary size and shape that consist solely of carbon and sulphur atoms using a dot representation of the solvent-accessible surface,

  12. Directory of Design Support Methods

    National Research Council Canada - National Science Library

    Dean, T

    1998-01-01

    This Directory contains records of human factors databases, handbooks, data guides, texts, journals, standardization documents, prototype and interface design tools, analytic techniques, and computer simulation software...

  13. Directory of Design Support Methods

    National Research Council Canada - National Science Library

    Dean, T

    1997-01-01

    This Directory contains records of human factors databases, handbooks, data guides, texts, journals, standardization documents, prototype and interface design tools, analytic techniques, and computer simulation software...

  14. Mechanical design of translocating motor proteins.

    Science.gov (United States)

    Hwang, Wonmuk; Lang, Matthew J

    2009-01-01

    Translocating motors generate force and move along a biofilament track to achieve diverse functions including gene transcription, translation, intracellular cargo transport, protein degradation, and muscle contraction. Advances in single molecule manipulation experiments, structural biology, and computational analysis are making it possible to consider common mechanical design principles of these diverse families of motors. Here, we propose a mechanical parts list that include track, energy conversion machinery, and moving parts. Energy is supplied not just by burning of a fuel molecule, but there are other sources or sinks of free energy, by binding and release of a fuel or products, or similarly between the motor and the track. Dynamic conformational changes of the motor domain can be regarded as controlling the flow of free energy to and from the surrounding heat reservoir. Multiple motor domains are organized in distinct ways to achieve motility under imposed physical constraints. Transcending amino acid sequence and structure, physically and functionally similar mechanical parts may have evolved as nature's design strategy for these molecular engines.

  15. Method for control-room display design

    International Nuclear Information System (INIS)

    Montmayeul, R.

    1988-01-01

    This document describes a method for control-room displays design. It can be used either for isolated display to add to an existing system either for the design of a full system of operator aids. The method is a top-down design with steps of possible iteration. The emphasis is put on display design rather than on system design; system aspects are just mentioned. Advantages of using a method are described [fr

  16. The Design Social: Framing social research methods for design postgraduates.

    OpenAIRE

    Evans, Martyn

    2010-01-01

    This paper discusses approaches for framing social research methods within postgraduate design curricula, details the responses of postgraduate design students to the possibilities presented by social research methods, and concludes with a case study of the adoption experiences of PhD students in design when engaging with social research methods. Analysis of semi-structured interviews is employed to draw out perceptions and experiences of design postgraduates when engaging with social researc...

  17. Design methods and design theory for architectural design management

    NARCIS (Netherlands)

    Achten, H.H.; Otter, den A.F.H.J.; Achten, H.H.; Pels, H.J.

    2008-01-01

    Most parties that an architectural design manager meets in daily practice are engaged to some degree with design. What these parties are actually doing in a project is contingent with the concrete design project. Additionally, each party has some stake, and may employ different strategies to solve

  18. Protein Structure Recognition: From Eigenvector Analysis to Structural Threading Method

    Energy Technology Data Exchange (ETDEWEB)

    Cao, Haibo [Iowa State Univ., Ames, IA (United States)

    2003-01-01

    In this work, they try to understand the protein folding problem using pair-wise hydrophobic interaction as the dominant interaction for the protein folding process. They found a strong correlation between amino acid sequences and the corresponding native structure of the protein. Some applications of this correlation were discussed in this dissertation include the domain partition and a new structural threading method as well as the performance of this method in the CASP5 competition. In the first part, they give a brief introduction to the protein folding problem. Some essential knowledge and progress from other research groups was discussed. This part includes discussions of interactions among amino acids residues, lattice HP model, and the design ability principle. In the second part, they try to establish the correlation between amino acid sequence and the corresponding native structure of the protein. This correlation was observed in the eigenvector study of protein contact matrix. They believe the correlation is universal, thus it can be used in automatic partition of protein structures into folding domains. In the third part, they discuss a threading method based on the correlation between amino acid sequences and ominant eigenvector of the structure contact-matrix. A mathematically straightforward iteration scheme provides a self-consistent optimum global sequence-structure alignment. The computational efficiency of this method makes it possible to search whole protein structure databases for structural homology without relying on sequence similarity. The sensitivity and specificity of this method is discussed, along with a case of blind test prediction. In the appendix, they list the overall performance of this threading method in CASP5 blind test in comparison with other existing approaches.

  19. Protein Structure Recognition: From Eigenvector Analysis to Structural Threading Method

    International Nuclear Information System (INIS)

    Haibo Cao

    2003-01-01

    In this work, they try to understand the protein folding problem using pair-wise hydrophobic interaction as the dominant interaction for the protein folding process. They found a strong correlation between amino acid sequences and the corresponding native structure of the protein. Some applications of this correlation were discussed in this dissertation include the domain partition and a new structural threading method as well as the performance of this method in the CASP5 competition. In the first part, they give a brief introduction to the protein folding problem. Some essential knowledge and progress from other research groups was discussed. This part includes discussions of interactions among amino acids residues, lattice HP model, and the design ability principle. In the second part, they try to establish the correlation between amino acid sequence and the corresponding native structure of the protein. This correlation was observed in the eigenvector study of protein contact matrix. They believe the correlation is universal, thus it can be used in automatic partition of protein structures into folding domains. In the third part, they discuss a threading method based on the correlation between amino acid sequences and ominant eigenvector of the structure contact-matrix. A mathematically straightforward iteration scheme provides a self-consistent optimum global sequence-structure alignment. The computational efficiency of this method makes it possible to search whole protein structure databases for structural homology without relying on sequence similarity. The sensitivity and specificity of this method is discussed, along with a case of blind test prediction. In the appendix, they list the overall performance of this threading method in CASP5 blind test in comparison with other existing approaches

  20. Computational design of proteins with novel structure and functions

    International Nuclear Information System (INIS)

    Yang Wei; Lai Lu-Hua

    2016-01-01

    Computational design of proteins is a relatively new field, where scientists search the enormous sequence space for sequences that can fold into desired structure and perform desired functions. With the computational approach, proteins can be designed, for example, as regulators of biological processes, novel enzymes, or as biotherapeutics. These approaches not only provide valuable information for understanding of sequence–structure–function relations in proteins, but also hold promise for applications to protein engineering and biomedical research. In this review, we briefly introduce the rationale for computational protein design, then summarize the recent progress in this field, including de novo protein design, enzyme design, and design of protein–protein interactions. Challenges and future prospects of this field are also discussed. (topical review)

  1. Design theory methods and organization for innovation

    CERN Document Server

    Le Masson, Pascal; Hatchuel, Armand

    2017-01-01

    This textbook presents the core of recent advances in design theory and its implications for design methods and design organization. Providing a unified perspective on different design methods and approaches, from the most classic (systematic design) to the most advanced (C-K theory), it offers a unique and integrated presentation of traditional and contemporary theories in the field. Examining the principles of each theory, this guide utilizes numerous real life industrial applications, with clear links to engineering design, industrial design, management, economics, psychology and creativity. Containing a section of exams with detailed answers, it is useful for courses in design theory, engineering design and advanced innovation management. "Students and professors, practitioners and researchers in diverse disciplines, interested in design, will find in this book a rich and vital source for studying fundamental design methods and tools as well as the most advanced design theories that work in practice". Pro...

  2. Prediction of Protein–Protein Interactions by Evidence Combining Methods

    Directory of Open Access Journals (Sweden)

    Ji-Wei Chang

    2016-11-01

    Full Text Available Most cellular functions involve proteins’ features based on their physical interactions with other partner proteins. Sketching a map of protein–protein interactions (PPIs is therefore an important inception step towards understanding the basics of cell functions. Several experimental techniques operating in vivo or in vitro have made significant contributions to screening a large number of protein interaction partners, especially high-throughput experimental methods. However, computational approaches for PPI predication supported by rapid accumulation of data generated from experimental techniques, 3D structure definitions, and genome sequencing have boosted the map sketching of PPIs. In this review, we shed light on in silico PPI prediction methods that integrate evidence from multiple sources, including evolutionary relationship, function annotation, sequence/structure features, network topology and text mining. These methods are developed for integration of multi-dimensional evidence, for designing the strategies to predict novel interactions, and for making the results consistent with the increase of prediction coverage and accuracy.

  3. Seismic design and analysis methods

    International Nuclear Information System (INIS)

    Varpasuo, P.

    1993-01-01

    Seismic load is in many areas of the world the most important loading situation from the point of view of structural strength. Taking this into account it is understandable, that there has been a strong allocation of resources in the seismic analysis during the past ten years. In this study there are three areas of the center of gravity: (1) Random vibrations; (2) Soil-structure interaction and (3) The methods for determining structural response. The solution of random vibration problems is clarified with the aid of applications in this study and from the point of view of mathematical treatment and mathematical formulations it is deemed sufficient to give the relevant sources. In the soil-structure interaction analysis the focus has been the significance of frequency dependent impedance functions. As a result it was obtained, that the description of the soil with the aid of frequency dependent impedance functions decreases the structural response and it is thus always the preferred method when compared to more conservative analysis types. From the methods to determine the C structural response the following four were tested: (1) The time history method; (2) The complex frequency-response method; (3) Response spectrum method and (4) The equivalent static force method. The time history appeared to be the most accurate method and the complex frequency-response method did have the widest area of application. (orig.). (14 refs., 35 figs.)

  4. Deep learning methods for protein torsion angle prediction.

    Science.gov (United States)

    Li, Haiou; Hou, Jie; Adhikari, Badri; Lyu, Qiang; Cheng, Jianlin

    2017-09-18

    Deep learning is one of the most powerful machine learning methods that has achieved the state-of-the-art performance in many domains. Since deep learning was introduced to the field of bioinformatics in 2012, it has achieved success in a number of areas such as protein residue-residue contact prediction, secondary structure prediction, and fold recognition. In this work, we developed deep learning methods to improve the prediction of torsion (dihedral) angles of proteins. We design four different deep learning architectures to predict protein torsion angles. The architectures including deep neural network (DNN) and deep restricted Boltzmann machine (DRBN), deep recurrent neural network (DRNN) and deep recurrent restricted Boltzmann machine (DReRBM) since the protein torsion angle prediction is a sequence related problem. In addition to existing protein features, two new features (predicted residue contact number and the error distribution of torsion angles extracted from sequence fragments) are used as input to each of the four deep learning architectures to predict phi and psi angles of protein backbone. The mean absolute error (MAE) of phi and psi angles predicted by DRNN, DReRBM, DRBM and DNN is about 20-21° and 29-30° on an independent dataset. The MAE of phi angle is comparable to the existing methods, but the MAE of psi angle is 29°, 2° lower than the existing methods. On the latest CASP12 targets, our methods also achieved the performance better than or comparable to a state-of-the art method. Our experiment demonstrates that deep learning is a valuable method for predicting protein torsion angles. The deep recurrent network architecture performs slightly better than deep feed-forward architecture, and the predicted residue contact number and the error distribution of torsion angles extracted from sequence fragments are useful features for improving prediction accuracy.

  5. Biomimetic design method for innovation and sustainability

    CERN Document Server

    Helfman Cohen, Yael

    2017-01-01

    Presenting a novel biomimetic design method for transferring design solutions from nature to technology, this book focuses on structure-function patterns in nature and advanced modeling tools derived from TRIZ, the theory of inventive problem-solving. The book includes an extensive literature review on biomimicry as an engine of both innovation and sustainability, and discusses in detail the biomimetic design process, current biomimetic design methods and tools. The structural biomimetic design method for innovation and sustainability put forward in this text encompasses (1) the research method and rationale used to develop and validate this new design method; (2) the suggested design algorithm and tools including the Findstructure database, structure-function patterns and ideality patterns; and (3) analyses of four case studies describing how to use the proposed method. This book offers an essential resource for designers who wish to use nature as a source of inspiration and knowledge, innovators and sustain...

  6. Methods and devices for protein assays

    Science.gov (United States)

    Chhabra, Swapnil [San Jose, CA; Cintron, Jose M [Indianapolis, IN; Shediac, Renee [Oakland, CA

    2009-11-03

    Methods and devices for protein assays based on Edman degradation in microfluidic channels are disclosed herein. As disclosed, the cleaved amino acid residues may be immobilized in an array format and identified by detectable labels, such as antibodies, which specifically bind given amino acid residues. Alternatively, the antibodies are immobilized in an array format and the cleaved amino acids are labeled identified by being bound by the antibodies in the array.

  7. A cookbook method for Persuasive Game Design

    Directory of Open Access Journals (Sweden)

    Panote Siriaraya

    2018-03-01

    Full Text Available Despite the growing interest in persuasive game design, there have been few methods which cover the complete process of game design that designers could draw upon in their practice. In this paper, the Persuasive Game Design method(PGD is presented as a non-directive approach for designing persuasive games including a practical hand-out. To better fit with the practical constraints encountered in game design, this method adopts a “cookbook” approach. A set of essential PGD components and tools are provided from which game designers can choose from, given their specific context and resources. Designers first consider the game design steps(“dishes” to use in creating their game and in each step, select which components(“ingredients” to take into account and tools(“utensils” to use. The proposed method, based on our experience as persuasive game researchers and design practitioners, is further refined using feedback from professional game designers. The paper concludes with a case study illustrating how to put the meal into practice. Overall, the method provides a useful contribution to the existing research domain by combining knowledge from game theory, game design and design methodology to create a structured yet flexible approach which covers the complete persuasive game design process for researchers, students and practitioners. 

  8. Design with the feet: walking methods and participatory design

    DEFF Research Database (Denmark)

    Kanstrup, Anne Marie; Bertelsen, Pernille; Madsen, Jacob Østergaard

    2014-01-01

    This paper presents an analysis of walking methods and their relation to participatory design (PD). The paper includes a study of walking methods found in the literature and an empirical study of transect walks in a PD project. From this analysis, we identify central attributes of, and challenges...... to, PD walks. Walking with people in the context of design is a natural activity for the participatory designer, who acknowledges the importance of immersion and relationships in design. However, the various intentions of walking approaches indicate an underacknowledged awareness of walking methods...

  9. Computational smart polymer design based on elastin protein mutability.

    Science.gov (United States)

    Tarakanova, Anna; Huang, Wenwen; Weiss, Anthony S; Kaplan, David L; Buehler, Markus J

    2017-05-01

    Soluble elastin-like peptides (ELPs) can be engineered into a range of physical forms, from hydrogels and scaffolds to fibers and artificial tissues, finding numerous applications in medicine and engineering as "smart polymers". Elastin-like peptides are attractive candidates as a platform for novel biomaterial design because they exhibit a highly tunable response spectrum, with reversible phase transition capabilities. Here, we report the design of the first virtual library of elastin-like protein models using methods for enhanced sampling to study the effect of peptide chemistry, chain length, and salt concentration on the structural transitions of ELPs, exposing associated molecular mechanisms. We describe the behavior of the local molecular structure under increasing temperatures and the effect of peptide interactions with nearest hydration shell water molecules on peptide mobility and propensity to exhibit structural transitions. Shifts in the magnitude of structural transitions at the single-molecule scale are explained from the perspective of peptide-ion-water interactions in a library of four unique elastin-like peptide systems. Predictions of structural transitions are subsequently validated in experiment. This library is a valuable resource for recombinant protein design and synthesis as it elucidates mechanisms at the single-molecule level, paving a feedback path between simulation and experiment for smart material designs, with applications in biomedicine and diagnostic devices. Copyright © 2017. Published by Elsevier Ltd.

  10. Design methods as discourse on practice

    DEFF Research Database (Denmark)

    Cohn, Marisa

    2010-01-01

    In this paper, we present a view of design methods as discourse on practice. We consider how the deployment of a particular set of design methods enables and constrains not only practical action but also discursive action within the design practice. A case study of agile software development meth...... of practices. We then discuss implications of this view on methods for CSCW research on the relationship between methods and practice as well as implications for participation in the design process.......In this paper, we present a view of design methods as discourse on practice. We consider how the deployment of a particular set of design methods enables and constrains not only practical action but also discursive action within the design practice. A case study of agile software development...... methods illustrates the ways that methods establish conditions for who can speak in the design process and how. We indentify three main kinds of discourse work performed in the invoking of design methods. These are the establishing of ontologies, the authorizing of voices, and the legitimizing...

  11. Design, properties, and applications of protein micro- and nanoparticles

    NARCIS (Netherlands)

    Saglam, Dilek; Venema, Paul; van der Linden, Erik; de Vries, Renko

    2014-01-01

    The design of protein particles with tailored properties has received an increased attention recently. Several approaches, from simple heat treatment in dilute systems to the combination of heat and mechanical treatments in concentrated protein solutions, have been used to obtain protein particles

  12. Teaching Healthcare Design. Methods for Empathy

    DEFF Research Database (Denmark)

    Dankl, Kathrina

    2017-01-01

    discussed in design. By evidence of a design course focusing on shared decision making (SDM), this paper promotes a blended set of methods, supporting enhanced understanding amongst stakeholders. The empirical data and the comparison with contemporary SDM studies indicate that student designers were able......Healthcare design requires empathetic understanding among all stakeholders and consequently the development of design for empathy. While design anthropological approaches are broadly discussed, spanning from social design to social innovation, analysis methods for human insights are less widely...... to address some of the most vividly discussed issues in the field: the adaption of SDM to the diversity of patients, the flow of information between the different stakeholders and the general knowledge on SDM by clinicians and the wider public. This paper provides design educators with a series of methods...

  13. Rational Design of Rho Protein Inhibitors

    National Research Council Canada - National Science Library

    Rojas, Rafael J

    2006-01-01

    Rho GTPases are molecular switches that fluctuate between on and off states. When active, these proteins function to remodel the actin cytoskeleton by interacting with a number of downstream effector molecules...

  14. Rational Design of Rho Protein Inhibitors

    National Research Council Canada - National Science Library

    Rojas, Rafael J

    2005-01-01

    Rho GTPases are molecular switches that fluctuate between on and off states. When active, these proteins function to remodel the actin cytoskeleton by interacting with a number of downstream effector molecules...

  15. General method for designing wave shape transformers.

    Science.gov (United States)

    Ma, Hua; Qu, Shaobo; Xu, Zhuo; Wang, Jiafu

    2008-12-22

    An effective method for designing wave shape transformers (WSTs) is investigated by adopting the coordinate transformation theory. Following this method, the devices employed to transform electromagnetic (EM) wave fronts from one style with arbitrary shape and size to another style, can be designed. To verify this method, three examples in 2D spaces are also presented. Compared with the methods proposed in other literatures, this method offers the general procedure in designing WSTs, and thus is of great importance for the potential and practical applications possessed by such kinds of devices.

  16. Protocol design and implementation using formal methods

    NARCIS (Netherlands)

    van Sinderen, Marten J.; Ferreira Pires, Luis; Pires, L.F.; Vissers, C.A.

    1992-01-01

    This paper reports on a number of formal methods that support correct protocol design and implementation. These methods are placed in the framework of a design methodology for distributed systems that was studied and developed within the ESPRIT II Lotosphere project (2304). The paper focuses on

  17. HTGR analytical methods and design verification

    International Nuclear Information System (INIS)

    Neylan, A.J.; Northup, T.E.

    1982-05-01

    Analytical methods for the high-temperature gas-cooled reactor (HTGR) include development, update, verification, documentation, and maintenance of all computer codes for HTGR design and analysis. This paper presents selected nuclear, structural mechanics, seismic, and systems analytical methods related to the HTGR core. This paper also reviews design verification tests in the reactor core, reactor internals, steam generator, and thermal barrier

  18. Smarter Drugs: How Protein Crystallography Revolutionizes Drug Design

    International Nuclear Information System (INIS)

    Smith, Clyde

    2005-01-01

    According to Smith, protein crystallography allows scientists to design drugs in a much more efficient way than the standard methods traditionally used by large drug companies, which can cost close to a billion dollars and take 10 to 15 years. 'A lot of the work can be compressed down,' Smith said. Protein crystallography enables researchers to learn the structure of molecules involved in disease and health. Seeing the loops, folds and placement of atoms in anything from a virus to a healthy cell membrane gives important information about how these things work - and how to encourage, sidestep or stop their functions. Drug design can be much faster when the relationship between structure and function tells you what area of a molecule to target. Smith will use a timeline to illustrate the traditional methods of drug development and the new ways it can be done now. 'It is very exciting work. There have been some failures, but many successes too.' A new drug to combat the flu was developed in a year or so. Smith will tell us how. He will also highlight drugs developed to combat HIV, Tuberculosis, hypertension and Anthrax.

  19. Towards the nonstick egg: designing fluorous proteins.

    Science.gov (United States)

    Neil, E; Marsh, G

    2000-07-01

    Anyone who has made scrambled eggs will have had cause to praise the properties of Teflon. Teflon's highly chemically inert and nonstick nature derives from the perfluorinated polymer polytetrafluoroethylene. Perfluorocarbons have unique and valuable physical properties not found in nature. By incorporating fluorine into proteins, it might be possible to produce biological molecules with novel and useful properties.

  20. Design and functionality of dense protein particles

    NARCIS (Netherlands)

    Saglam, D.

    2012-01-01

    Food products that contain high levels of protein can help to control food intake and to maintain a healthy body weight due to their strong satiating properties. They are also beneficial in the nutrition of elderly and commonly used in medical nutrition. Preparation of food products at high

  1. Culture, Interface Design, and Design Methods for Mobile Devices

    Science.gov (United States)

    Lee, Kun-Pyo

    Aesthetic differences and similarities among cultures are obviously one of the very important issues in cultural design. However, ever since products became knowledge-supporting tools, the visible elements of products have become more universal so that the invisible parts of products such as interface and interaction are getting more important. Therefore, the cultural design should be extended to the invisible elements of culture like people's conceptual models beyond material and phenomenal culture. This chapter aims to explain how we address the invisible cultural elements in interface design and design methods by exploring the users' cognitive styles and communication patterns in different cultures. Regarding cultural interface design, we examined users' conceptual models while interacting with mobile phone and website interfaces, and observed cultural difference in performing tasks and viewing patterns, which appeared to agree with cultural cognitive styles known as Holistic thoughts vs. Analytic thoughts. Regarding design methods for culture, we explored how to localize design methods such as focus group interview and generative session for specific cultural groups, and the results of comparative experiments revealed cultural difference on participants' behaviors and performance in each design method and led us to suggest how to conduct them in East Asian culture. Mobile Observation Analyzer and Wi-Pro, user research tools we invented to capture user behaviors and needs especially in their mobile context, were also introduced.

  2. Rationally designed synthetic protein hydrogels with predictable mechanical properties.

    Science.gov (United States)

    Wu, Junhua; Li, Pengfei; Dong, Chenling; Jiang, Heting; Bin Xue; Gao, Xiang; Qin, Meng; Wang, Wei; Bin Chen; Cao, Yi

    2018-02-12

    Designing synthetic protein hydrogels with tailored mechanical properties similar to naturally occurring tissues is an eternal pursuit in tissue engineering and stem cell and cancer research. However, it remains challenging to correlate the mechanical properties of protein hydrogels with the nanomechanics of individual building blocks. Here we use single-molecule force spectroscopy, protein engineering and theoretical modeling to prove that the mechanical properties of protein hydrogels are predictable based on the mechanical hierarchy of the cross-linkers and the load-bearing modules at the molecular level. These findings provide a framework for rationally designing protein hydrogels with independently tunable elasticity, extensibility, toughness and self-healing. Using this principle, we demonstrate the engineering of self-healable muscle-mimicking hydrogels that can significantly dissipate energy through protein unfolding. We expect that this principle can be generalized for the construction of protein hydrogels with customized mechanical properties for biomedical applications.

  3. Participatory design methods in telemedicine research

    DEFF Research Database (Denmark)

    Danbjørg, Dorthe Boe; Clemensen, Jane; Rothmann, Mette Juel

    together with the patients. Participatory design is a research design and methodology that encourages the participation of users in the design process of technological solutions. Therefore, it has a potential for designing technologies that actually reflect the needs of the users, why it is relevant within...... telemedicine. The aim of this presentation is to explain the process and theoretical framework of a PD project; give an example of a project including the applied methods, and to determine its application to telemedicine with focus on the rationale for genuine participation. Theory: Participation implies....... Methods: Key activities of a Participatory Design project comprise methods such as fieldwork; literature reviewing; development and testing, and user activities as workshops. Methods that support telling, making, enacting. For instance telling activities as drivers for participation, where practitioners...

  4. Fast computational methods for predicting protein structure from primary amino acid sequence

    Science.gov (United States)

    Agarwal, Pratul Kumar [Knoxville, TN

    2011-07-19

    The present invention provides a method utilizing primary amino acid sequence of a protein, energy minimization, molecular dynamics and protein vibrational modes to predict three-dimensional structure of a protein. The present invention also determines possible intermediates in the protein folding pathway. The present invention has important applications to the design of novel drugs as well as protein engineering. The present invention predicts the three-dimensional structure of a protein independent of size of the protein, overcoming a significant limitation in the prior art.

  5. Drafting method of electricity and electron design

    International Nuclear Information System (INIS)

    Gungbon, Junchun

    1989-11-01

    This book concentrates on drafting of electricity and electron design. It deals with The meaning of electricity and electron drafting JIS standard regulation the types of drafting and line and letter, basics drafting with projection drafting method, plan projection and development elevation, Drafting method of shop drawing, practical method of design and drafting, Design and drafting of technic and illustration, Connection diagram, Drafting of wiring diagram for light and illumination, Drafting of development connection diagram for sequence control, Drafting of logic circuit sign of flow chart and manual, drafting for a electron circuit diagram and Drawing of PC board.

  6. Characterization of redox proteins using electrochemical methods

    OpenAIRE

    Verhagen, M.

    1995-01-01

    The use of electrochemical techniques in combination with proteins started approximately a decade ago and has since then developed into a powerfull technique for the study of small redox proteins. In addition to the determination of redox potentials, electrochemistry can be used to obtain information about the kinetics of electron transfer between proteins and about the dynamic behaviour of redox cofactors in proteins. This thesis describes the results of a study, initiated to get a ...

  7. Method Usage in Design : How methods function as mental tools for designers

    NARCIS (Netherlands)

    Daalhuizen, J.J.

    2014-01-01

    Methods are means to help designers achieve desired change as efficiently and effectively as possible. Methods can be used to do so in the context of learning - to help teach students how to design on a professional level. Methods can also be used in the context of performance - to help designers

  8. Design of a hyperstable 60-subunit protein icosahedron

    Science.gov (United States)

    Hsia, Yang; Bale, Jacob B.; Gonen, Shane; Shi, Dan; Sheffler, William; Fong, Kimberly K.; Nattermann, Una; Xu, Chunfu; Huang, Po-Ssu; Ravichandran, Rashmi; Yi, Sue; Davis, Trisha N.; Gonen, Tamir; King, Neil P.; Baker, David

    2016-07-01

    The icosahedron is the largest of the Platonic solids, and icosahedral protein structures are widely used in biological systems for packaging and transport. There has been considerable interest in repurposing such structures for applications ranging from targeted delivery to multivalent immunogen presentation. The ability to design proteins that self-assemble into precisely specified, highly ordered icosahedral structures would open the door to a new generation of protein containers with properties custom-tailored to specific applications. Here we describe the computational design of a 25-nanometre icosahedral nanocage that self-assembles from trimeric protein building blocks. The designed protein was produced in Escherichia coli, and found by electron microscopy to assemble into a homogenous population of icosahedral particles nearly identical to the design model. The particles are stable in 6.7 molar guanidine hydrochloride at up to 80 degrees Celsius, and undergo extremely abrupt, but reversible, disassembly between 2 molar and 2.25 molar guanidinium thiocyanate. The icosahedron is robust to genetic fusions: one or two copies of green fluorescent protein (GFP) can be fused to each of the 60 subunits to create highly fluorescent ‘standard candles’ for use in light microscopy, and a designed protein pentamer can be placed in the centre of each of the 20 pentameric faces to modulate the size of the entrance/exit channels of the cage. Such robust and customizable nanocages should have considerable utility in targeted drug delivery, vaccine design and synthetic biology.

  9. Phenomenological Research Method, Design and Procedure: A ...

    African Journals Online (AJOL)

    Phenomenological Research Method, Design and Procedure: A Phenomenological Investigation of the Phenomenon of Being-in-Community as Experienced by Two Individuals Who Have Participated in a Community Building Workshop.

  10. Development of New Bituminous Pavement Design Method

    DEFF Research Database (Denmark)

    Ullidtz, Per

    The report and work of COST Action 333 sets in place the foundation for a coherent, cost-effective and harmonised European pavement design method. In order to do this, the work programme focused on information gathering, identification of requirements and the selection of the necessary design...

  11. Revision of South African pavement design method

    CSIR Research Space (South Africa)

    Kannemeyer, L

    2015-08-01

    Full Text Available an improved mechanistic-empirical design method has been developed, based on the latest available local and international research and design trends. The process followed during revision as well as some of the key outcomes of this process are presented...

  12. Comparing early design methods for children

    NARCIS (Netherlands)

    Sluis - Thiescheffer, R.J.W.; Bekker, M.M.; Eggen, J.H.; Robertson, J.; Skov, M.B.; Bekker, M.M.

    2007-01-01

    This paper describes a study which compares the outcome of two early design methods for children: brainstorming and prototyping. The hypothesis is that children will uncover more design ideas when prototyping than when brainstorming, because prototyping requires the use of a wider range of

  13. Mixed Methods Research Designs in Counseling Psychology

    Science.gov (United States)

    Hanson, William E.; Creswell, John W.; Clark, Vicki L. Plano; Petska, Kelly S.; Creswell, David J.

    2005-01-01

    With the increased popularity of qualitative research, researchers in counseling psychology are expanding their methodologies to include mixed methods designs. These designs involve the collection, analysis, and integration of quantitative and qualitative data in a single or multiphase study. This article presents an overview of mixed methods…

  14. Design methods in solid rocket motors

    Energy Technology Data Exchange (ETDEWEB)

    1987-03-01

    A compilation of lectures summarizing the current state-of-the-art in designing solid rocket motors and and their components is presented. The experience of several countries in the use of new technologies and methods is represented. Specific sessions address propellant grains, cases, nozzles, internal thermal insulation, and the general optimization of solid rocket motor designs.

  15. Concurrent semantics for structured design methods

    OpenAIRE

    Nixon, Patrick

    1996-01-01

    Also in Jelly, I., Gordon, I., & Groll, P. Software Engineering for Parallel and Distributed Systems. London: Chapman Hall. Design methods can be ambiguous due to di#11;erent interpretations of symbols or concepts. This paper presents a formal semantics for the Ward/Mellor Structured Analysis Method for Real Time systems. These semantics ensures that an unambiguous meaning can be attributed to a particular design. Speci#12;cally, it ensures that concurrent and real-time propert...

  16. Assessing the Accuracy of Ancestral Protein Reconstruction Methods

    OpenAIRE

    Williams, Paul D; Pollock, David D; Blackburne, Benjamin P; Goldstein, Richard A

    2006-01-01

    The phylogenetic inference of ancestral protein sequences is a powerful technique for the study of molecular evolution, but any conclusions drawn from such studies are only as good as the accuracy of the reconstruction method. Every inference method leads to errors in the ancestral protein sequence, resulting in potentially misleading estimates of the ancestral protein's properties. To assess the accuracy of ancestral protein reconstruction methods, we performed computational population evolu...

  17. Cost Function Network-based Design of Protein-Protein Interactions: predicting changes in binding affinity.

    Science.gov (United States)

    Viricel, Clément; de Givry, Simon; Schiex, Thomas; Barbe, Sophie

    2018-02-20

    Accurate and economic methods to predict change in protein binding free energy upon mutation are imperative to accelerate the design of proteins for a wide range of applications. Free energy is defined by enthalpic and entropic contributions. Following the recent progresses of Artificial Intelligence-based algorithms for guaranteed NP-hard energy optimization and partition function computation, it becomes possible to quickly compute minimum energy conformations and to reliably estimate the entropic contribution of side-chains in the change of free energy of large protein interfaces. Using guaranteed Cost Function Network algorithms, Rosetta energy functions and Dunbrack's rotamer library, we developed and assessed EasyE and JayZ, two methods for binding affinity estimation that ignore or include conformational entropic contributions on a large benchmark of binding affinity experimental measures. If both approaches outperform most established tools, we observe that side-chain conformational entropy brings little or no improvement on most systems but becomes crucial in some rare cases. as open-source Python/C ++ code at sourcesup.renater.fr/projects/easy-jayz. thomas.schiex@inra.fr and sophie.barbe@insa-toulouse.fr. Supplementary data are available at Bioinformatics online.

  18. Mechatronic Systems Design Methods, Models, Concepts

    CERN Document Server

    Janschek, Klaus

    2012-01-01

    In this textbook, fundamental methods for model-based design of mechatronic systems are presented in a systematic, comprehensive form. The method framework presented here comprises domain-neutral methods for modeling and performance analysis: multi-domain modeling (energy/port/signal-based), simulation (ODE/DAE/hybrid systems), robust control methods, stochastic dynamic analysis, and quantitative evaluation of designs using system budgets. The model framework is composed of analytical dynamic models for important physical and technical domains of realization of mechatronic functions, such as multibody dynamics, digital information processing and electromechanical transducers. Building on the modeling concept of a technology-independent generic mechatronic transducer, concrete formulations for electrostatic, piezoelectric, electromagnetic, and electrodynamic transducers are presented. More than 50 fully worked out design examples clearly illustrate these methods and concepts and enable independent study of th...

  19. Refolding of proteins from inclusion bodies: rational design and recipes.

    Science.gov (United States)

    Basu, Anindya; Li, Xiang; Leong, Susanna Su Jan

    2011-10-01

    The need to develop protein biomanufacturing platforms that can deliver proteins quickly and cost-effectively is ever more pressing. The rapid rate at which genomes can now be sequenced demands efficient protein production platforms for gene function identification. There is a continued need for the biotech industry to deliver new and more effective protein-based drugs to address new diseases. Bacterial production platforms have the advantage of high expression yields, but insoluble expression of many proteins necessitates the development of diverse and optimised refolding-based processes. Strategies employed to eliminate insoluble expression are reviewed, where it is concluded that inclusion bodies are difficult to eliminate for various reasons. Rational design of refolding systems and recipes are therefore needed to expedite production of recombinant proteins. This review article discusses efforts towards rational design of refolding systems and recipes, which can be guided by the development of refolding screening platforms that yield both qualitative and quantitative information on the progression of a given refolding process. The new opportunities presented by light scattering technologies for developing rational protein refolding buffer systems which in turn can be used to develop new process designs armed with better monitoring and controlling functionalities are discussed. The coupling of dynamic and static light scattering methodologies for incorporation into future bioprocess designs to ensure delivery of high-quality refolded proteins at faster rates is also discussed.

  20. Use of designed sequences in protein structure recognition.

    Science.gov (United States)

    Kumar, Gayatri; Mudgal, Richa; Srinivasan, Narayanaswamy; Sandhya, Sankaran

    2018-05-09

    Knowledge of the protein structure is a pre-requisite for improved understanding of molecular function. The gap in the sequence-structure space has increased in the post-genomic era. Grouping related protein sequences into families can aid in narrowing the gap. In the Pfam database, structure description is provided for part or full-length proteins of 7726 families. For the remaining 52% of the families, information on 3-D structure is not yet available. We use the computationally designed sequences that are intermediately related to two protein domain families, which are already known to share the same fold. These strategically designed sequences enable detection of distant relationships and here, we have employed them for the purpose of structure recognition of protein families of yet unknown structure. We first measured the success rate of our approach using a dataset of protein families of known fold and achieved a success rate of 88%. Next, for 1392 families of yet unknown structure, we made structural assignments for part/full length of the proteins. Fold association for 423 domains of unknown function (DUFs) are provided as a step towards functional annotation. The results indicate that knowledge-based filling of gaps in protein sequence space is a lucrative approach for structure recognition. Such sequences assist in traversal through protein sequence space and effectively function as 'linkers', where natural linkers between distant proteins are unavailable. This article was reviewed by Oliviero Carugo, Christine Orengo and Srikrishna Subramanian.

  1. Problem Solving Methods in Engineering Design

    DEFF Research Database (Denmark)

    Hartvig, Susanne C

    1999-01-01

    This short paper discusses typical engineering tasks and problem solving methods, based on a field study of engineering tasks at a Danish engineering firm. The field study has identified ten classes of design tasks and in this paper these classes are related to problem solving methods. The descri...

  2. Methods for production of proteins in host cells

    Science.gov (United States)

    Donnelly, Mark; Joachimiak, Andrzej

    2004-01-13

    The present invention provides methods for the production of proteins, particularly toxic proteins, in host cells. The invention provides methods which use a fusion protein comprising a chaperonin binding domain in host cells induced or regulated to have increased levels of chaperonin which binds the chaperonin binding domain.

  3. Photoswitchable method for the ordered attachment of proteins to surfaces

    Science.gov (United States)

    Camarero, Julio A.; De Yoreo, James J.; Kwon, Youngeun

    2010-04-20

    Described herein is a method for the attachment of proteins to any solid support with control over the orientation of the attachment. The method is extremely efficient, not requiring the previous purification of the protein to be attached, and can be activated by UV-light. Spatially addressable arrays of multiple protein components can be generated by using standard photolithographic techniques.

  4. Photoswitchable method for the ordered attachment of proteins to surfaces

    Science.gov (United States)

    Camarero, Julio A [Livermore, CA; DeYoreo, James J [Clayton, CA; Kwon, Youngeun [Livermore, CA

    2011-07-05

    Described herein is a method for the attachment of proteins to any solid support with control over the orientation of the attachment. The method is extremely efficient, not requiring the previous purification of the protein to be attached, and can be activated by UV-light. Spatially addressable arrays of multiple protein components can be generated by using standard photolithographic techniques.

  5. Potency assay design for adjuvanted recombinant proteins as malaria vaccines.

    Science.gov (United States)

    Giersing, Birgitte K; Dubovsky, Filip; Saul, Allan; Denamur, Francoise; Minor, Philip; Meade, Bruce

    2006-05-15

    Many licensed vaccines are composed of live, attenuated or inactivated whole-cell microorganisms, or they comprise purified components from whole-cell extracts or culture supernatants. For some diseases, pathology is fairly well understood, and there may be known correlates of protection that provide obvious parameters for assessment of vaccine potency. However, this is not always the case, and some effective vaccines are routinely used even though the mechanisms or correlates of protection are unknown. Some more modern vaccine approaches employ purified recombinant proteins, based on molecules that appear on the surface of the pathogen. This is one of the strategies that has been adopted in the quest to develop a malaria vaccine. Use of these parasite antigens as vaccine candidates is supported by substantial epidemiological data, and some have demonstrated the ability to elicit protective responses in animal models of malaria infection. However, there is as yet no immunological correlate of protection and no functional assays or animal models that have demonstrated the ability to predict efficacy in humans. There is little precedence for the most appropriate and practical method for assessing potency of vaccines based on these recombinant molecules for malaria vaccines. This is likely because the majority of malaria vaccine candidates have only recently entered clinical evaluation. The PATH Malaria Vaccine Initiative (MVI) convened a panel with expertise in potency assay design from industry, governmental institutions, and regulatory bodies to discuss and review the rationale, available methods, and best approaches for assessing the potency of recombinant proteins, specifically for their use as malarial vaccines. The aim of this meeting was to produce a discussion document on the practical potency assessment of recombinant protein malaria vaccines, focusing on early phase potency assay development.

  6. Monte Carlo methods for shield design calculations

    International Nuclear Information System (INIS)

    Grimstone, M.J.

    1974-01-01

    A suite of Monte Carlo codes is being developed for use on a routine basis in commercial reactor shield design. The methods adopted for this purpose include the modular construction of codes, simplified geometries, automatic variance reduction techniques, continuous energy treatment of cross section data, and albedo methods for streaming. Descriptions are given of the implementation of these methods and of their use in practical calculations. 26 references. (U.S.)

  7. Characterization of redox proteins using electrochemical methods

    NARCIS (Netherlands)

    Verhagen, M.

    1995-01-01

    The use of electrochemical techniques in combination with proteins started approximately a decade ago and has since then developed into a powerfull technique for the study of small redox proteins. In addition to the determination of redox potentials, electrochemistry can be used to obtain

  8. The architectural design of networks of protein domain architectures.

    Science.gov (United States)

    Hsu, Chia-Hsin; Chen, Chien-Kuo; Hwang, Ming-Jing

    2013-08-23

    Protein domain architectures (PDAs), in which single domains are linked to form multiple-domain proteins, are a major molecular form used by evolution for the diversification of protein functions. However, the design principles of PDAs remain largely uninvestigated. In this study, we constructed networks to connect domain architectures that had grown out from the same single domain for every single domain in the Pfam-A database and found that there are three main distinctive types of these networks, which suggests that evolution can exploit PDAs in three different ways. Further analysis showed that these three different types of PDA networks are each adopted by different types of protein domains, although many networks exhibit the characteristics of more than one of the three types. Our results shed light on nature's blueprint for protein architecture and provide a framework for understanding architectural design from a network perspective.

  9. A Signal Processing Method to Explore Similarity in Protein Flexibility

    Directory of Open Access Journals (Sweden)

    Simina Vasilache

    2010-01-01

    Full Text Available Understanding mechanisms of protein flexibility is of great importance to structural biology. The ability to detect similarities between proteins and their patterns is vital in discovering new information about unknown protein functions. A Distance Constraint Model (DCM provides a means to generate a variety of flexibility measures based on a given protein structure. Although information about mechanical properties of flexibility is critical for understanding protein function for a given protein, the question of whether certain characteristics are shared across homologous proteins is difficult to assess. For a proper assessment, a quantified measure of similarity is necessary. This paper begins to explore image processing techniques to quantify similarities in signals and images that characterize protein flexibility. The dataset considered here consists of three different families of proteins, with three proteins in each family. The similarities and differences found within flexibility measures across homologous proteins do not align with sequence-based evolutionary methods.

  10. An Integrated Framework Advancing Membrane Protein Modeling and Design.

    Directory of Open Access Journals (Sweden)

    Rebecca F Alford

    2015-09-01

    Full Text Available Membrane proteins are critical functional molecules in the human body, constituting more than 30% of open reading frames in the human genome. Unfortunately, a myriad of difficulties in overexpression and reconstitution into membrane mimetics severely limit our ability to determine their structures. Computational tools are therefore instrumental to membrane protein structure prediction, consequently increasing our understanding of membrane protein function and their role in disease. Here, we describe a general framework facilitating membrane protein modeling and design that combines the scientific principles for membrane protein modeling with the flexible software architecture of Rosetta3. This new framework, called RosettaMP, provides a general membrane representation that interfaces with scoring, conformational sampling, and mutation routines that can be easily combined to create new protocols. To demonstrate the capabilities of this implementation, we developed four proof-of-concept applications for (1 prediction of free energy changes upon mutation; (2 high-resolution structural refinement; (3 protein-protein docking; and (4 assembly of symmetric protein complexes, all in the membrane environment. Preliminary data show that these algorithms can produce meaningful scores and structures. The data also suggest needed improvements to both sampling routines and score functions. Importantly, the applications collectively demonstrate the potential of combining the flexible nature of RosettaMP with the power of Rosetta algorithms to facilitate membrane protein modeling and design.

  11. OSPREY: protein design with ensembles, flexibility, and provable algorithms.

    Science.gov (United States)

    Gainza, Pablo; Roberts, Kyle E; Georgiev, Ivelin; Lilien, Ryan H; Keedy, Daniel A; Chen, Cheng-Yu; Reza, Faisal; Anderson, Amy C; Richardson, David C; Richardson, Jane S; Donald, Bruce R

    2013-01-01

    We have developed a suite of protein redesign algorithms that improves realistic in silico modeling of proteins. These algorithms are based on three characteristics that make them unique: (1) improved flexibility of the protein backbone, protein side-chains, and ligand to accurately capture the conformational changes that are induced by mutations to the protein sequence; (2) modeling of proteins and ligands as ensembles of low-energy structures to better approximate binding affinity; and (3) a globally optimal protein design search, guaranteeing that the computational predictions are optimal with respect to the input model. Here, we illustrate the importance of these three characteristics. We then describe OSPREY, a protein redesign suite that implements our protein design algorithms. OSPREY has been used prospectively, with experimental validation, in several biomedically relevant settings. We show in detail how OSPREY has been used to predict resistance mutations and explain why improved flexibility, ensembles, and provability are essential for this application. OSPREY is free and open source under a Lesser GPL license. The latest version is OSPREY 2.0. The program, user manual, and source code are available at www.cs.duke.edu/donaldlab/software.php. osprey@cs.duke.edu. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Novel Methods for Electromagnetic Simulation and Design

    Science.gov (United States)

    2016-08-03

    modeling software that can handle complicated, electrically large objects in a manner that is sufficiently fast to allow design by simulation. 15. SUBJECT...electrically large objects in a manner that is sufficiently fast to allow design by simulation. We also developed new methods for scattering from cavities in a...basis for high fidelity modeling software that can handle complicated, electrically large objects in a manner that is sufficiently fast to allow

  13. Efficient protein structure search using indexing methods.

    Science.gov (United States)

    Kim, Sungchul; Sael, Lee; Yu, Hwanjo

    2013-01-01

    Understanding functions of proteins is one of the most important challenges in many studies of biological processes. The function of a protein can be predicted by analyzing the functions of structurally similar proteins, thus finding structurally similar proteins accurately and efficiently from a large set of proteins is crucial. A protein structure can be represented as a vector by 3D-Zernike Descriptor (3DZD) which compactly represents the surface shape of the protein tertiary structure. This simplified representation accelerates the searching process. However, computing the similarity of two protein structures is still computationally expensive, thus it is hard to efficiently process many simultaneous requests of structurally similar protein search. This paper proposes indexing techniques which substantially reduce the search time to find structurally similar proteins. In particular, we first exploit two indexing techniques, i.e., iDistance and iKernel, on the 3DZDs. After that, we extend the techniques to further improve the search speed for protein structures. The extended indexing techniques build and utilize an reduced index constructed from the first few attributes of 3DZDs of protein structures. To retrieve top-k similar structures, top-10 × k similar structures are first found using the reduced index, and top-k structures are selected among them. We also modify the indexing techniques to support θ-based nearest neighbor search, which returns data points less than θ to the query point. The results show that both iDistance and iKernel significantly enhance the searching speed. In top-k nearest neighbor search, the searching time is reduced 69.6%, 77%, 77.4% and 87.9%, respectively using iDistance, iKernel, the extended iDistance, and the extended iKernel. In θ-based nearest neighbor serach, the searching time is reduced 80%, 81%, 95.6% and 95.6% using iDistance, iKernel, the extended iDistance, and the extended iKernel, respectively.

  14. Applications of Protein Thermodynamic Database for Understanding Protein Mutant Stability and Designing Stable Mutants.

    Science.gov (United States)

    Gromiha, M Michael; Anoosha, P; Huang, Liang-Tsung

    2016-01-01

    Protein stability is the free energy difference between unfolded and folded states of a protein, which lies in the range of 5-25 kcal/mol. Experimentally, protein stability is measured with circular dichroism, differential scanning calorimetry, and fluorescence spectroscopy using thermal and denaturant denaturation methods. These experimental data have been accumulated in the form of a database, ProTherm, thermodynamic database for proteins and mutants. It also contains sequence and structure information of a protein, experimental methods and conditions, and literature information. Different features such as search, display, and sorting options and visualization tools have been incorporated in the database. ProTherm is a valuable resource for understanding/predicting the stability of proteins and it can be accessed at http://www.abren.net/protherm/ . ProTherm has been effectively used to examine the relationship among thermodynamics, structure, and function of proteins. We describe the recent progress on the development of methods for understanding/predicting protein stability, such as (1) general trends on mutational effects on stability, (2) relationship between the stability of protein mutants and amino acid properties, (3) applications of protein three-dimensional structures for predicting their stability upon point mutations, (4) prediction of protein stability upon single mutations from amino acid sequence, and (5) prediction methods for addressing double mutants. A list of online resources for predicting has also been provided.

  15. Design of heat exchangers by numerical methods

    International Nuclear Information System (INIS)

    Konuk, A.A.

    1981-01-01

    Differential equations describing the heat tranfer in shell - and tube heat exchangers are derived and solved numerically. The method of ΔT sub(lm) is compared with the proposed method in cases where the specific heat at constant pressure, Cp and the overall heat transfer coefficient, U, vary with temperature. The error of the method of ΔT sub (lm) for the computation of the exchanger lenght is less than + 10%. However, the numerical method, being more accurate and at the same time easy to use and economical, is recommended for the design of shell-and-tube heat exchangers. (Author) [pt

  16. Optimization methods applied to hybrid vehicle design

    Science.gov (United States)

    Donoghue, J. F.; Burghart, J. H.

    1983-01-01

    The use of optimization methods as an effective design tool in the design of hybrid vehicle propulsion systems is demonstrated. Optimization techniques were used to select values for three design parameters (battery weight, heat engine power rating and power split between the two on-board energy sources) such that various measures of vehicle performance (acquisition cost, life cycle cost and petroleum consumption) were optimized. The apporach produced designs which were often significant improvements over hybrid designs already reported on in the literature. The principal conclusions are as follows. First, it was found that the strategy used to split the required power between the two on-board energy sources can have a significant effect on life cycle cost and petroleum consumption. Second, the optimization program should be constructed so that performance measures and design variables can be easily changed. Third, the vehicle simulation program has a significant effect on the computer run time of the overall optimization program; run time can be significantly reduced by proper design of the types of trips the vehicle takes in a one year period. Fourth, care must be taken in designing the cost and constraint expressions which are used in the optimization so that they are relatively smooth functions of the design variables. Fifth, proper handling of constraints on battery weight and heat engine rating, variables which must be large enough to meet power demands, is particularly important for the success of an optimization study. Finally, the principal conclusion is that optimization methods provide a practical tool for carrying out the design of a hybrid vehicle propulsion system.

  17. Design of multi-specificity in protein interfaces.

    Directory of Open Access Journals (Sweden)

    Elisabeth L Humphris

    2007-08-01

    Full Text Available Interactions in protein networks may place constraints on protein interface sequences to maintain correct and avoid unwanted interactions. Here we describe a "multi-constraint" protein design protocol to predict sequences optimized for multiple criteria, such as maintaining sets of interactions, and apply it to characterize the mechanism and extent to which 20 multi-specific proteins are constrained by binding to multiple partners. We find that multi-specific binding is accommodated by at least two distinct patterns. In the simplest case, all partners share key interactions, and sequences optimized for binding to either single or multiple partners recover only a subset of native amino acid residues as optimal. More interestingly, for signaling interfaces functioning as network "hubs," we identify a different, "multi-faceted" mode, where each binding partner prefers its own subset of wild-type residues within the promiscuous binding site. Here, integration of preferences across all partners results in sequences much more "native-like" than seen in optimization for any single binding partner alone, suggesting these interfaces are substantially optimized for multi-specificity. The two strategies make distinct predictions for interface evolution and design. Shared interfaces may be better small molecule targets, whereas multi-faceted interactions may be more "designable" for altered specificity patterns. The computational methodology presented here is generalizable for examining how naturally occurring protein sequences have been selected to satisfy a variety of positive and negative constraints, as well as for rationally designing proteins to have desired patterns of altered specificity.

  18. Protein space: a natural method for realizing the nature of protein universe.

    Science.gov (United States)

    Yu, Chenglong; Deng, Mo; Cheng, Shiu-Yuen; Yau, Shek-Chung; He, Rong L; Yau, Stephen S-T

    2013-02-07

    Current methods cannot tell us what the nature of the protein universe is concretely. They are based on different models of amino acid substitution and multiple sequence alignment which is an NP-hard problem and requires manual intervention. Protein structural analysis also gives a direction for mapping the protein universe. Unfortunately, now only a minuscule fraction of proteins' 3-dimensional structures are known. Furthermore, the phylogenetic tree representations are not unique for any existing tree construction methods. Here we develop a novel method to realize the nature of protein universe. We show the protein universe can be realized as a protein space in 60-dimensional Euclidean space using a distance based on a normalized distribution of amino acids. Every protein is in one-to-one correspondence with a point in protein space, where proteins with similar properties stay close together. Thus the distance between two points in protein space represents the biological distance of the corresponding two proteins. We also propose a natural graphical representation for inferring phylogenies. The representation is natural and unique based on the biological distances of proteins in protein space. This will solve the fundamental question of how proteins are distributed in the protein universe. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Massively parallel de novo protein design for targeted therapeutics

    KAUST Repository

    Chevalier, Aaron; Silva, Daniel-Adriano; Rocklin, Gabriel J.; Hicks, Derrick R.; Vergara, Renan; Murapa, Patience; Bernard, Steffen M.; Zhang, Lu; Lam, Kwok-Ho; Yao, Guorui; Bahl, Christopher D.; Miyashita, Shin-Ichiro; Goreshnik, Inna; Fuller, James T.; Koday, Merika T.; Jenkins, Cody M.; Colvin, Tom; Carter, Lauren; Bohn, Alan; Bryan, Cassie M.; Ferná ndez-Velasco, D. Alejandro; Stewart, Lance; Dong, Min; Huang, Xuhui; Jin, Rongsheng; Wilson, Ian A.; Fuller, Deborah H.; Baker, David

    2017-01-01

    De novo protein design holds promise for creating small stable proteins with shapes customized to bind therapeutic targets. We describe a massively parallel approach for designing, manufacturing and screening mini-protein binders, integrating large-scale computational design, oligonucleotide synthesis, yeast display screening and next-generation sequencing. We designed and tested 22,660 mini-proteins of 37-43 residues that target influenza haemagglutinin and botulinum neurotoxin B, along with 6,286 control sequences to probe contributions to folding and binding, and identified 2,618 high-affinity binders. Comparison of the binding and non-binding design sets, which are two orders of magnitude larger than any previously investigated, enabled the evaluation and improvement of the computational model. Biophysical characterization of a subset of the binder designs showed that they are extremely stable and, unlike antibodies, do not lose activity after exposure to high temperatures. The designs elicit little or no immune response and provide potent prophylactic and therapeutic protection against influenza, even after extensive repeated dosing.

  20. Massively parallel de novo protein design for targeted therapeutics

    KAUST Repository

    Chevalier, Aaron

    2017-09-26

    De novo protein design holds promise for creating small stable proteins with shapes customized to bind therapeutic targets. We describe a massively parallel approach for designing, manufacturing and screening mini-protein binders, integrating large-scale computational design, oligonucleotide synthesis, yeast display screening and next-generation sequencing. We designed and tested 22,660 mini-proteins of 37-43 residues that target influenza haemagglutinin and botulinum neurotoxin B, along with 6,286 control sequences to probe contributions to folding and binding, and identified 2,618 high-affinity binders. Comparison of the binding and non-binding design sets, which are two orders of magnitude larger than any previously investigated, enabled the evaluation and improvement of the computational model. Biophysical characterization of a subset of the binder designs showed that they are extremely stable and, unlike antibodies, do not lose activity after exposure to high temperatures. The designs elicit little or no immune response and provide potent prophylactic and therapeutic protection against influenza, even after extensive repeated dosing.

  1. Massively parallel de novo protein design for targeted therapeutics

    Science.gov (United States)

    Chevalier, Aaron; Silva, Daniel-Adriano; Rocklin, Gabriel J.; Hicks, Derrick R.; Vergara, Renan; Murapa, Patience; Bernard, Steffen M.; Zhang, Lu; Lam, Kwok-Ho; Yao, Guorui; Bahl, Christopher D.; Miyashita, Shin-Ichiro; Goreshnik, Inna; Fuller, James T.; Koday, Merika T.; Jenkins, Cody M.; Colvin, Tom; Carter, Lauren; Bohn, Alan; Bryan, Cassie M.; Fernández-Velasco, D. Alejandro; Stewart, Lance; Dong, Min; Huang, Xuhui; Jin, Rongsheng; Wilson, Ian A.; Fuller, Deborah H.; Baker, David

    2018-01-01

    De novo protein design holds promise for creating small stable proteins with shapes customized to bind therapeutic targets. We describe a massively parallel approach for designing, manufacturing and screening mini-protein binders, integrating large-scale computational design, oligonucleotide synthesis, yeast display screening and next-generation sequencing. We designed and tested 22,660 mini-proteins of 37–43 residues that target influenza haemagglutinin and botulinum neurotoxin B, along with 6,286 control sequences to probe contributions to folding and binding, and identified 2,618 high-affinity binders. Comparison of the binding and non-binding design sets, which are two orders of magnitude larger than any previously investigated, enabled the evaluation and improvement of the computational model. Biophysical characterization of a subset of the binder designs showed that they are extremely stable and, unlike antibodies, do not lose activity after exposure to high temperatures. The designs elicit little or no immune response and provide potent prophylactic and therapeutic protection against influenza, even after extensive repeated dosing. PMID:28953867

  2. Financial methods for waterflooding injectate design

    Science.gov (United States)

    Heneman, Helmuth J.; Brady, Patrick V.

    2017-08-08

    A method of selecting an injectate for recovering liquid hydrocarbons from a reservoir includes designing a plurality of injectates, calculating a net present value of each injectate, and selecting a candidate injectate based on the net present value. For example, the candidate injectate may be selected to maximize the net present value of a waterflooding operation.

  3. Design Methods for Young Sustainable Architecture Practice

    NARCIS (Netherlands)

    Jauslin, D.; Drexler, H.; Curiel, F.

    2012-01-01

    This paper introduces landscape aesthetics as an innovative design method for sustainable architecture. It is based on the framework of a recent paper where the young and unfamous authors criticized three of the most prominent? architects today in regard to sustainable architecture and its

  4. Airfoils and method for designing airfoils

    DEFF Research Database (Denmark)

    2010-01-01

    The present invention relates to airfoils and design and design optimization of airfoils, in particular airfoils of rotor blades for wind turbines. One aspect of the invention relates to an airfoil with an external shape provided by an airfoil profile defined by a limited number of parameters......, such as a set of parameters. Another aspect of the invention relates to a method for designing an airfoil by means of an analytical airfoil profile, said method comprising the step of applying a conformal mapping to a near circle in a near circle plane, wherein the near circle is at least partly expressed...... by means of an analytical function, said conformal mapping transforming the near circle in the near circle plane to the airfoil profile in an airfoil plane. L...

  5. The research methods and model of protein turnover in animal

    International Nuclear Information System (INIS)

    Wu Xilin; Yang Feng

    2002-01-01

    The author discussed the concept and research methods of protein turnover in animal body. The existing problems and the research results of animal protein turnover in recent years were presented. Meanwhile, the measures to improve the models of animal protein turnover were analyzed

  6. New trends in reactor physics design methods

    International Nuclear Information System (INIS)

    Jagannathan, V.

    1993-01-01

    Reactor physics design methods are aimed at safe and efficient management of nuclear materials in a reactor core. The design methodologies require a high level of integration of different calculational modules of many a key areas like neutronics, thermal hydraulics, radiation transport etc in order to follow different 3-D phenomena under normal and transient operating conditions. The evolution of computer hardware technology is far more rapid than the software development and has rendered such integration a meaningful and realizable proposition. The aim of this paper is to assess the state of art of the physics design codes used in Indian thermal power reactor applications with respect to meeting the design, operational and safety requirements. (author). 50 refs

  7. Guaranteed Discrete Energy Optimization on Large Protein Design Problems.

    Science.gov (United States)

    Simoncini, David; Allouche, David; de Givry, Simon; Delmas, Céline; Barbe, Sophie; Schiex, Thomas

    2015-12-08

    In Computational Protein Design (CPD), assuming a rigid backbone and amino-acid rotamer library, the problem of finding a sequence with an optimal conformation is NP-hard. In this paper, using Dunbrack's rotamer library and Talaris2014 decomposable energy function, we use an exact deterministic method combining branch and bound, arc consistency, and tree-decomposition to provenly identify the global minimum energy sequence-conformation on full-redesign problems, defining search spaces of size up to 10(234). This is achieved on a single core of a standard computing server, requiring a maximum of 66GB RAM. A variant of the algorithm is able to exhaustively enumerate all sequence-conformations within an energy threshold of the optimum. These proven optimal solutions are then used to evaluate the frequencies and amplitudes, in energy and sequence, at which an existing CPD-dedicated simulated annealing implementation may miss the optimum on these full redesign problems. The probability of finding an optimum drops close to 0 very quickly. In the worst case, despite 1,000 repeats, the annealing algorithm remained more than 1 Rosetta unit away from the optimum, leading to design sequences that could differ from the optimal sequence by more than 30% of their amino acids.

  8. Participatory Design Methods for Collaboration and Communication

    Directory of Open Access Journals (Sweden)

    Tara Wood

    2017-01-01

    Full Text Available Website redesigns can be contentious and fraught in any type of organization, and libraries are no exception. Coming to consensus on priorities and design decisions is nearly impossible, as different groups compete to ensure their subject or specialty area is represented. To keep projects on track and on time, libraries may give a few staff members the authority to make all of the decisions, while keeping user research limited to a small number of usability tests. While these tactics are sometimes necessary, at best they can leave many feeling left out of the process, and at worst, can result in major oversights in the final design. Participatory design methods can bring users and stakeholders into the design process and ultimately lead to a better design and less friction in the project. The authors share their experience and lessons learned using participatory design techniques in a website redesign project at a large, multi-location academic library, and how these techniques facilitated communication, shaped design decisions, and kept a complex, difficult project on track.

  9. 3.6 simplified methods for design

    International Nuclear Information System (INIS)

    Nickell, R.E.; Yahr, G.T.

    1981-01-01

    Simplified design analysis methods for elevated temperature construction are classified and reviewed. Because the major impetus for developing elevated temperature design methodology during the past ten years has been the LMFBR program, considerable emphasis is placed upon results from this source. The operating characteristics of the LMFBR are such that cycles of severe transient thermal stresses can be interspersed with normal elevated temperature operational periods of significant duration, leading to a combination of plastic and creep deformation. The various simplified methods are organized into two general categories, depending upon whether it is the material, or constitutive, model that is reduced, or the geometric modeling that is simplified. Because the elastic representation of material behavior is so prevalent, an entire section is devoted to elastic analysis methods. Finally, the validation of the simplified procedures is discussed

  10. Bioactive L acidissima protein hydrolysates using Box-Behnken design.

    Science.gov (United States)

    Sonawane, Sachin K; Arya, Shalini S

    2017-07-01

    This study examines the extraction and hydrolysis of proteins using single factor and Box-Behnken Design (BBD). From single factor tests, optimised extraction parameters were 1% alkali concentration, 40 °C temperature, 60 min time, and 1:20 solid to alkali ratio. Under these conditions; 924.31 mg/g of total protein was obtained from Limonia acidissima (L acidissima). The maximum degree of hydrolysis was 39.82% at pH 2, enzyme to substrate ratio 2.5% (w/w), and hydrolysis time was 42.41 min using BBD design. L acidissima seed protein hydrolysate showed 32.94% DPPH and 88.18% of ABTS activity at concentration of 100 µg/ml and 1 mg/ml, respectively. Reducing power of 0.16 and metal chelating activity of 87.39% was obtained from 5 mg/ml protein hydrolysates. This implied that L acidissima seed protein hydrolysate could be utilised in protein rich product or as protein supplements.

  11. Cell-free system for synthesizing membrane proteins cell free method for synthesizing membrane proteins

    Science.gov (United States)

    Laible, Philip D; Hanson, Deborah K

    2013-06-04

    The invention provides an in vitro method for producing proteins, membrane proteins, membrane-associated proteins, and soluble proteins that interact with membrane-associated proteins for assembly into an oligomeric complex or that require association with a membrane for proper folding. The method comprises, supplying intracytoplasmic membranes from organisms; modifying protein composition of intracytoplasmic membranes from organism by modifying DNA to delete genes encoding functions of the organism not associated with the formation of the intracytoplasmic membranes; generating appropriate DNA or RNA templates that encode the target protein; and mixing the intracytoplasmic membranes with the template and a transcription/translation-competent cellular extract to cause simultaneous production of the membrane proteins and encapsulation of the membrane proteins within the intracytoplasmic membranes.

  12. Developments of an Interactive Sail Design Method

    OpenAIRE

    S. M. Malpede; M. Vezza

    2000-01-01

    This paper presents a new tool for performing the integrated design and analysis of a sail. The features of the system are the geometrical definition of a sail shape, using the Bezier surface method, the creation of a finite element model for the non-linear structural analysis and a fluid-dynamic model for the aerodynamic analysis. The system has been developed using MATLAB(r). Recent sail design efforts have been focused on solving the aeroelastic behavior of the sail. The pressure dis...

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

    Science.gov (United States)

    Gauthier, Marc A; Klok, Harm-Anton

    2008-06-21

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

  14. Sampling and energy evaluation challenges in ligand binding protein design.

    Science.gov (United States)

    Dou, Jiayi; Doyle, Lindsey; Jr Greisen, Per; Schena, Alberto; Park, Hahnbeom; Johnsson, Kai; Stoddard, Barry L; Baker, David

    2017-12-01

    The steroid hormone 17α-hydroxylprogesterone (17-OHP) is a biomarker for congenital adrenal hyperplasia and hence there is considerable interest in development of sensors for this compound. We used computational protein design to generate protein models with binding sites for 17-OHP containing an extended, nonpolar, shape-complementary binding pocket for the four-ring core of the compound, and hydrogen bonding residues at the base of the pocket to interact with carbonyl and hydroxyl groups at the more polar end of the ligand. Eight of 16 designed proteins experimentally tested bind 17-OHP with micromolar affinity. A co-crystal structure of one of the designs revealed that 17-OHP is rotated 180° around a pseudo-two-fold axis in the compound and displays multiple binding modes within the pocket, while still interacting with all of the designed residues in the engineered site. Subsequent rounds of mutagenesis and binding selection improved the ligand affinity to nanomolar range, while appearing to constrain the ligand to a single bound conformation that maintains the same "flipped" orientation relative to the original design. We trace the discrepancy in the design calculations to two sources: first, a failure to model subtle backbone changes which alter the distribution of sidechain rotameric states and second, an underestimation of the energetic cost of desolvating the carbonyl and hydroxyl groups of the ligand. The difference between design model and crystal structure thus arises from both sampling limitations and energy function inaccuracies that are exacerbated by the near two-fold symmetry of the molecule. © 2017 The Authors Protein Science published by Wiley Periodicals, Inc. on behalf of The Protein Society.

  15. Automated design evolution of stereochemically randomized protein foldamers

    Science.gov (United States)

    Ranbhor, Ranjit; Kumar, Anil; Patel, Kirti; Ramakrishnan, Vibin; Durani, Susheel

    2018-05-01

    Diversification of chain stereochemistry opens up the possibilities of an ‘in principle’ increase in the design space of proteins. This huge increase in the sequence and consequent structural variation is aimed at the generation of smart materials. To diversify protein structure stereochemically, we introduced L- and D-α-amino acids as the design alphabet. With a sequence design algorithm, we explored the usage of specific variables such as chirality and the sequence of this alphabet in independent steps. With molecular dynamics, we folded stereochemically diverse homopolypeptides and evaluated their ‘fitness’ for possible design as protein-like foldamers. We propose a fitness function to prune the most optimal fold among 1000 structures simulated with an automated repetitive simulated annealing molecular dynamics (AR-SAMD) approach. The highly scored poly-leucine fold with sequence lengths of 24 and 30 amino acids were later sequence-optimized using a Dead End Elimination cum Monte Carlo based optimization tool. This paper demonstrates a novel approach for the de novo design of protein-like foldamers.

  16. Can understanding the packing of side chains improve the design of protein-protein interactions?

    Science.gov (United States)

    Zhou, Alice; O'Hern, Corey; Regan, Lynne

    2011-03-01

    With the long-term goal to improve the design of protein-protein interactions, we have begun extensive computational studies to understand how side-chains of key residues of binding partners geometrically fit together at protein-peptide interfaces, e.g. the tetratrico-peptide repeat protein and its cognate peptide). We describe simple atomic-scale models of hydrophobic dipeptides, which include hard-core repulsion, bond length and angle constraints, and Van der Waals attraction. By completely enumerating all minimal energy structures in these systems, we are able to reproduce important features of the probability distributions of side chain dihedral angles of hydrophic residues in the protein data bank. These results are the crucial first step in developing computational models that can predict the side chain conformations of residues at protein-peptide interfaces. CSO acknowledges support from NSF grant no. CMMT-1006527.

  17. Design method for fluid viscous dampers

    Energy Technology Data Exchange (ETDEWEB)

    Jia, Jiuhong; Hua, Hongxing [Shanghai Jiaotong University, State Key Laboratory of Mechanical System and Vibration, Shanghai (China); Du, Jianye; Wang, Yu [Naval Arming Academy, Institute of Naval Vessels, Beijing (China)

    2008-09-15

    A basic design method of doubly acting fluid viscous dampers with double guide bars is presented. The flow of the viscoelastic fluid between two parallel plates, one of which is started suddenly and the other of which is still, is analyzed. According to this solution, the velocity and the shear stress of the fluid at the fringe of the piston are solved approximately. A mathematical model of viscous dampers is derived, and the shock test is carried out. From experimental results, the parameters of the mathematical model are determined. Consequently, a semi-empirical design equation is obtained. Applying this equation to a certain practical damper, the damping material is chosen and the physical dimensions of the damper are determined. Shock tests using this damper are performed. Theoretical results are in good agreement with experimental results, which validates the reliability of the calculated physical dimensions of the specimen damper and the validity of the basic design equation. (orig.)

  18. An efficient method for sampling the essential subspace of proteins

    NARCIS (Netherlands)

    Amadei, A; Linssen, A.B M; de Groot, B.L.; van Aalten, D.M.F.; Berendsen, H.J.C.

    A method is presented for a more efficient sampling of the configurational space of proteins as compared to conventional sampling techniques such as molecular dynamics. The method is based on the large conformational changes in proteins revealed by the ''essential dynamics'' analysis. A form of

  19. Advance of core design method for ATR

    International Nuclear Information System (INIS)

    Maeda, Seiichirou; Ihara, Toshiteru; Iijima, Takashi; Seino, Hideaki; Kobayashi, Tetsurou; Takeuchi, Michio; Sugawara, Satoru; Matsumoto, Mitsuo.

    1995-01-01

    Core characteristics of ATR demonstration plant has been revised such as increasing the fuel burnup and the channel power, which is achieved by changing the number of fuel rod per fuel assembly from 28 to 36. The research and development concerning the core design method for ATR have been continued. The calculational errors of core analysis code have been evaluated using the operational data of FUGEN and the full scale simulated test results in DCA (Deuterium Critical Assembly) and HTL (Heat Transfer Loop) at O-arai engineering center. It is confirmed that the calculational error of power distribution is smaller than the design value of ATR demonstration plant. Critical heat flux correlation curve for 36 fuel rod cluster has been developed and the probability evaluation method based on its curve, which is more rational to evaluate the fuel dryout, has been adopted. (author)

  20. An Empirical Method for Particle Damping Design

    Directory of Open Access Journals (Sweden)

    Zhi Wei Xu

    2004-01-01

    Full Text Available Particle damping is an effective vibration suppression method. The purpose of this paper is to develop an empirical method for particle damping design based on extensive experiments on three structural objects – steel beam, bond arm and bond head stand. The relationships among several key parameters of structure/particles are obtained. Then the procedures with the use of particle damping are proposed to provide guidelines for practical applications. It is believed that the results presented in this paper would be helpful to effectively implement the particle damping for various structural systems for the purpose of vibration suppression.

  1. Engineering design of systems models and methods

    CERN Document Server

    Buede, Dennis M

    2009-01-01

    The ideal introduction to the engineering design of systems-now in a new edition. The Engineering Design of Systems, Second Edition compiles a wealth of information from diverse sources to provide a unique, one-stop reference to current methods for systems engineering. It takes a model-based approach to key systems engineering design activities and introduces methods and models used in the real world. Features new to this edition include: * The addition of Systems Modeling Language (SysML) to several of the chapters, as well as the introduction of new terminology * Additional material on partitioning functions and components * More descriptive material on usage scenarios based on literature from use case development * Updated homework assignments * The software product CORE (from Vitech Corporation) is used to generate the traditional SE figures and the software product MagicDraw UML with SysML plugins (from No Magic, Inc.) is used for the SysML figures This book is designed to be an introductory reference ...

  2. Design Methods for Young Sustainable Architecture Practice

    OpenAIRE

    Jauslin, D.; Drexler, H.; Curiel, F.

    2012-01-01

    This paper introduces landscape aesthetics as an innovative design method for sustainable architecture. It is based on the framework of a recent paper where the young and unfamous authors criticized three of the most prominent? architects today in regard to sustainable architecture and its aesthetics. Leading architects expressed their skepticism as to whether there is such a thing as aesthetics in sustainable architecture, or for that matter, if architecture can indeed be sustainable at all....

  3. A method for investigating protein-protein interactions related to Salmonella typhimurium pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Chowdhury, Saiful M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Shi, Liang [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Yoon, Hyunjin [Dartmouth College, Hanover, NH (United States); Ansong, Charles [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Rommereim, Leah M. [Dartmouth College, Hanover, NH (United States); Norbeck, Angela D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Auberry, Kenneth J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Moore, R. J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Adkins, Joshua N. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Heffron, Fred [Oregon Health and Science Univ., Portland, OR (United States); Smith, Richard D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2009-02-10

    We successfully modified an existing method to investigate protein-protein interactions in the pathogenic bacterium Salmonella typhimurium (STM). This method includes i) addition of a histidine-biotin-histidine tag to the bait proteins via recombinant DNA techniques; ii) in vivo cross-linking with formaldehyde; iii) tandem affinity purification of bait proteins under fully denaturing conditions; and iv) identification of the proteins cross-linked to the bait proteins by liquid-chromatography in conjunction with tandem mass-spectrometry. In vivo cross-linking stabilized protein interactions permitted the subsequent two-step purification step conducted under denaturing conditions. The two-step purification greatly reduced nonspecific binding of non-cross-linked proteins to bait proteins. Two different negative controls were employed to reduce false-positive identification. In an initial demonstration of this approach, we tagged three selected STM proteins- HimD, PduB and PhoP- with known binding partners that ranged from stable (e.g., HimD) to transient (i.e., PhoP). Distinct sets of interacting proteins were identified with each bait protein, including the known binding partners such as HimA for HimD, as well as anticipated and unexpected binding partners. Our results suggest that novel protein-protein interactions may be critical to pathogenesis by Salmonella typhimurium. .

  4. Protein design on computers. Five new proteins: Shpilka, Grendel, Fingerclasp, Leather, and Aida.

    Science.gov (United States)

    Sander, C; Vriend, G; Bazan, F; Horovitz, A; Nakamura, H; Ribas, L; Finkelstein, A V; Lockhart, A; Merkl, R; Perry, L J

    1992-02-01

    What is the current state of the art in protein design? This question was approached in a recent two-week protein design workshop sponsored by EMBO and held at the EMBL in Heidelberg. The goals were to test available design tools and to explore new design strategies. Five novel proteins were designed: Shpilka, a sandwich of two four-stranded beta-sheets, a scaffold on which to explore variations in loop topology; Grendel, a four-helical membrane anchor, ready for fusion to water-soluble functional domains; Finger-clasp, a dimer of interdigitating beta-beta-alpha units, the simplest variant of the "handshake" structural class; Aida, an antibody binding surface intended to be specific for flavodoxin; Leather--a minimal NAD binding domain, extracted from a larger protein. Each design is available as a set of three-dimensional coordinates, the corresponding amino acid sequence and a set of analytical results. The designs are placed in the public domain for scrutiny, improvement, and possible experimental verification.

  5. A brief review of other notable protein blotting methods.

    Science.gov (United States)

    Kurien, Biji T; Scofield, R Hal

    2009-01-01

    A plethora of methods have been used for transferring proteins from the gel to the membrane. These include centrifuge blotting, electroblotting of proteins to Teflon tape and membranes for N- and C-terminal sequence analysis, multiple tissue blotting, a two-step transfer of low and high molecular weight proteins, blotting of Coomassie Brilliant Blue (CBB)-stained proteins from polyacrylamide gels to transparencies, acid electroblotting onto activated glass, membrane-array method for the detection of human intestinal bacteria in fecal samples, protein microarray using a new black cellulose nitrate support, electrotransfer using square wave alternating voltage for enhanced protein recovery, polyethylene glycol-mediated significant enhancement of the immunoblotting transfer, parallel protein chemical processing before and during western blot and the molecular scanner concept, electronic western blot of matrix-assisted laser desorption/ionization (MALDI) mass spectrometry-identified polypeptides from parallel processed gel-separated proteins, semidry electroblotting of peptides and proteins from acid-urea polyacrylamide gels, transfer of silver-stained proteins from polyacrylamide gels to polyvinylidene difluoride (PVDF) membranes, and the display of K(+) channel proteins on a solid nitrocellulose support for assaying toxin binding. The quantification of proteins bound to PVDF membranes by elution of CBB, clarification of immunoblots on PVDF for transmission densitometry, gold coating of nonconductive membranes before MALDI tandem mass spectrometric analysis to prevent charging effect for analysis of peptides from PVDF membranes, and a simple method for coating native polysaccharides onto nitrocellulose are some of the methods involving either the manipulation of membranes with transferred proteins or just a passive transfer of antigens to membranes. All these methods are briefly reviewed in this chapter.

  6. Evolutionary optimization methods for accelerator design

    Science.gov (United States)

    Poklonskiy, Alexey A.

    Many problems from the fields of accelerator physics and beam theory can be formulated as optimization problems and, as such, solved using optimization methods. Despite growing efficiency of the optimization methods, the adoption of modern optimization techniques in these fields is rather limited. Evolutionary Algorithms (EAs) form a relatively new and actively developed optimization methods family. They possess many attractive features such as: ease of the implementation, modest requirements on the objective function, a good tolerance to noise, robustness, and the ability to perform a global search efficiently. In this work we study the application of EAs to problems from accelerator physics and beam theory. We review the most commonly used methods of unconstrained optimization and describe the GATool, evolutionary algorithm and the software package, used in this work, in detail. Then we use a set of test problems to assess its performance in terms of computational resources, quality of the obtained result, and the tradeoff between them. We justify the choice of GATool as a heuristic method to generate cutoff values for the COSY-GO rigorous global optimization package for the COSY Infinity scientific computing package. We design the model of their mutual interaction and demonstrate that the quality of the result obtained by GATool increases as the information about the search domain is refined, which supports the usefulness of this model. We Giscuss GATool's performance on the problems suffering from static and dynamic noise and study useful strategies of GATool parameter tuning for these and other difficult problems. We review the challenges of constrained optimization with EAs and methods commonly used to overcome them. We describe REPA, a new constrained optimization method based on repairing, in exquisite detail, including the properties of its two repairing techniques: REFIND and REPROPT. We assess REPROPT's performance on the standard constrained

  7. Advances on geometric flux optical design method

    Science.gov (United States)

    García-Botella, Ángel; Fernández-Balbuena, Antonio Álvarez; Vázquez, Daniel

    2017-09-01

    Nonimaging optics is focused on the study of methods to design concentrators or illuminators systems. It can be included in the area of photometry and radiometry and it is governed by the laws of geometrical optics. The field vector method, which starts with the definition of the irradiance vector E, is one of the techniques used in nonimaging optics. Called "Geometrical flux vector" it has provide ideal designs. The main property of this model is, its ability to estimate how radiant energy is transferred by the optical system, from the concepts of field line, flux tube and pseudopotential surface, overcoming traditional raytrace methods. Nevertheless this model has been developed only at an academic level, where characteristic optical parameters are ideal not real and the studied geometries are simple. The main objective of the present paper is the application of the vector field method to the analysis and design of real concentration and illumination systems. We propose the development of a calculation tool for optical simulations by vector field, using algorithms based on Fermat`s principle, as an alternative to traditional tools for optical simulations by raytrace, based on reflection and refraction law. This new tool provides, first, traditional simulations results: efficiency, illuminance/irradiance calculations, angular distribution of light- with lower computation time, photometrical information needs about a few tens of field lines, in comparison with million rays needed nowadays. On the other hand the tool will provides new information as vector field maps produced by the system, composed by field lines and quasipotential surfaces. We show our first results with the vector field simulation tool.

  8. Protein design in systems metabolic engineering for industrial strain development.

    Science.gov (United States)

    Chen, Zhen; Zeng, An-Ping

    2013-05-01

    Accelerating the process of industrial bacterial host strain development, aimed at increasing productivity, generating new bio-products or utilizing alternative feedstocks, requires the integration of complementary approaches to manipulate cellular metabolism and regulatory networks. Systems metabolic engineering extends the concept of classical metabolic engineering to the systems level by incorporating the techniques used in systems biology and synthetic biology, and offers a framework for the development of the next generation of industrial strains. As one of the most useful tools of systems metabolic engineering, protein design allows us to design and optimize cellular metabolism at a molecular level. Here, we review the current strategies of protein design for engineering cellular synthetic pathways, metabolic control systems and signaling pathways, and highlight the challenges of this subfield within the context of systems metabolic engineering. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Other notable protein blotting methods: a brief review.

    Science.gov (United States)

    Kurien, Biji T; Scofield, R Hal

    2015-01-01

    Proteins have been transferred from the gel to the membrane by a variety of methods. These include vacuum blotting, centrifuge blotting, electroblotting of proteins to Teflon tape and membranes for N- and C-terminal sequence analysis, multiple tissue blotting, a two-step transfer of low- and high-molecular-weight proteins, acid electroblotting onto activated glass, membrane-array method for the detection of human intestinal bacteria in fecal samples, protein microarray using a new black cellulose nitrate support, electrotransfer using square wave alternating voltage for enhanced protein recovery, polyethylene glycol-mediated significant enhancement of the immunoblotting transfer, parallel protein chemical processing before and during western blot and the molecular scanner concept, electronic western blot of matrix-assisted laser desorption/ionization mass spectrometric-identified polypeptides from parallel processed gel-separated proteins, semidry electroblotting of peptides and proteins from acid-urea polyacrylamide gels, transfer of silver-stained proteins from polyacrylamide gels to polyvinylidene difluoride (PVDF) membranes, and the display of K(+) channel proteins on a solid nitrocellulose support for assaying toxin binding. The quantification of proteins bound to PVDF membranes by elution of CBB, clarification of immunoblots on PVDF for transmission densitometry, gold coating of nonconductive membranes before matrix-assisted laser desorption/ionization tandem mass spectrometric analysis to prevent charging effect for analysis of peptides from PVDF membranes, and a simple method for coating native polysaccharides onto nitrocellulose are some of the methods involving either the manipulation of membranes with transferred proteins or just a passive transfer of antigens to membranes. All these methods are briefly reviewed in this chapter.

  10. Protein array staining methods for undefined protein content, manufacturing quality control, and performance validation.

    Science.gov (United States)

    Schabacker, Daniel S; Stefanovska, Ivana; Gavin, Igor; Pedrak, Casandra; Chandler, Darrell P

    2006-12-01

    Methods to assess the quality and performance of protein microarrays fabricated from undefined protein content are required to elucidate slide-to-slide variability and interpolate resulting signal intensity values after an interaction assay. We therefore developed several simple total- and posttranslational modification-specific, on-chip staining methods to quantitatively assess the quality of gel element protein arrays manufactured with whole-cell lysate in vitro protein fractions derived from two-dimensional liquid-phase fractionation (PF2D) technology. A linear dynamic range of at least 3 logs was observed for protein stains and immobilized protein content, with a lower limit of detection at 8 pg of protein per gel element with Deep Purple protein stain and a field-portable microarray imager. Data demonstrate the successful isolation, separation, transfer, and immobilization of putative transmembrane proteins from Yersinia pestis KIM D27 with the combined PF2D and gel element array method. Internal bovine serum albumin standard curves provided a method to assess on-chip PF2D transfer and quantify total protein immobilized per gel element. The basic PF2D array fabrication and quality assurance/quality control methods described here therefore provide a standard operating procedure and basis for developing whole-proteome arrays for interrogating host-pathogen interactions, independent of sequenced genomes, affinity tags, or a priori knowledge of target cell composition.

  11. New design methods for computer aided architecturald design methodology teaching

    NARCIS (Netherlands)

    Achten, H.H.

    2003-01-01

    Architects and architectural students are exploring new ways of design using Computer Aided Architectural Design software. This exploration is seldom backed up from a design methodological viewpoint. In this paper, a design methodological framework for reflection on innovate design processes by

  12. Combining Rosetta with molecular dynamics (MD): A benchmark of the MD-based ensemble protein design.

    Science.gov (United States)

    Ludwiczak, Jan; Jarmula, Adam; Dunin-Horkawicz, Stanislaw

    2018-07-01

    Computational protein design is a set of procedures for computing amino acid sequences that will fold into a specified structure. Rosetta Design, a commonly used software for protein design, allows for the effective identification of sequences compatible with a given backbone structure, while molecular dynamics (MD) simulations can thoroughly sample near-native conformations. We benchmarked a procedure in which Rosetta design is started on MD-derived structural ensembles and showed that such a combined approach generates 20-30% more diverse sequences than currently available methods with only a slight increase in computation time. Importantly, the increase in diversity is achieved without a loss in the quality of the designed sequences assessed by their resemblance to natural sequences. We demonstrate that the MD-based procedure is also applicable to de novo design tasks started from backbone structures without any sequence information. In addition, we implemented a protocol that can be used to assess the stability of designed models and to select the best candidates for experimental validation. In sum our results demonstrate that the MD ensemble-based flexible backbone design can be a viable method for protein design, especially for tasks that require a large pool of diverse sequences. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. HomPPI: a class of sequence homology based protein-protein interface prediction methods

    Directory of Open Access Journals (Sweden)

    Dobbs Drena

    2011-06-01

    Full Text Available Abstract Background Although homology-based methods are among the most widely used methods for predicting the structure and function of proteins, the question as to whether interface sequence conservation can be effectively exploited in predicting protein-protein interfaces has been a subject of debate. Results We studied more than 300,000 pair-wise alignments of protein sequences from structurally characterized protein complexes, including both obligate and transient complexes. We identified sequence similarity criteria required for accurate homology-based inference of interface residues in a query protein sequence. Based on these analyses, we developed HomPPI, a class of sequence homology-based methods for predicting protein-protein interface residues. We present two variants of HomPPI: (i NPS-HomPPI (Non partner-specific HomPPI, which can be used to predict interface residues of a query protein in the absence of knowledge of the interaction partner; and (ii PS-HomPPI (Partner-specific HomPPI, which can be used to predict the interface residues of a query protein with a specific target protein. Our experiments on a benchmark dataset of obligate homodimeric complexes show that NPS-HomPPI can reliably predict protein-protein interface residues in a given protein, with an average correlation coefficient (CC of 0.76, sensitivity of 0.83, and specificity of 0.78, when sequence homologs of the query protein can be reliably identified. NPS-HomPPI also reliably predicts the interface residues of intrinsically disordered proteins. Our experiments suggest that NPS-HomPPI is competitive with several state-of-the-art interface prediction servers including those that exploit the structure of the query proteins. The partner-specific classifier, PS-HomPPI can, on a large dataset of transient complexes, predict the interface residues of a query protein with a specific target, with a CC of 0.65, sensitivity of 0.69, and specificity of 0.70, when homologs of

  14. Elfin: An algorithm for the computational design of custom three-dimensional structures from modular repeat protein building blocks.

    Science.gov (United States)

    Yeh, Chun-Ting; Brunette, T J; Baker, David; McIntosh-Smith, Simon; Parmeggiani, Fabio

    2018-02-01

    Computational protein design methods have enabled the design of novel protein structures, but they are often still limited to small proteins and symmetric systems. To expand the size of designable proteins while controlling the overall structure, we developed Elfin, a genetic algorithm for the design of novel proteins with custom shapes using structural building blocks derived from experimentally verified repeat proteins. By combining building blocks with compatible interfaces, it is possible to rapidly build non-symmetric large structures (>1000 amino acids) that match three-dimensional geometric descriptions provided by the user. A run time of about 20min on a laptop computer for a 3000 amino acid structure makes Elfin accessible to users with limited computational resources. Protein structures with controlled geometry will allow the systematic study of the effect of spatial arrangement of enzymes and signaling molecules, and provide new scaffolds for functional nanomaterials. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. DESIGN OPTIMIZATION METHOD USED IN MECHANICAL ENGINEERING

    Directory of Open Access Journals (Sweden)

    SCURTU Iacob Liviu

    2016-11-01

    Full Text Available This paper presents an optimization study in mechanical engineering. First part of the research describe the structural optimization method used, followed by the presentation of several optimization studies conducted in recent years. The second part of the paper presents the CAD modelling of an agricultural plough component. The beam of the plough is analysed using finite element method. The plough component is meshed in solid elements, and the load case which mimics the working conditions of agricultural equipment of this are created. The model is prepared to find the optimal structural design, after the FEA study of the model is done. The mass reduction of part is the criterion applied for this optimization study. The end of this research presents the final results and the model optimized shape.

  16. [Detection of protein-protein interactions by FRET and BRET methods].

    Science.gov (United States)

    Matoulková, E; Vojtěšek, B

    2014-01-01

    Nowadays, in vivo protein-protein interaction studies have become preferable detecting meth-ods that enable to show or specify (already known) protein interactions and discover their inhibitors. They also facilitate detection of protein conformational changes and discovery or specification of signaling pathways in living cells. One group of in vivo methods enabling these findings is based on fluorescent resonance energy transfer (FRET) and its bio-luminescent modification (BRET). They are based on visualization of protein-protein interactions via light or enzymatic excitation of fluorescent or bio-luminescent proteins. These methods allow not only protein localization within the cell or its organelles (or small animals) but they also allow us to quantify fluorescent signals and to discover weak or strong interaction partners. In this review, we explain the principles of FRET and BRET, their applications in the characterization of protein-protein interactions and we describe several findings using these two methods that clarify molecular and cellular mechanisms and signals related to cancer biology.

  17. A new essential protein discovery method based on the integration of protein-protein interaction and gene expression data

    Directory of Open Access Journals (Sweden)

    Li Min

    2012-03-01

    Full Text Available Abstract Background Identification of essential proteins is always a challenging task since it requires experimental approaches that are time-consuming and laborious. With the advances in high throughput technologies, a large number of protein-protein interactions are available, which have produced unprecedented opportunities for detecting proteins' essentialities from the network level. There have been a series of computational approaches proposed for predicting essential proteins based on network topologies. However, the network topology-based centrality measures are very sensitive to the robustness of network. Therefore, a new robust essential protein discovery method would be of great value. Results In this paper, we propose a new centrality measure, named PeC, based on the integration of protein-protein interaction and gene expression data. The performance of PeC is validated based on the protein-protein interaction network of Saccharomyces cerevisiae. The experimental results show that the predicted precision of PeC clearly exceeds that of the other fifteen previously proposed centrality measures: Degree Centrality (DC, Betweenness Centrality (BC, Closeness Centrality (CC, Subgraph Centrality (SC, Eigenvector Centrality (EC, Information Centrality (IC, Bottle Neck (BN, Density of Maximum Neighborhood Component (DMNC, Local Average Connectivity-based method (LAC, Sum of ECC (SoECC, Range-Limited Centrality (RL, L-index (LI, Leader Rank (LR, Normalized α-Centrality (NC, and Moduland-Centrality (MC. Especially, the improvement of PeC over the classic centrality measures (BC, CC, SC, EC, and BN is more than 50% when predicting no more than 500 proteins. Conclusions We demonstrate that the integration of protein-protein interaction network and gene expression data can help improve the precision of predicting essential proteins. The new centrality measure, PeC, is an effective essential protein discovery method.

  18. Design, synthesis, and evaluation of an alpha-helix mimetic library targeting protein-protein interactions.

    Science.gov (United States)

    Shaginian, Alex; Whitby, Landon R; Hong, Sukwon; Hwang, Inkyu; Farooqi, Bilal; Searcey, Mark; Chen, Jiandong; Vogt, Peter K; Boger, Dale L

    2009-04-22

    The design and solution-phase synthesis of an alpha-helix mimetic library as an integral component of a small-molecule library targeting protein-protein interactions are described. The iterative design, synthesis, and evaluation of the candidate alpha-helix mimetic was initiated from a precedented triaryl template and refined by screening the designs for inhibition of MDM2/p53 binding. Upon identifying a chemically and biologically satisfactory design and consistent with the screening capabilities of academic collaborators, the corresponding complete library was assembled as 400 mixtures of 20 compounds (20 x 20 x 20-mix), where the added subunits are designed to mimic all possible permutations of the naturally occurring i, i + 4, i + 7 amino acid side chains of an alpha-helix. The library (8000 compounds) was prepared using a solution-phase synthetic protocol enlisting acid/base liquid-liquid extractions for purification on a scale that insures its long-term availability for screening campaigns. Screening of the library for inhibition of MDM2/p53 binding not only identified the lead alpha-helix mimetic upon which the library was based, but also suggests that a digestion of the initial screening results that accompany the use of such a comprehensive library can provide insights into the nature of the interaction (e.g., an alpha-helix mediated protein-protein interaction) and define the key residues and their characteristics responsible for recognition.

  19. Developments of an Interactive Sail Design Method

    Directory of Open Access Journals (Sweden)

    S. M. Malpede

    2000-01-01

    Full Text Available This paper presents a new tool for performing the integrated design and analysis of a sail. The features of the system are the geometrical definition of a sail shape, using the Bezier surface method, the creation of a finite element model for the non-linear structural analysis and a fluid-dynamic model for the aerodynamic analysis. The system has been developed using MATLAB(r. Recent sail design efforts have been focused on solving the aeroelastic behavior of the sail. The pressure distribution on a sail changes continuously, by virtue of cloth stretch and flexing. The sail shape determines the pressure distribution and, at the same time, the pressure distribution on the sail stretches and flexes the sail material determining its shape. This characteristic non-linear behavior requires iterative solution strategies to obtain the equilibrium configuration and evaluate the forces involved. The aeroelastic problem is tackled by combining structural with aerodynamic analysis. Firstly, pressure loads for a known sail-shape are computed (aerodynamic analysis. Secondly, the sail-shape is analyzed for the obtained external loads (structural analysis. The final solution is obtained by using an iterative analysis process, which involves both aerodynamic and the structural analysis. When the solution converges, it is possible to make design modifications.

  20. Improved means and methods for expressing recombinant proteins

    NARCIS (Netherlands)

    Poolman, Berend; Martinez Linares, Daniel; Gul, Nadia

    2014-01-01

    The invention relates to the field of genetic engineering and the production of recombinant proteins in microbial host cells. Provided is a method for enhanced expression of a recombinant protein of interest in a microbial host cell, comprising providing a microbial host cell wherein the function of

  1. Comparison of three methods for determination of protein ...

    African Journals Online (AJOL)

    However, a six fold greater amount of protein was obtained when FastPrep was applied to lyse LAB cells. Our results also indicate that, this fast and easy extraction method allows more spot-abundant polyacrylamide gels. More clear and consistent strips were detected by SDS-PAGE when proteins were extracted by ...

  2. Comparison of protein extraction methods suitable for proteomics ...

    African Journals Online (AJOL)

    An efficient protein extraction method is a prerequisite for successful implementation of proteomics. In this study, seedling roots of Jerusalem artichoke were treated with the concentration of 250 mM NaCl for 36 h. Subsequently, six different protocols of protein extraction were applied to seedling roots of Jerusalem artichoke ...

  3. Chemical Methods for Peptide and Protein Production

    Directory of Open Access Journals (Sweden)

    Istvan Toth

    2013-04-01

    Full Text Available Since the invention of solid phase synthetic methods by Merrifield in 1963, the number of research groups focusing on peptide synthesis has grown exponentially. However, the original step-by-step synthesis had limitations: the purity of the final product decreased with the number of coupling steps. After the development of Boc and Fmoc protecting groups, novel amino acid protecting groups and new techniques were introduced to provide high quality and quantity peptide products. Fragment condensation was a popular method for peptide production in the 1980s, but unfortunately the rate of racemization and reaction difficulties proved less than ideal. Kent and co-workers revolutionized peptide coupling by introducing the chemoselective reaction of unprotected peptides, called native chemical ligation. Subsequently, research has focused on the development of novel ligating techniques including the famous click reaction, ligation of peptide hydrazides, and the recently reported a-ketoacid-hydroxylamine ligations with 5-oxaproline. Several companies have been formed all over the world to prepare high quality Good Manufacturing Practice peptide products on a multi-kilogram scale. This review describes the advances in peptide chemistry including the variety of synthetic peptide methods currently available and the broad application of peptides in medicinal chemistry.

  4. Chemical methods for peptide and protein production.

    Science.gov (United States)

    Chandrudu, Saranya; Simerska, Pavla; Toth, Istvan

    2013-04-12

    Since the invention of solid phase synthetic methods by Merrifield in 1963, the number of research groups focusing on peptide synthesis has grown exponentially. However, the original step-by-step synthesis had limitations: the purity of the final product decreased with the number of coupling steps. After the development of Boc and Fmoc protecting groups, novel amino acid protecting groups and new techniques were introduced to provide high quality and quantity peptide products. Fragment condensation was a popular method for peptide production in the 1980s, but unfortunately the rate of racemization and reaction difficulties proved less than ideal. Kent and co-workers revolutionized peptide coupling by introducing the chemoselective reaction of unprotected peptides, called native chemical ligation. Subsequently, research has focused on the development of novel ligating techniques including the famous click reaction, ligation of peptide hydrazides, and the recently reported α-ketoacid-hydroxylamine ligations with 5-oxaproline. Several companies have been formed all over the world to prepare high quality Good Manufacturing Practice peptide products on a multi-kilogram scale. This review describes the advances in peptide chemistry including the variety of synthetic peptide methods currently available and the broad application of peptides in medicinal chemistry.

  5. Prediction of allosteric sites on protein surfaces with an elastic-network-model-based thermodynamic method.

    Science.gov (United States)

    Su, Ji Guo; Qi, Li Sheng; Li, Chun Hua; Zhu, Yan Ying; Du, Hui Jing; Hou, Yan Xue; Hao, Rui; Wang, Ji Hua

    2014-08-01

    Allostery is a rapid and efficient way in many biological processes to regulate protein functions, where binding of an effector at the allosteric site alters the activity and function at a distant active site. Allosteric regulation of protein biological functions provides a promising strategy for novel drug design. However, how to effectively identify the allosteric sites remains one of the major challenges for allosteric drug design. In the present work, a thermodynamic method based on the elastic network model was proposed to predict the allosteric sites on the protein surface. In our method, the thermodynamic coupling between the allosteric and active sites was considered, and then the allosteric sites were identified as those where the binding of an effector molecule induces a large change in the binding free energy of the protein with its ligand. Using the proposed method, two proteins, i.e., the 70 kD heat shock protein (Hsp70) and GluA2 alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor, were studied and the allosteric sites on the protein surface were successfully identified. The predicted results are consistent with the available experimental data, which indicates that our method is a simple yet effective approach for the identification of allosteric sites on proteins.

  6. Computational enzyme design: transitioning from catalytic proteins to enzymes.

    Science.gov (United States)

    Mak, Wai Shun; Siegel, Justin B

    2014-08-01

    The widespread interest in enzymes stem from their ability to catalyze chemical reactions under mild and ecologically friendly conditions with unparalleled catalytic proficiencies. While thousands of naturally occurring enzymes have been identified and characterized, there are still numerous important applications for which there are no biological catalysts capable of performing the desired chemical transformation. In order to engineer enzymes for which there is no natural starting point, efforts using a combination of quantum chemistry and force-field based protein molecular modeling have led to the design of novel proteins capable of catalyzing chemical reactions not catalyzed by naturally occurring enzymes. Here we discuss the current status and potential avenues to pursue as the field of computational enzyme design moves forward. Published by Elsevier Ltd.

  7. Chemical Methods to Knock Down the Amyloid Proteins

    Directory of Open Access Journals (Sweden)

    Na Gao

    2017-06-01

    Full Text Available Amyloid proteins are closely related with amyloid diseases and do tremendous harm to human health. However, there is still a lack of effective strategies to treat these amyloid diseases, so it is important to develop novel methods. Accelerating the clearance of amyloid proteins is a favorable method for amyloid disease treatment. Recently, chemical methods for protein reduction have been developed and have attracted much attention. In this review, we focus on the latest progress of chemical methods that knock down amyloid proteins, including the proteolysis-targeting chimera (PROTAC strategy, the “recognition-cleavage” strategy, the chaperone-mediated autophagy (CMA strategy, the selectively light-activatable organic and inorganic molecules strategy and other chemical strategies.

  8. Comparison of protein extraction methods suitable for proteomics ...

    African Journals Online (AJOL)

    Jane

    2011-07-27

    Jul 27, 2011 ... An efficient protein extraction method is a prerequisite for successful implementation of proteomics. ... research, it is noteworthy to discover a proteome ..... Proteomic analysis of rice (Oryza sativa) seeds during germination.

  9. DiffSLC: A graph centrality method to detect essential proteins of a protein-protein interaction network.

    Science.gov (United States)

    Mistry, Divya; Wise, Roger P; Dickerson, Julie A

    2017-01-01

    Identification of central genes and proteins in biomolecular networks provides credible candidates for pathway analysis, functional analysis, and essentiality prediction. The DiffSLC centrality measure predicts central and essential genes and proteins using a protein-protein interaction network. Network centrality measures prioritize nodes and edges based on their importance to the network topology. These measures helped identify critical genes and proteins in biomolecular networks. The proposed centrality measure, DiffSLC, combines the number of interactions of a protein and the gene coexpression values of genes from which those proteins were translated, as a weighting factor to bias the identification of essential proteins in a protein interaction network. Potentially essential proteins with low node degree are promoted through eigenvector centrality. Thus, the gene coexpression values are used in conjunction with the eigenvector of the network's adjacency matrix and edge clustering coefficient to improve essentiality prediction. The outcome of this prediction is shown using three variations: (1) inclusion or exclusion of gene co-expression data, (2) impact of different coexpression measures, and (3) impact of different gene expression data sets. For a total of seven networks, DiffSLC is compared to other centrality measures using Saccharomyces cerevisiae protein interaction networks and gene expression data. Comparisons are also performed for the top ranked proteins against the known essential genes from the Saccharomyces Gene Deletion Project, which show that DiffSLC detects more essential proteins and has a higher area under the ROC curve than other compared methods. This makes DiffSLC a stronger alternative to other centrality methods for detecting essential genes using a protein-protein interaction network that obeys centrality-lethality principle. DiffSLC is implemented using the igraph package in R, and networkx package in Python. The python package can be

  10. Rapid Determination of Protein Solubility and Stability Conditions for NMR Studies Using Incomplete Factorial Design

    International Nuclear Information System (INIS)

    Ducat, Thierry; Declerck, Nathalie; Gostan, Thierry; Kochoyan, Michel; Demene, Helene

    2006-01-01

    Sample preparation constitutes a crucial and limiting step in structural studies of proteins by NMR. The determination of the solubility and stability (SAS) conditions of biomolecules at millimolar concentrations stays today empirical and hence time- and material-consuming. Only few studies have been recently done in this field and they have highlighted the interest of using crystallogenesis tools to optimise sample conditions. In this study, we have adapted a method based on incomplete factorial design and making use of crystallisation plates to quantify the influence of physico-chemical parameters such as buffer pH and salts on protein SAS. A description of the experimental set up and an evaluation of the method are given by case studies on two functional domains from the bacterial regulatory protein LicT as well as two other proteins. Using this method, we could rapidly determine optimised conditions for extracting soluble proteins from bacterial cells and for preparing purified protein samples sufficiently concentrated and stable for NMR characterisation. The drastic reduction in the time and number of experiments required for searching protein SAS conditions makes this method particularly well-adapted for a systematic investigation on a large range of physico-chemical parameters

  11. Annotating Mutational Effects on Proteins and Protein Interactions: Designing Novel and Revisiting Existing Protocols.

    Science.gov (United States)

    Li, Minghui; Goncearenco, Alexander; Panchenko, Anna R

    2017-01-01

    In this review we describe a protocol to annotate the effects of missense mutations on proteins, their functions, stability, and binding. For this purpose we present a collection of the most comprehensive databases which store different types of sequencing data on missense mutations, we discuss their relationships, possible intersections, and unique features. Next, we suggest an annotation workflow using the state-of-the art methods and highlight their usability, advantages, and limitations for different cases. Finally, we address a particularly difficult problem of deciphering the molecular mechanisms of mutations on proteins and protein complexes to understand the origins and mechanisms of diseases.

  12. Efficient protein production method for NMR using soluble protein tags with cold shock expression vector

    International Nuclear Information System (INIS)

    Hayashi, Kokoro; Kojima, Chojiro

    2010-01-01

    The E. coli protein expression system is one of the most useful methods employed for NMR sample preparation. However, the production of some recombinant proteins in E. coli is often hampered by difficulties such as low expression level and low solubility. To address these problems, a modified cold-shock expression system containing a glutathione S-transferase (GST) tag, the pCold-GST system, was investigated. The pCold-GST system successfully expressed 9 out of 10 proteins that otherwise could not be expressed using a conventional E. coli expression system. Here, we applied the pCold-GST system to 84 proteins and 78 proteins were successfully expressed in the soluble fraction. Three other cold-shock expression systems containing a maltose binding protein tag (pCold-MBP), protein G B1 domain tag (pCold-GB1) or thioredoxin tag (pCold-Trx) were also developed to improve the yield. Additionally, we show that a C-terminal proline tag, which is invisible in 1 H- 15 N HSQC spectra, inhibits protein degradation and increases the final yield of unstable proteins. The purified proteins were amenable to NMR analyses. These data suggest that pCold expression systems combined with soluble protein tags can be utilized to improve the expression and purification of various proteins for NMR analysis.

  13. Efficient protein production method for NMR using soluble protein tags with cold shock expression vector

    Energy Technology Data Exchange (ETDEWEB)

    Hayashi, Kokoro [Fujifilm Corporation, Analysis Technology Center (Japan); Kojima, Chojiro, E-mail: kojima@protein.osaka-u.ac.j [Nara Institute of Science and Technology (NAIST), Graduate School of Biological Sciences (Japan)

    2010-11-15

    The E. coli protein expression system is one of the most useful methods employed for NMR sample preparation. However, the production of some recombinant proteins in E. coli is often hampered by difficulties such as low expression level and low solubility. To address these problems, a modified cold-shock expression system containing a glutathione S-transferase (GST) tag, the pCold-GST system, was investigated. The pCold-GST system successfully expressed 9 out of 10 proteins that otherwise could not be expressed using a conventional E. coli expression system. Here, we applied the pCold-GST system to 84 proteins and 78 proteins were successfully expressed in the soluble fraction. Three other cold-shock expression systems containing a maltose binding protein tag (pCold-MBP), protein G B1 domain tag (pCold-GB1) or thioredoxin tag (pCold-Trx) were also developed to improve the yield. Additionally, we show that a C-terminal proline tag, which is invisible in {sup 1}H-{sup 15}N HSQC spectra, inhibits protein degradation and increases the final yield of unstable proteins. The purified proteins were amenable to NMR analyses. These data suggest that pCold expression systems combined with soluble protein tags can be utilized to improve the expression and purification of various proteins for NMR analysis.

  14. Three-dimensional protein structure prediction: Methods and computational strategies.

    Science.gov (United States)

    Dorn, Márcio; E Silva, Mariel Barbachan; Buriol, Luciana S; Lamb, Luis C

    2014-10-12

    A long standing problem in structural bioinformatics is to determine the three-dimensional (3-D) structure of a protein when only a sequence of amino acid residues is given. Many computational methodologies and algorithms have been proposed as a solution to the 3-D Protein Structure Prediction (3-D-PSP) problem. These methods can be divided in four main classes: (a) first principle methods without database information; (b) first principle methods with database information; (c) fold recognition and threading methods; and (d) comparative modeling methods and sequence alignment strategies. Deterministic computational techniques, optimization techniques, data mining and machine learning approaches are typically used in the construction of computational solutions for the PSP problem. Our main goal with this work is to review the methods and computational strategies that are currently used in 3-D protein prediction. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Assessing the accuracy of ancestral protein reconstruction methods.

    Directory of Open Access Journals (Sweden)

    Paul D Williams

    2006-06-01

    Full Text Available The phylogenetic inference of ancestral protein sequences is a powerful technique for the study of molecular evolution, but any conclusions drawn from such studies are only as good as the accuracy of the reconstruction method. Every inference method leads to errors in the ancestral protein sequence, resulting in potentially misleading estimates of the ancestral protein's properties. To assess the accuracy of ancestral protein reconstruction methods, we performed computational population evolution simulations featuring near-neutral evolution under purifying selection, speciation, and divergence using an off-lattice protein model where fitness depends on the ability to be stable in a specified target structure. We were thus able to compare the thermodynamic properties of the true ancestral sequences with the properties of "ancestral sequences" inferred by maximum parsimony, maximum likelihood, and Bayesian methods. Surprisingly, we found that methods such as maximum parsimony and maximum likelihood that reconstruct a "best guess" amino acid at each position overestimate thermostability, while a Bayesian method that sometimes chooses less-probable residues from the posterior probability distribution does not. Maximum likelihood and maximum parsimony apparently tend to eliminate variants at a position that are slightly detrimental to structural stability simply because such detrimental variants are less frequent. Other properties of ancestral proteins might be similarly overestimated. This suggests that ancestral reconstruction studies require greater care to come to credible conclusions regarding functional evolution. Inferred functional patterns that mimic reconstruction bias should be reevaluated.

  16. Assessing the accuracy of ancestral protein reconstruction methods.

    Science.gov (United States)

    Williams, Paul D; Pollock, David D; Blackburne, Benjamin P; Goldstein, Richard A

    2006-06-23

    The phylogenetic inference of ancestral protein sequences is a powerful technique for the study of molecular evolution, but any conclusions drawn from such studies are only as good as the accuracy of the reconstruction method. Every inference method leads to errors in the ancestral protein sequence, resulting in potentially misleading estimates of the ancestral protein's properties. To assess the accuracy of ancestral protein reconstruction methods, we performed computational population evolution simulations featuring near-neutral evolution under purifying selection, speciation, and divergence using an off-lattice protein model where fitness depends on the ability to be stable in a specified target structure. We were thus able to compare the thermodynamic properties of the true ancestral sequences with the properties of "ancestral sequences" inferred by maximum parsimony, maximum likelihood, and Bayesian methods. Surprisingly, we found that methods such as maximum parsimony and maximum likelihood that reconstruct a "best guess" amino acid at each position overestimate thermostability, while a Bayesian method that sometimes chooses less-probable residues from the posterior probability distribution does not. Maximum likelihood and maximum parsimony apparently tend to eliminate variants at a position that are slightly detrimental to structural stability simply because such detrimental variants are less frequent. Other properties of ancestral proteins might be similarly overestimated. This suggests that ancestral reconstruction studies require greater care to come to credible conclusions regarding functional evolution. Inferred functional patterns that mimic reconstruction bias should be reevaluated.

  17. Improving protein function prediction methods with integrated literature data

    Directory of Open Access Journals (Sweden)

    Gabow Aaron P

    2008-04-01

    Full Text Available Abstract Background Determining the function of uncharacterized proteins is a major challenge in the post-genomic era due to the problem's complexity and scale. Identifying a protein's function contributes to an understanding of its role in the involved pathways, its suitability as a drug target, and its potential for protein modifications. Several graph-theoretic approaches predict unidentified functions of proteins by using the functional annotations of better-characterized proteins in protein-protein interaction networks. We systematically consider the use of literature co-occurrence data, introduce a new method for quantifying the reliability of co-occurrence and test how performance differs across species. We also quantify changes in performance as the prediction algorithms annotate with increased specificity. Results We find that including information on the co-occurrence of proteins within an abstract greatly boosts performance in the Functional Flow graph-theoretic function prediction algorithm in yeast, fly and worm. This increase in performance is not simply due to the presence of additional edges since supplementing protein-protein interactions with co-occurrence data outperforms supplementing with a comparably-sized genetic interaction dataset. Through the combination of protein-protein interactions and co-occurrence data, the neighborhood around unknown proteins is quickly connected to well-characterized nodes which global prediction algorithms can exploit. Our method for quantifying co-occurrence reliability shows superior performance to the other methods, particularly at threshold values around 10% which yield the best trade off between coverage and accuracy. In contrast, the traditional way of asserting co-occurrence when at least one abstract mentions both proteins proves to be the worst method for generating co-occurrence data, introducing too many false positives. Annotating the functions with greater specificity is harder

  18. Engineering Designed Proteins for Light Capture, Energy Transfer, and Emissive Sensing In Vivo

    Science.gov (United States)

    Mancini, Joshua A.

    Proteins that are used for photosynthetic light harvesting and biological signaling are critical to life. These types of proteins act as scaffolds that hold small, sometimes metal-containing organic molecules in precise locations for light absorption and successive use. For signaling proteins, this energy can be used to induce a photoisomerization of the small molecule that can turn on or off a signaling cascade that controls the physiology of an organism. Alternatively, photosynthetic light-harvesting proteins funnel this energy in a directional manner towards a charge separating catalytic component that can change this light energy into chemical energy. The protein environment also serves to tune the photophysical properties of the small molecules. This is seen extensively with the linear tetrapyrroles that are used in both photosynthetic and signaling proteins. Many efforts have been made to harness these natural proteins for societal use, including improving photophysical properties and interfacing capabilities with manmade catalytic components. Several methods of achieving improvement have entailed structurally guided mutation and directed evolution. However, these methods all have their limitations due to the inherent complexity and fragility of the natural proteins. This work presents an alternative more robust method to natural proteins. My thesis states: that man-made proteins, known as maquettes, employing basic rules of protein folding, can be designed to become light harvesting and signaling proteins that can be assembled fully in vivo providing an alternative, robust, and versatile platform for meeting the diverse array of societal "green chemistry" and biomedical needs. This in vivo assembly is carried out by interacting with cyanobacterial protein and pigment machinery, both as stand-alone units and as protein fusions with natural antenna complexes. Additionally, this work offers insight for fast and tight binding of circular and linear tetrapyrroles

  19. New method of design of nonimaging concentrators.

    Science.gov (United States)

    Miñano, J C; González, J C

    1992-06-01

    A new method of designing nonimaging concentrators is presented and two new types of concentrators are developed. The first is an aspheric lens, and the second is a lens-mirror combination. A ray tracing of three-dimensional concentrators (with rotational symmetry) is also done, showing that the lens-mirror combination has a total transmission as high as that of the full compound parabolic concentrators, while their depth is much smaller than the classical parabolic mirror-nonimaging concentrator combinations. Another important feature of this concentrator is that the optically active surfaces are not in contact with the receiver, as occurs in other nonimaging concentrators in which the rim of the mirror coincides with the rim of the receiver.

  20. Optical design teaching by computing graphic methods

    Science.gov (United States)

    Vazquez-Molini, D.; Muñoz-Luna, J.; Fernandez-Balbuena, A. A.; Garcia-Botella, A.; Belloni, P.; Alda, J.

    2012-10-01

    One of the key challenges in the teaching of Optics is that students need to know not only the math of the optical design, but also, and more important, to grasp and understand the optics in a three-dimensional space. Having a clear image of the problem to solve is the first step in order to begin to solve that problem. Therefore to achieve that the students not only must know the equation of refraction law but they have also to understand how the main parameters of this law are interacting among them. This should be a major goal in the teaching course. Optical graphic methods are a valuable tool in this way since they have the advantage of visual information and the accuracy of a computer calculation.

  1. Research and Design of Rootkit Detection Method

    Science.gov (United States)

    Liu, Leian; Yin, Zuanxing; Shen, Yuli; Lin, Haitao; Wang, Hongjiang

    Rootkit is one of the most important issues of network communication systems, which is related to the security and privacy of Internet users. Because of the existence of the back door of the operating system, a hacker can use rootkit to attack and invade other people's computers and thus he can capture passwords and message traffic to and from these computers easily. With the development of the rootkit technology, its applications are more and more extensive and it becomes increasingly difficult to detect it. In addition, for various reasons such as trade secrets, being difficult to be developed, and so on, the rootkit detection technology information and effective tools are still relatively scarce. In this paper, based on the in-depth analysis of the rootkit detection technology, a new kind of the rootkit detection structure is designed and a new method (software), X-Anti, is proposed. Test results show that software designed based on structure proposed is much more efficient than any other rootkit detection software.

  2. Decomposition of overlapping protein complexes: A graph theoretical method for analyzing static and dynamic protein associations

    Directory of Open Access Journals (Sweden)

    Guimarães Katia S

    2006-04-01

    Full Text Available Abstract Background Most cellular processes are carried out by multi-protein complexes, groups of proteins that bind together to perform a specific task. Some proteins form stable complexes, while other proteins form transient associations and are part of several complexes at different stages of a cellular process. A better understanding of this higher-order organization of proteins into overlapping complexes is an important step towards unveiling functional and evolutionary mechanisms behind biological networks. Results We propose a new method for identifying and representing overlapping protein complexes (or larger units called functional groups within a protein interaction network. We develop a graph-theoretical framework that enables automatic construction of such representation. We illustrate the effectiveness of our method by applying it to TNFα/NF-κB and pheromone signaling pathways. Conclusion The proposed representation helps in understanding the transitions between functional groups and allows for tracking a protein's path through a cascade of functional groups. Therefore, depending on the nature of the network, our representation is capable of elucidating temporal relations between functional groups. Our results show that the proposed method opens a new avenue for the analysis of protein interaction networks.

  3. Hot spot-based design of small-molecule inhibitors for protein-protein interactions.

    Science.gov (United States)

    Guo, Wenxing; Wisniewski, John A; Ji, Haitao

    2014-06-01

    Protein-protein interactions (PPIs) are important targets for the development of chemical probes and therapeutic agents. From the initial discovery of the existence of hot spots at PPI interfaces, it has been proposed that hot spots might provide the key for developing small-molecule PPI inhibitors. However, there has been no review on the ways in which the knowledge of hot spots can be used to achieve inhibitor design, nor critical examination of successful examples. This Digest discusses the characteristics of hot spots and the identification of druggable hot spot pockets. An analysis of four examples of hot spot-based design reveals the importance of this strategy in discovering potent and selective PPI inhibitors. A general procedure for hot spot-based design of PPI inhibitors is outlined. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Design Methods in the Emergent City

    DEFF Research Database (Denmark)

    Samson, Kristine

    The paper seeks to define urban design in relation to the specific challenges of emerging cities. Through a case study of Mudo Coletivos temporary structure, Bolha Imobiliaria, and the making of it, I wish to outline a design approach for urban design in cities lacking public spaces. Urban design...... is understood in a broad sense, not as architectural design but as spatial design and artistic interventions in public space. Through the paper I will address how the designer can co-create and reassemble existing urban spaces through design acts. The approach suggests a situated design methodology but is based...... on a theoretical understanding. It is my belief that the designer, by looking into the emergent properties of urban spaces, instead of its physical and cartographical outlines, can see her work as a processual intervention in the city rather than durable object design....

  5. Protein structure recognition: From eigenvector analysis to structural threading method

    Science.gov (United States)

    Cao, Haibo

    In this work, we try to understand the protein folding problem using pair-wise hydrophobic interaction as the dominant interaction for the protein folding process. We found a strong correlation between amino acid sequence and the corresponding native structure of the protein. Some applications of this correlation were discussed in this dissertation include the domain partition and a new structural threading method as well as the performance of this method in the CASP5 competition. In the first part, we give a brief introduction to the protein folding problem. Some essential knowledge and progress from other research groups was discussed. This part include discussions of interactions among amino acids residues, lattice HP model, and the designablity principle. In the second part, we try to establish the correlation between amino acid sequence and the corresponding native structure of the protein. This correlation was observed in our eigenvector study of protein contact matrix. We believe the correlation is universal, thus it can be used in automatic partition of protein structures into folding domains. In the third part, we discuss a threading method based on the correlation between amino acid sequence and ominant eigenvector of the structure contact-matrix. A mathematically straightforward iteration scheme provides a self-consistent optimum global sequence-structure alignment. The computational efficiency of this method makes it possible to search whole protein structure databases for structural homology without relying on sequence similarity. The sensitivity and specificity of this method is discussed, along with a case of blind test prediction. In the appendix, we list the overall performance of this threading method in CASP5 blind test in comparison with other existing approaches.

  6. Orientation-dependent backbone-only residue pair scoring functions for fixed backbone protein design

    Directory of Open Access Journals (Sweden)

    Bordner Andrew J

    2010-04-01

    Full Text Available Abstract Background Empirical scoring functions have proven useful in protein structure modeling. Most such scoring functions depend on protein side chain conformations. However, backbone-only scoring functions do not require computationally intensive structure optimization and so are well suited to protein design, which requires fast score evaluation. Furthermore, scoring functions that account for the distinctive relative position and orientation preferences of residue pairs are expected to be more accurate than those that depend only on the separation distance. Results Residue pair scoring functions for fixed backbone protein design were derived using only backbone geometry. Unlike previous studies that used spherical harmonics to fit 2D angular distributions, Gaussian Mixture Models were used to fit the full 3D (position only and 6D (position and orientation distributions of residue pairs. The performance of the 1D (residue separation only, 3D, and 6D scoring functions were compared by their ability to identify correct threading solutions for a non-redundant benchmark set of protein backbone structures. The threading accuracy was found to steadily increase with increasing dimension, with the 6D scoring function achieving the highest accuracy. Furthermore, the 3D and 6D scoring functions were shown to outperform side chain-dependent empirical potentials from three other studies. Next, two computational methods that take advantage of the speed and pairwise form of these new backbone-only scoring functions were investigated. The first is a procedure that exploits available sequence data by averaging scores over threading solutions for homologs. This was evaluated by applying it to the challenging problem of identifying interacting transmembrane alpha-helices and found to further improve prediction accuracy. The second is a protein design method for determining the optimal sequence for a backbone structure by applying Belief Propagation

  7. Staining Method for Protein Analysis by Capillary Gel Electrophoresis

    Science.gov (United States)

    Wu, Shuqing; Lu, Joann J; Wang, Shili; Peck, Kristy L.; Li, Guigen; Liu, Shaorong

    2009-01-01

    A novel staining method and the associated fluorescent dye were developed for protein analysis by capillary SDS-PAGE. The method strategy is to synthesize a pseudo-SDS dye and use it to replace some of the SDS in SDS–protein complexes so that the protein can be fluorescently detected. The pseudo-SDS dye consists of a long, straight alkyl chain connected to a negative charged fluorescent head and binds to proteins just as SDS. The number of dye molecules incorporated with a protein depends on the dye concentration relative to SDS in the sample solution, since SDS and dye bind to proteins competitively. In this work, we synthesized a series of pseudo-SDS dyes, and tested their performances for capillary SDS-PAGE. FT-16 (a fluorescein molecule linked with a hexadodecyl group) seemed to be the best among all the dyes tested. Although the numbers of dye molecules bound to proteins (and the fluorescence signals from these protein complexes) were maximized in the absence of SDS, high-quality separations were obtained when co-complexes of SDS–protein–dye were formed. The migration time correlates well with protein size even after some of the SDS in the SDS–protein complexes was replaced by the pseudo-SDS dye. Under optimized experimental conditions and using a laser-induced fluorescence detector, limits of detection of as low as 0.13 ng/mL (bovine serum albumin) and dynamic ranges over 5 orders of magnitude in which fluorescence response is proportional to the square root of analyte concentration were obtained. The method and dye were also tested for separations of real-world samples from E. coli. PMID:17874848

  8. Designing sequence to control protein function in an EF-hand protein.

    Science.gov (United States)

    Bunick, Christopher G; Nelson, Melanie R; Mangahas, Sheryll; Hunter, Michael J; Sheehan, Jonathan H; Mizoue, Laura S; Bunick, Gerard J; Chazin, Walter J

    2004-05-19

    The extent of conformational change that calcium binding induces in EF-hand proteins is a key biochemical property specifying Ca(2+) sensor versus signal modulator function. To understand how differences in amino acid sequence lead to differences in the response to Ca(2+) binding, comparative analyses of sequence and structures, combined with model building, were used to develop hypotheses about which amino acid residues control Ca(2+)-induced conformational changes. These results were used to generate a first design of calbindomodulin (CBM-1), a calbindin D(9k) re-engineered with 15 mutations to respond to Ca(2+) binding with a conformational change similar to that of calmodulin. The gene for CBM-1 was synthesized, and the protein was expressed and purified. Remarkably, this protein did not exhibit any non-native-like molten globule properties despite the large number of mutations and the nonconservative nature of some of them. Ca(2+)-induced changes in CD intensity and in the binding of the hydrophobic probe, ANS, implied that CBM-1 does undergo Ca(2+) sensorlike conformational changes. The X-ray crystal structure of Ca(2+)-CBM-1 determined at 1.44 A resolution reveals the anticipated increase in hydrophobic surface area relative to the wild-type protein. A nascent calmodulin-like hydrophobic docking surface was also found, though it is occluded by the inter-EF-hand loop. The results from this first calbindomodulin design are discussed in terms of progress toward understanding the relationships between amino acid sequence, protein structure, and protein function for EF-hand CaBPs, as well as the additional mutations for the next CBM design.

  9. Mean protein evolutionary distance: a method for comparative protein evolution and its application.

    Directory of Open Access Journals (Sweden)

    Michael J Wise

    Full Text Available Proteins are under tight evolutionary constraints, so if a protein changes it can only do so in ways that do not compromise its function. In addition, the proteins in an organism evolve at different rates. Leveraging the history of patristic distance methods, a new method for analysing comparative protein evolution, called Mean Protein Evolutionary Distance (MeaPED, measures differential resistance to evolutionary pressure across viral proteomes and is thereby able to point to the proteins' roles. Different species' proteomes can also be compared because the results, consistent across virus subtypes, concisely reflect the very different lifestyles of the viruses. The MeaPED method is here applied to influenza A virus, hepatitis C virus, human immunodeficiency virus (HIV, dengue virus, rotavirus A, polyomavirus BK and measles, which span the positive and negative single-stranded, doubled-stranded and reverse transcribing RNA viruses, and double-stranded DNA viruses. From this analysis, host interaction proteins including hemagglutinin (influenza, and viroporins agnoprotein (polyomavirus, p7 (hepatitis C and VPU (HIV emerge as evolutionary hot-spots. By contrast, RNA-directed RNA polymerase proteins including L (measles, PB1/PB2 (influenza and VP1 (rotavirus, and internal serine proteases such as NS3 (dengue and hepatitis C virus emerge as evolutionary cold-spots. The hot spot influenza hemagglutinin protein is contrasted with the related cold spot H protein from measles. It is proposed that evolutionary cold-spot proteins can become significant targets for second-line anti-viral therapeutics, in cases where front-line vaccines are not available or have become ineffective due to mutations in the hot-spot, generally more antigenically exposed proteins. The MeaPED package is available from www.pam1.bcs.uwa.edu.au/~michaelw/ftp/src/meaped.tar.gz.

  10. Mean protein evolutionary distance: a method for comparative protein evolution and its application.

    Science.gov (United States)

    Wise, Michael J

    2013-01-01

    Proteins are under tight evolutionary constraints, so if a protein changes it can only do so in ways that do not compromise its function. In addition, the proteins in an organism evolve at different rates. Leveraging the history of patristic distance methods, a new method for analysing comparative protein evolution, called Mean Protein Evolutionary Distance (MeaPED), measures differential resistance to evolutionary pressure across viral proteomes and is thereby able to point to the proteins' roles. Different species' proteomes can also be compared because the results, consistent across virus subtypes, concisely reflect the very different lifestyles of the viruses. The MeaPED method is here applied to influenza A virus, hepatitis C virus, human immunodeficiency virus (HIV), dengue virus, rotavirus A, polyomavirus BK and measles, which span the positive and negative single-stranded, doubled-stranded and reverse transcribing RNA viruses, and double-stranded DNA viruses. From this analysis, host interaction proteins including hemagglutinin (influenza), and viroporins agnoprotein (polyomavirus), p7 (hepatitis C) and VPU (HIV) emerge as evolutionary hot-spots. By contrast, RNA-directed RNA polymerase proteins including L (measles), PB1/PB2 (influenza) and VP1 (rotavirus), and internal serine proteases such as NS3 (dengue and hepatitis C virus) emerge as evolutionary cold-spots. The hot spot influenza hemagglutinin protein is contrasted with the related cold spot H protein from measles. It is proposed that evolutionary cold-spot proteins can become significant targets for second-line anti-viral therapeutics, in cases where front-line vaccines are not available or have become ineffective due to mutations in the hot-spot, generally more antigenically exposed proteins. The MeaPED package is available from www.pam1.bcs.uwa.edu.au/~michaelw/ftp/src/meaped.tar.gz.

  11. A SIMPLE FLUORESCENT LABELING METHOD FOR STUDIES OF PROTEIN OXIDATION, PROTEIN MODIFICATION, AND PROTEOLYSIS

    Science.gov (United States)

    Pickering, Andrew. M.; Davies, Kelvin. J. A.

    2014-01-01

    Proteins are sensitive to oxidation, and oxidized proteins are excellent substrates for degradation by proteolytic enzymes such as the Proteasome and the mitochondrial Lon protease. Protein labeling is required for studies of protein turnover. Unfortunately, most labeling techniques involve 3H or 14C methylation which is expensive, exposes researchers to radioactivity, generates large amounts of radioactive waste, and allows only single-point assays because samples require acid-precipitation. Alternative labeling methods, have largely proven unsuitable, either because the probe itself is modified by the oxidant(s) being studied, or because the alternative labeling techniques are too complex or too costly for routine use. What is needed is a simple, quick, and cheap labeling technique that uses a non-radioactive marker, that binds strongly to proteins, is resistant to oxidative modification, and emits a strong signal. We have devised a new reductive method for labeling free carboxyl groups of proteins with the small fluorophore 7-amino-4-methycoumarin (AMC). When bound to target proteins, AMC fluoresces very weakly but when AMC is released by proteinases, proteases, or peptidases, it fluoresces strongly. Thus, without acid-precipitation, the proteolysis of any target protein can be studied continuously, in multiwell plates. In direct comparisons, 3H-labeled proteins and AMC-labeled proteins exhibited essentially identical degradation patterns during incubation with trypsin, cell extracts, and purified proteasome. AMC-labeled proteins are well-suited to study increased proteolytic susceptibility following protein modification, since the AMC-protein bond is resistant to oxidizing agents such as hydrogen peroxide and peroxynitrite, and is stable over time and to extremes of pH, temperature (even boiling), freeze-thawing, mercaptoethanol, and methanol. PMID:21988844

  12. A method for fast energy estimation and visualization of protein-ligand interaction

    Science.gov (United States)

    Tomioka, Nobuo; Itai, Akiko; Iitaka, Yoichi

    1987-10-01

    A new computational and graphical method for facilitating ligand-protein docking studies is developed on a three-dimensional computer graphics display. Various physical and chemical properties inside the ligand binding pocket of a receptor protein, whose structure is elucidated by X-ray crystal analysis, are calculated on three-dimensional grid points and are stored in advance. By utilizing those tabulated data, it is possible to estimate the non-bonded and electrostatic interaction energy and the number of possible hydrogen bonds between protein and ligand molecules in real time during an interactive docking operation. The method also provides a comprehensive visualization of the local environment inside the binding pocket. With this method, it becomes easier to find a roughly stable geometry of ligand molecules, and one can therefore make a rapid survey of the binding capability of many drug candidates. The method will be useful for drug design as well as for the examination of protein-ligand interactions.

  13. Computational methods for protein identification from mass spectrometry data.

    Directory of Open Access Journals (Sweden)

    Leo McHugh

    2008-02-01

    Full Text Available Protein identification using mass spectrometry is an indispensable computational tool in the life sciences. A dramatic increase in the use of proteomic strategies to understand the biology of living systems generates an ongoing need for more effective, efficient, and accurate computational methods for protein identification. A wide range of computational methods, each with various implementations, are available to complement different proteomic approaches. A solid knowledge of the range of algorithms available and, more critically, the accuracy and effectiveness of these techniques is essential to ensure as many of the proteins as possible, within any particular experiment, are correctly identified. Here, we undertake a systematic review of the currently available methods and algorithms for interpreting, managing, and analyzing biological data associated with protein identification. We summarize the advances in computational solutions as they have responded to corresponding advances in mass spectrometry hardware. The evolution of scoring algorithms and metrics for automated protein identification are also discussed with a focus on the relative performance of different techniques. We also consider the relative advantages and limitations of different techniques in particular biological contexts. Finally, we present our perspective on future developments in the area of computational protein identification by considering the most recent literature on new and promising approaches to the problem as well as identifying areas yet to be explored and the potential application of methods from other areas of computational biology.

  14. Core design methods for advanced LMFBRs

    International Nuclear Information System (INIS)

    Chandler, J.C.; Marr, D.R.; McCurry, D.C.; Cantley, D.A.

    1977-05-01

    The multidiscipline approach to advanced LMFBR core design requires an iterative design procedure to obtain a closely-coupled design. HEDL's philosophy requires that the designs should be coupled to the extent that the design limiting fuel pin, the design limiting duct and the core reactivity lifetime should all be equal and should equal the fuel residence time. The design procedure consists of an iterative loop involving three stages of the design sequence. Stage 1 consists of general mechanical design and reactor physics scoping calculations to arrive at an initial core layout. Stage 2 consists of detailed reactor physics calculations for the core configuration arrived at in Stage 1. Based upon the detailed reactor physics results, a decision is made either to alter the design (Stage 1) or go to Stage 3. Stage 3 consists of core orificing and detailed component mechanical design calculations. At this point, an assessment is made regarding design adequacy. If the design is inadequate the entire procedure is repeated until the design is acceptable

  15. In vivo cellular imaging using fluorescent proteins - Methods and Protocols

    Directory of Open Access Journals (Sweden)

    M. Monti

    2012-12-01

    Full Text Available The discovery and genetic engineering of fluorescent proteins has revolutionized cell biology. What was previously invisible to the cell often can be made visible with the use of fluorescent proteins. With this words, Robert M. Hoffman introduces In vivo Cellular Imaging Using Fluorescent proteins, the eighteen chapters book dedicated to the description of how fluorescence proteins have changed the way to analyze cellular processes in vivo. Modern researches aim to study new and less invasive methods able to follow the behavior of different cell types in different biological contexts: for example, how cancer cells migrate or how they respond to different therapies. Also, in vivo systems can help researchers to better understand animal embryonic development so as how fluorescence proteins may be used to monitor different processes in living organisms at the molecular and cellular level.

  16. Using the clustered circular layout as an informative method for visualizing protein-protein interaction networks.

    Science.gov (United States)

    Fung, David C Y; Wilkins, Marc R; Hart, David; Hong, Seok-Hee

    2010-07-01

    The force-directed layout is commonly used in computer-generated visualizations of protein-protein interaction networks. While it is good for providing a visual outline of the protein complexes and their interactions, it has two limitations when used as a visual analysis method. The first is poor reproducibility. Repeated running of the algorithm does not necessarily generate the same layout, therefore, demanding cognitive readaptation on the investigator's part. The second limitation is that it does not explicitly display complementary biological information, e.g. Gene Ontology, other than the protein names or gene symbols. Here, we present an alternative layout called the clustered circular layout. Using the human DNA replication protein-protein interaction network as a case study, we compared the two network layouts for their merits and limitations in supporting visual analysis.

  17. Integrating protein engineering with process design for biocatalysis

    DEFF Research Database (Denmark)

    Woodley, John M.

    2017-01-01

    Biocatalysis uses enzymes for chemical synthesis and production, offering selective, safe and sustainable catalysis. While today the majority of applications are in the pharmaceutical sector, new opportunities are arising every day in other industry sectors, where production costs become a more...... important driver. In the early applications of the technology, it was necessary to design processes to match the properties of the biocatalyst. With the advent of protein engineering, organic chemists started to develop and improve enzymes to suit their needs. Likewise in industry, although not widespread......, a new paradigm was already implemented several years ago to engineer enzymes to suit process needs. Today, a new era is entered, where the effectiveness with which such integrated protein and process engineering is achieved becomes critical to implementation. In this paper, the development of a tool...

  18. Educating Instructional Designers: Different Methods for Different Outcomes.

    Science.gov (United States)

    Rowland, Gordon; And Others

    1994-01-01

    Suggests new methods of teaching instructional design based on literature reviews of other design fields including engineering, architecture, interior design, media design, and medicine. Methods discussed include public presentations, visiting experts, competitions, artifacts, case studies, design studios, and internships and apprenticeships.…

  19. Design principles for cancer therapy guided by changes in complexity of protein-protein interaction networks.

    Science.gov (United States)

    Benzekry, Sebastian; Tuszynski, Jack A; Rietman, Edward A; Lakka Klement, Giannoula

    2015-05-28

    The ever-increasing expanse of online bioinformatics data is enabling new ways to, not only explore the visualization of these data, but also to apply novel mathematical methods to extract meaningful information for clinically relevant analysis of pathways and treatment decisions. One of the methods used for computing topological characteristics of a space at different spatial resolutions is persistent homology. This concept can also be applied to network theory, and more specifically to protein-protein interaction networks, where the number of rings in an individual cancer network represents a measure of complexity. We observed a linear correlation of R = -0.55 between persistent homology and 5-year survival of patients with a variety of cancers. This relationship was used to predict the proteins within a protein-protein interaction network with the most impact on cancer progression. By re-computing the persistent homology after computationally removing an individual node (protein) from the protein-protein interaction network, we were able to evaluate whether such an inhibition would lead to improvement in patient survival. The power of this approach lied in its ability to identify the effects of inhibition of multiple proteins and in the ability to expose whether the effect of a single inhibition may be amplified by inhibition of other proteins. More importantly, we illustrate specific examples of persistent homology calculations, which correctly predict the survival benefit observed effects in clinical trials using inhibitors of the identified molecular target. We propose that computational approaches such as persistent homology may be used in the future for selection of molecular therapies in clinic. The technique uses a mathematical algorithm to evaluate the node (protein) whose inhibition has the highest potential to reduce network complexity. The greater the drop in persistent homology, the greater reduction in network complexity, and thus a larger

  20. Efficient Design Methods for Embedded Communication Systems

    Directory of Open Access Journals (Sweden)

    Holzer M

    2006-01-01

    Full Text Available Nowadays, design of embedded systems is confronted with complex signal processing algorithms and a multitude of computational intensive multimedia applications, while time to product launch has been extremely reduced. Especially in the wireless domain, those challenges are stacked with tough requirements on power consumption and chip size. Unfortunately, design productivity did not undergo a similar progression, and therefore fails to cope with the heterogeneity of modern architectures. Electronic design automation tools exhibit deep gaps in the design flow like high-level characterization of algorithms, floating-point to fixed-point conversion, hardware/software partitioning, and virtual prototyping. This tutorial paper surveys several promising approaches to solve the widespread design problems in this field. An overview over consistent design methodologies that establish a framework for connecting the different design tasks is given. This is followed by a discussion of solutions for the integrated automation of specific design tasks.

  1. Formation of Giant Protein Vesicles by a Lipid Cosolvent Method

    DEFF Research Database (Denmark)

    Hansen, Jesper S.; Vararattanavech, Ardcharaporn; Vissing, Thomas

    2011-01-01

    This paper describes a method to create giant protein vesicles (GPVs) of ≥10 μm by solvent‐driven fusion of large vesicles (0.1–0.2 μm) with reconstituted membrane proteins. We found that formation of GPVs proceeded from rotational mixing of protein‐reconstituted large unilamellar vesicles (LUVs)...... of spinach SoPIP2;1 and E. coli AqpZ aquaporins. Our findings show that hydrophobic interactions within the bilayer of formed GPVs are influenced not only by the solvent partitioning propensity, but also by lipid composition and membrane protein isoform....

  2. Spacecraft early design validation using formal methods

    International Nuclear Information System (INIS)

    Bozzano, Marco; Cimatti, Alessandro; Katoen, Joost-Pieter; Katsaros, Panagiotis; Mokos, Konstantinos; Nguyen, Viet Yen; Noll, Thomas; Postma, Bart; Roveri, Marco

    2014-01-01

    The size and complexity of software in spacecraft is increasing exponentially, and this trend complicates its validation within the context of the overall spacecraft system. Current validation methods are labor-intensive as they rely on manual analysis, review and inspection. For future space missions, we developed – with challenging requirements from the European space industry – a novel modeling language and toolset for a (semi-)automated validation approach. Our modeling language is a dialect of AADL and enables engineers to express the system, the software, and their reliability aspects. The COMPASS toolset utilizes state-of-the-art model checking techniques, both qualitative and probabilistic, for the analysis of requirements related to functional correctness, safety, dependability and performance. Several pilot projects have been performed by industry, with two of them having focused on the system-level of a satellite platform in development. Our efforts resulted in a significant advancement of validating spacecraft designs from several perspectives, using a single integrated system model. The associated technology readiness level increased from level 1 (basic concepts and ideas) to early level 4 (laboratory-tested)

  3. Global optimization methods for engineering design

    Science.gov (United States)

    Arora, Jasbir S.

    1990-01-01

    The problem is to find a global minimum for the Problem P. Necessary and sufficient conditions are available for local optimality. However, global solution can be assured only under the assumption of convexity of the problem. If the constraint set S is compact and the cost function is continuous on it, existence of a global minimum is guaranteed. However, in view of the fact that no global optimality conditions are available, a global solution can be found only by an exhaustive search to satisfy Inequality. The exhaustive search can be organized in such a way that the entire design space need not be searched for the solution. This way the computational burden is reduced somewhat. It is concluded that zooming algorithm for global optimizations appears to be a good alternative to stochastic methods. More testing is needed; a general, robust, and efficient local minimizer is required. IDESIGN was used in all numerical calculations which is based on a sequential quadratic programming algorithm, and since feasible set keeps on shrinking, a good algorithm to find an initial feasible point is required. Such algorithms need to be developed and evaluated.

  4. Identifying Hierarchical and Overlapping Protein Complexes Based on Essential Protein-Protein Interactions and “Seed-Expanding” Method

    Directory of Open Access Journals (Sweden)

    Jun Ren

    2014-01-01

    Full Text Available Many evidences have demonstrated that protein complexes are overlapping and hierarchically organized in PPI networks. Meanwhile, the large size of PPI network wants complex detection methods have low time complexity. Up to now, few methods can identify overlapping and hierarchical protein complexes in a PPI network quickly. In this paper, a novel method, called MCSE, is proposed based on λ-module and “seed-expanding.” First, it chooses seeds as essential PPIs or edges with high edge clustering values. Then, it identifies protein complexes by expanding each seed to a λ-module. MCSE is suitable for large PPI networks because of its low time complexity. MCSE can identify overlapping protein complexes naturally because a protein can be visited by different seeds. MCSE uses the parameter λ_th to control the range of seed expanding and can detect a hierarchical organization of protein complexes by tuning the value of λ_th. Experimental results of S. cerevisiae show that this hierarchical organization is similar to that of known complexes in MIPS database. The experimental results also show that MCSE outperforms other previous competing algorithms, such as CPM, CMC, Core-Attachment, Dpclus, HC-PIN, MCL, and NFC, in terms of the functional enrichment and matching with known protein complexes.

  5. Design methods for structures under thermal ratchet

    International Nuclear Information System (INIS)

    Branca, T.R.; McLean, J.L.

    1975-01-01

    Previous work on the thermal ratchet analysis of a simple pipe is extended to the case of an intersection of a pipe with a spherical shell. The chosen nozzle configuration is subjected to an internal pressure which remains constant, and a cyclic thermal transient which is representative of the type of transient that might be expected for components of a LMFBR. A number of cross-sections through the nozzle were examined, each yielding a different combination of elastic primary and secondary stress. These stresses, together with their associated cyclic strain growth, as determined from an elastic-plastic-creep analysis of the nozzle, were then plotted on a Miller or Bree-type diagram. Thus, a number of points, one for each cross-section considered, were available for comparison with the data obtained from the ratchet analysis of simple pipe sections. Both the elastic and inelastic analyses on the nozzle were performed using the finite element method of structural analysis of the ANSYS computer code. The pipe ratchetting cases were computed using the Oak Ridge National Laboratory PLACRE code. For a simple pipe ratchet case, a brief comparison is given between the version of ANSYS used in this study, the ANSYS version used in previous work and PLACRE code. The three programs did not yield identical results. Further study is needed to resolve the discrepancies that were observed. The results of the comparison between the nozzle ratchet and pipe ratchet solutions indicate that reasonable predictions can be made for the nozzle ratchet strains based on elastic parameters and design curves developed from pipe ratchetting solutions. (author)

  6. Trade-off between positive and negative design of protein stability: from lattice models to real proteins.

    Directory of Open Access Journals (Sweden)

    Orly Noivirt-Brik

    2009-12-01

    Full Text Available Two different strategies for stabilizing proteins are (i positive design in which the native state is stabilized and (ii negative design in which competing non-native conformations are destabilized. Here, the circumstances under which one strategy might be favored over the other are explored in the case of lattice models of proteins and then generalized and discussed with regard to real proteins. The balance between positive and negative design of proteins is found to be determined by their average "contact-frequency", a property that corresponds to the fraction of states in the conformational ensemble of the sequence in which a pair of residues is in contact. Lattice model proteins with a high average contact-frequency are found to use negative design more than model proteins with a low average contact-frequency. A mathematical derivation of this result indicates that it is general and likely to hold also for real proteins. Comparison of the results of correlated mutation analysis for real proteins with typical contact-frequencies to those of proteins likely to have high contact-frequencies (such as disordered proteins and proteins that are dependent on chaperonins for their folding indicates that the latter tend to have stronger interactions between residues that are not in contact in their native conformation. Hence, our work indicates that negative design is employed when insufficient stabilization is achieved via positive design owing to high contact-frequencies.

  7. Foundations of Digital Methods : Query Design

    NARCIS (Netherlands)

    Rogers, R.; Schäfer, M.T.; van Es, K.

    2017-01-01

    Broadly speaking digital methods may be considered the deployment of online tools and data for the purposes of social and medium research. More speci cally, they derive from online methods, or methods of the medium, which are reimagined and repurposed for research. The methods to be repurposed are

  8. Predicting Silk Fiber Mechanical Properties through Multiscale Simulation and Protein Design.

    Science.gov (United States)

    Rim, Nae-Gyune; Roberts, Erin G; Ebrahimi, Davoud; Dinjaski, Nina; Jacobsen, Matthew M; Martín-Moldes, Zaira; Buehler, Markus J; Kaplan, David L; Wong, Joyce Y

    2017-08-14

    Silk is a promising material for biomedical applications, and much research is focused on how application-specific, mechanical properties of silk can be designed synthetically through proper amino acid sequences and processing parameters. This protocol describes an iterative process between research disciplines that combines simulation, genetic synthesis, and fiber analysis to better design silk fibers with specific mechanical properties. Computational methods are used to assess the protein polymer structure as it forms an interconnected fiber network through shearing and how this process affects fiber mechanical properties. Model outcomes are validated experimentally with the genetic design of protein polymers that match the simulation structures, fiber fabrication from these polymers, and mechanical testing of these fibers. Through iterative feedback between computation, genetic synthesis, and fiber mechanical testing, this protocol will enable a priori prediction capability of recombinant material mechanical properties via insights from the resulting molecular architecture of the fiber network based entirely on the initial protein monomer composition. This style of protocol may be applied to other fields where a research team seeks to design a biomaterial with biomedical application-specific properties. This protocol highlights when and how the three research groups (simulation, synthesis, and engineering) should be interacting to arrive at the most effective method for predictive design of their material.

  9. Human Systems Interface Design Methods Using Ecological Interface Design Principles

    International Nuclear Information System (INIS)

    Hong, Seung Kweon; Park, Jung Chul; Kim, Sun Su; Sim, Kwang Pyo; Yuk, Seung Yul; Choi, Jae Hyeon; Yoon, Seung Hyun

    2009-12-01

    The results of this study categorized into two parts. The first part is the guidelines for EID designs. The procedure to observe for EID design is composed of 6 steps; 1) to define a target system, 2) to make an abstraction hierarchy model, 3) to check the link structure among each components included in the layers of abstraction hierarchy model, 4) to transform information requirements to variables, 5) to make the graphs related to each variables, 6) to check the graphs by visual display design principles and heuristic rules. The second part is an EID design alternative for nuclear power plant. The EID for high level function represents the energy balance and energy flow in each loop of nuclear power plant. The EID for middle level function represents the performance indicators of each equipment involved in the all processes of changing from coolants to steam. The EID for low level function represents the values measured in each equipment such as temperature, pressure, water level and so on

  10. Bionic Design Methods - A practical approach

    DEFF Research Database (Denmark)

    Kepler, Jørgen Asbøll; Stokholm, Marianne Denise J.

    2004-01-01

    Nature has served as inspiration for product design throughout history. Applications range from poetic translations of form to utilization of primary functional principles. This paper describes a generally applicable design methodology for transforming natural functional principles to feasible...... product design. From a formulation of design demands, which need not necessarily be very precise, the approach continues with a study of natural objects (anaimals, plants) which are subject to the same demands. From this study, the working principle(s) are derived. This (these) are then clarified through...... illustrative models, which should be simplified as much as possible. The simplified principle may now be evaluated and transformed into practical design. The methodology is clarified through examples, taken from a series of extended workshops held atAalborg University ....

  11. Protein-Based Nanoparticle Preparation via Nanoprecipitation Method

    Directory of Open Access Journals (Sweden)

    Mohamad Tarhini

    2018-03-01

    Full Text Available Nanoparticles are nowadays largely investigated in the field of drug delivery. Among nanoparticles, protein-based particles are of paramount importance since they are natural, biodegradable, biocompatible, and nontoxic. There are several methods to prepare proteins containing nanoparticles, but only a few studies have been dedicated to the preparation of protein- based nanoparticles. Then, the aim of this work was to report on the preparation of bovine serum albumin (BSA-based nanoparticles using a well-defined nanoprecipitation process. Special attention has been dedicated to a systematic study in order to understand separately the effect of each operating parameter of the method (such as protein concentration, solvent/non-solvent volume ratio, non-solvent injection rate, ionic strength of the buffer solution, pH, and cross-linking on the colloidal properties of the obtained nanoparticles. In addition, the mixing processes (batch or drop-wise were also investigated. Using a well-defined formulation, submicron protein-based nanoparticles have been obtained. All prepared particles have been characterized in terms of size, size distribution, morphology, and electrokinetic properties. In addition, the stability of nanoparticles was investigated using Ultraviolet (UV scan and electrophoresis, and the optimal conditions for preparing BSA nanoparticles by the nanoprecipitation method were concluded.

  12. Denatured state is critical in determining the properties of model proteins designed on different folds

    DEFF Research Database (Denmark)

    Amatori, Andrea; Ferkinghoff-Borg, Jesper; Tiana, Guido

    2008-01-01

    The thermodynamics of proteins designed on three common folds (SH3, chymotrypsin inhibitor 2 [CI2], and protein G) is studied with a simplified C alpha, model and compared with the thermodynamics of proteins designed on random-generated folds. The model allows to design sequences to fold within a...

  13. Hybrid Methods in Designing Sierpinski Gasket Antennas

    Directory of Open Access Journals (Sweden)

    Mudrik Alaydrus

    2010-12-01

    Full Text Available Sierpinki gasket antennas as example of fractal antennas show multiband characteristics. The computer simulation of Sierpinksi gasket monopole with finite ground needs prohibitively large computer memory and more computational time. Hybrid methods consist of surface integral equation method and physical optics or uniform geometrical theory of diffraction should alleviate this computational burdens. The so-called full hybridization of the different methods with modifying the incoming electromagnetic waves in case of hybrid method surface integral equation method and physical optics and modification of the Greens function for hybrid method surface integral equation method and uniform geometrical theory of diffraction plays the central role in the observation. Comparison between results of different methods are given and also measurements of three Sierpinksi gasket antennas. The multiband characteristics of the antennas still can be seen with some reduction and enhancement of resonances.

  14. Participatory design methods in telemedicine research

    DEFF Research Database (Denmark)

    Clemensen, Jane; Rothmann, Mette Juel; Smith, Anthony C.

    2017-01-01

    Healthcare systems require a paradigm shift in the way healthcare services are delivered to counteract demographic changes in patient populations, expanding technological developments and the increasing complexity of healthcare. Participatory design (PD) is a methodology that promotes the partici...

  15. Demystifying Mixed Methods Research Design: A Review of the Literature

    Science.gov (United States)

    Caruth, Gail D.

    2013-01-01

    Mixed methods research evolved in response to the observed limitations of both quantitative and qualitative designs and is a more complex method. The purpose of this paper was to examine mixed methods research in an attempt to demystify the design thereby allowing those less familiar with its design an opportunity to utilize it in future research.…

  16. Comparative methods of concrete portal frame design

    OpenAIRE

    A, Letengsang

    2014-01-01

    The objective of this thesis was to design a concrete portal frame with two column spacings of 12 meters and 6 meters and its structural elements in a building located in Hämeenlinna city, Finland. A comprehension study on the concrete design chapter of Eurocode 2 was done before proceeding on the calculation process, the materials’ properties. The corresponding ca-pacity diagrams from concrete product manufacturers in Finland can be assistance tools during the calculation process. ...

  17. A discussion of molecular biology methods for protein engineering

    CSIR Research Space (South Africa)

    Zawaira, A

    2011-09-01

    Full Text Available A number of molecular biology techniques are available to generate variants from a particular start gene for eventual protein expression. The authors discuss the basic principles of these methods in a repertoire that may be used to achieve...

  18. Methods of use of cellulose binding domain proteins

    Science.gov (United States)

    Shoseyov, Oded; Shpiegl, Itai; Goldstein, Marc A.; Doi, Roy H.

    1997-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  19. Toponomics method for the automated quantification of membrane protein translocation.

    Science.gov (United States)

    Domanova, Olga; Borbe, Stefan; Mühlfeld, Stefanie; Becker, Martin; Kubitz, Ralf; Häussinger, Dieter; Berlage, Thomas

    2011-09-19

    Intra-cellular and inter-cellular protein translocation can be observed by microscopic imaging of tissue sections prepared immunohistochemically. A manual densitometric analysis is time-consuming, subjective and error-prone. An automated quantification is faster, more reproducible, and should yield results comparable to manual evaluation. The automated method presented here was developed on rat liver tissue sections to study the translocation of bile salt transport proteins in hepatocytes. For validation, the cholestatic liver state was compared to the normal biological state. An automated quantification method was developed to analyze the translocation of membrane proteins and evaluated in comparison to an established manual method. Firstly, regions of interest (membrane fragments) are identified in confocal microscopy images. Further, densitometric intensity profiles are extracted orthogonally to membrane fragments, following the direction from the plasma membrane to cytoplasm. Finally, several different quantitative descriptors were derived from the densitometric profiles and were compared regarding their statistical significance with respect to the transport protein distribution. Stable performance, robustness and reproducibility were tested using several independent experimental datasets. A fully automated workflow for the information extraction and statistical evaluation has been developed and produces robust results. New descriptors for the intensity distribution profiles were found to be more discriminative, i.e. more significant, than those used in previous research publications for the translocation quantification. The slow manual calculation can be substituted by the fast and unbiased automated method.

  20. T-method duct design. Part 3

    International Nuclear Information System (INIS)

    Tsal, R.J.; Behls, H.F.; Mangel, R.

    1990-01-01

    This paper introduces a new method for simulating HVAC duct systems, called T-method. The desirability of simulation appears in many HVAC problems, such as determining system operating efficiency, system retrofitting, nuclear plant normal/emergency conditions, fire/smoke control systems, fans operating in parallel, pressure balancing after system modification, and noise generated by dampers. T-method is capable of simulating these problems. This paper includes problem definition, a theoretical approach, calculation procedures, and many examples

  1. Trends in the Design and Development of Specific Aptamers Against Peptides and Proteins.

    Science.gov (United States)

    Tabarzad, Maryam; Jafari, Marzieh

    2016-04-01

    Aptamers are single stranded oligonucleotides, comparable to monoclonal antibodies (mAbs) in selectivity and affinity and have significant strategic properties in design, development and applications more than mAbs. Ease of design and development, simple chemical modification and the attachment of functional groups, easily handling and more adaptability with analytical methods, small size and adaptation with nanostructures are the valuable characteristics of aptamers in comparison to large protein based ligands. Among a broad range of targets that their specific aptamers developed, proteins and peptides have significant position according to the number of related studies performed so far. Since proteins control many of important physiological and pathological incidents in the living organisms, particularly human beings and because of the benefits of aptamers in clinical and analytical applications, aptamer related technologies in the field of proteins and peptides are under progress, exclusively. Currently, there is only one FDA approved therapeutic aptamer in the pharmaceutical market, which is specific to vascular endothelial growth factor and is prescribed for age related macular degenerative disease. Additionally, there are several aptamers in the different phases of clinical trials. Almost all of these aptamers are specific to clinically important peptide or protein targets. In addition, the application of protein specific aptamers in the design and development of targeted drug delivery systems and diagnostic biosensors is another interesting field of aptamer technology. In this review, significant efforts related to development and applications of aptamer technologies in proteins and peptides sciences were considered to emphasis on the importance of aptamers in medicinal and clinical applications.

  2. Empirical pillar design methods review report: Final report

    International Nuclear Information System (INIS)

    1988-02-01

    This report summarizes and evaluates empirical pillar design methods that may be of use during the conceptual design of a high-level nuclear waste repository in salt. The methods are discussed according to category (i.e, main, submain, and panel pillars; barrier pillars; and shaft pillars). Of the 21 identified for main, submain, and panel pillars, one method, the Confined Core Method, is evaluated as being most appropriate for conceptual design. Five methods are considered potentially applicable. Of six methods identified for barrier pillars, one method based on the Load Transfer Distance concept is considered most appropriate for design. Based on the evaluation of 25 methods identified for shaft pillars, an approximate sizing criterion is proposed for use in conceptual design. Aspects of pillar performance relating to creep, ground deformation, interaction with roof and floor rock, and response to high temperature environments are not adequately addressed by existing empirical design methods. 152 refs., 22 figs., 14 tabs

  3. User interface inspection methods a user-centered design method

    CERN Document Server

    Wilson, Chauncey

    2014-01-01

    User Interface Inspection Methods succinctly covers five inspection methods: heuristic evaluation, perspective-based user interface inspection, cognitive walkthrough, pluralistic walkthrough, and formal usability inspections. Heuristic evaluation is perhaps the best-known inspection method, requiring a group of evaluators to review a product against a set of general principles. The perspective-based user interface inspection is based on the principle that different perspectives will find different problems in a user interface. In the related persona-based inspection, colleagues assume the

  4. A Simple Combinatorial Codon Mutagenesis Method for Targeted Protein Engineering.

    Science.gov (United States)

    Belsare, Ketaki D; Andorfer, Mary C; Cardenas, Frida S; Chael, Julia R; Park, Hyun June; Lewis, Jared C

    2017-03-17

    Directed evolution is a powerful tool for optimizing enzymes, and mutagenesis methods that improve enzyme library quality can significantly expedite the evolution process. Here, we report a simple method for targeted combinatorial codon mutagenesis (CCM). To demonstrate the utility of this method for protein engineering, CCM libraries were constructed for cytochrome P450 BM3 , pfu prolyl oligopeptidase, and the flavin-dependent halogenase RebH; 10-26 sites were targeted for codon mutagenesis in each of these enzymes, and libraries with a tunable average of 1-7 codon mutations per gene were generated. Each of these libraries provided improved enzymes for their respective transformations, which highlights the generality, simplicity, and tunability of CCM for targeted protein engineering.

  5. How to Construct a Mixed Methods Research Design

    OpenAIRE

    Schoonenboom, Judith; Johnson, R. Burke

    2017-01-01

    This article provides researchers with knowledge of how to design a high quality mixed methods research study. To design a mixed study, researchers must understand and carefully consider each of the dimensions of mixed methods design, and always keep an eye on the issue of validity. We explain the seven major design dimensions: purpose, theoretical drive, timing (simultaneity and dependency), point of integration, typological versus interactive design approaches, planned versus emergent desig...

  6. A dielectrophoresis-impedance method for protein detection and analysis

    Science.gov (United States)

    Mohamad, Ahmad Sabry; Hamzah, Roszymah; Hoettges, Kai F.; Hughes, Michael Pycraft

    2017-01-01

    Dielectrophoresis (DEP) has increasingly been used for the assessment of the electrical properties of molecular scale objects including proteins, DNA, nanotubes and nanowires. However, whilst techniques have been developed for the electrical characterisation of frequency-dependent DEP response, biomolecular study is usually limited to observation using fluorescent markers, limiting its applicability as a characterisation tool. In this paper we present a label-free, impedance-based method of characterisation applied to the determination of the electrical properties of colloidal protein molecules, specifically Bovine Serum Albumin (BSA). By monitoring the impedance between electrodes as proteins collect, it is shown to be possible to observe multi-dispersion behaviour. A DEP dispersion exhibited at 400 kHz is attributable to the orientational dispersion of the molecule, whilst a second, higher-frequency dispersion is attributed to a Maxwell-Wagner type dispersion; changes in behaviour with medium conductivity suggest that this is strongly influenced by the electrical double layer surrounding the molecule.

  7. Enhanced detection method for corneal protein identification using shotgun proteomics

    Directory of Open Access Journals (Sweden)

    Schlager John J

    2009-06-01

    Full Text Available Abstract Background The cornea is a specialized transparent connective tissue responsible for the majority of light refraction and image focus for the retina. There are three main layers of the cornea: the epithelium that is exposed and acts as a protective barrier for the eye, the center stroma consisting of parallel collagen fibrils that refract light, and the endothelium that is responsible for hydration of the cornea from the aqueous humor. Normal cornea is an immunologically privileged tissue devoid of blood vessels, but injury can produce a loss of these conditions causing invasion of other processes that degrade the homeostatic properties resulting in a decrease in the amount of light refracted onto the retina. Determining a measure and drift of phenotypic cornea state from normal to an injured or diseased state requires knowledge of the existing protein signature within the tissue. In the study of corneal proteins, proteomics procedures have typically involved the pulverization of the entire cornea prior to analysis. Separation of the epithelium and endothelium from the core stroma and performing separate shotgun proteomics using liquid chromatography/mass spectrometry results in identification of many more proteins than previously employed methods using complete pulverized cornea. Results Rabbit corneas were purchased, the epithelium and endothelium regions were removed, proteins processed and separately analyzed using liquid chromatography/mass spectrometry. Proteins identified from separate layers were compared against results from complete corneal samples. Protein digests were separated using a six hour liquid chromatographic gradient and ion-trap mass spectrometry used for detection of eluted peptide fractions. The SEQUEST database search results were filtered to allow only proteins with match probabilities of equal or better than 10-3 and peptides with a probability of 10-2 or less with at least two unique peptides isolated within

  8. The application of mixed methods designs to trauma research.

    Science.gov (United States)

    Creswell, John W; Zhang, Wanqing

    2009-12-01

    Despite the use of quantitative and qualitative data in trauma research and therapy, mixed methods studies in this field have not been analyzed to help researchers designing investigations. This discussion begins by reviewing four core characteristics of mixed methods research in the social and human sciences. Combining these characteristics, the authors focus on four select mixed methods designs that are applicable in trauma research. These designs are defined and their essential elements noted. Applying these designs to trauma research, a search was conducted to locate mixed methods trauma studies. From this search, one sample study was selected, and its characteristics of mixed methods procedures noted. Finally, drawing on other mixed methods designs available, several follow-up mixed methods studies were described for this sample study, enabling trauma researchers to view design options for applying mixed methods research in trauma investigations.

  9. Soft Computing Methods in Design of Superalloys

    Science.gov (United States)

    Cios, K. J.; Berke, L.; Vary, A.; Sharma, S.

    1996-01-01

    Soft computing techniques of neural networks and genetic algorithms are used in the design of superalloys. The cyclic oxidation attack parameter K(sub a), generated from tests at NASA Lewis Research Center, is modelled as a function of the superalloy chemistry and test temperature using a neural network. This model is then used in conjunction with a genetic algorithm to obtain an optimized superalloy composition resulting in low K(sub a) values.

  10. An ensemble method for predicting subnuclear localizations from primary protein structures.

    Directory of Open Access Journals (Sweden)

    Guo Sheng Han

    Full Text Available BACKGROUND: Predicting protein subnuclear localization is a challenging problem. Some previous works based on non-sequence information including Gene Ontology annotations and kernel fusion have respective limitations. The aim of this work is twofold: one is to propose a novel individual feature extraction method; another is to develop an ensemble method to improve prediction performance using comprehensive information represented in the form of high dimensional feature vector obtained by 11 feature extraction methods. METHODOLOGY/PRINCIPAL FINDINGS: A novel two-stage multiclass support vector machine is proposed to predict protein subnuclear localizations. It only considers those feature extraction methods based on amino acid classifications and physicochemical properties. In order to speed up our system, an automatic search method for the kernel parameter is used. The prediction performance of our method is evaluated on four datasets: Lei dataset, multi-localization dataset, SNL9 dataset and a new independent dataset. The overall accuracy of prediction for 6 localizations on Lei dataset is 75.2% and that for 9 localizations on SNL9 dataset is 72.1% in the leave-one-out cross validation, 71.7% for the multi-localization dataset and 69.8% for the new independent dataset, respectively. Comparisons with those existing methods show that our method performs better for both single-localization and multi-localization proteins and achieves more balanced sensitivities and specificities on large-size and small-size subcellular localizations. The overall accuracy improvements are 4.0% and 4.7% for single-localization proteins and 6.5% for multi-localization proteins. The reliability and stability of our classification model are further confirmed by permutation analysis. CONCLUSIONS: It can be concluded that our method is effective and valuable for predicting protein subnuclear localizations. A web server has been designed to implement the proposed method

  11. Oligomerization of G protein-coupled receptors: computational methods.

    Science.gov (United States)

    Selent, J; Kaczor, A A

    2011-01-01

    Recent research has unveiled the complexity of mechanisms involved in G protein-coupled receptor (GPCR) functioning in which receptor dimerization/oligomerization may play an important role. Although the first high-resolution X-ray structure for a likely functional chemokine receptor dimer has been deposited in the Protein Data Bank, the interactions and mechanisms of dimer formation are not yet fully understood. In this respect, computational methods play a key role for predicting accurate GPCR complexes. This review outlines computational approaches focusing on sequence- and structure-based methodologies as well as discusses their advantages and limitations. Sequence-based approaches that search for possible protein-protein interfaces in GPCR complexes have been applied with success in several studies, but did not yield always consistent results. Structure-based methodologies are a potent complement to sequence-based approaches. For instance, protein-protein docking is a valuable method especially when guided by experimental constraints. Some disadvantages like limited receptor flexibility and non-consideration of the membrane environment have to be taken into account. Molecular dynamics simulation can overcome these drawbacks giving a detailed description of conformational changes in a native-like membrane. Successful prediction of GPCR complexes using computational approaches combined with experimental efforts may help to understand the role of dimeric/oligomeric GPCR complexes for fine-tuning receptor signaling. Moreover, since such GPCR complexes have attracted interest as potential drug target for diverse diseases, unveiling molecular determinants of dimerization/oligomerization can provide important implications for drug discovery.

  12. Flexible Molybdenum Electrodes towards Designing Affinity Based Protein Biosensors.

    Science.gov (United States)

    Kamakoti, Vikramshankar; Panneer Selvam, Anjan; Radha Shanmugam, Nandhinee; Muthukumar, Sriram; Prasad, Shalini

    2016-07-18

    Molybdenum electrode based flexible biosensor on porous polyamide substrates has been fabricated and tested for its functionality as a protein affinity based biosensor. The biosensor performance was evaluated using a key cardiac biomarker; cardiac Troponin-I (cTnI). Molybdenum is a transition metal and demonstrates electrochemical behavior upon interaction with an electrolyte. We have leveraged this property of molybdenum for designing an affinity based biosensor using electrochemical impedance spectroscopy. We have evaluated the feasibility of detection of cTnI in phosphate-buffered saline (PBS) and human serum (HS) by measuring impedance changes over a frequency window from 100 mHz to 1 MHz. Increasing changes to the measured impedance was correlated to the increased dose of cTnI molecules binding to the cTnI antibody functionalized molybdenum surface. We achieved cTnI detection limit of 10 pg/mL in PBS and 1 ng/mL in HS medium. The use of flexible substrates for designing the biosensor demonstrates promise for integration with a large-scale batch manufacturing process.

  13. Demystifying Mixed Methods Research Design: A Review of the Literature

    OpenAIRE

    Gail D. Caruth

    2013-01-01

    Mixed methods research evolved in response to the observed limitations of both quantitative and qualitative designs and is a more complex method. The purpose of this paper was to examine mixed methods research in an attempt to demystify the design thereby allowing those less familiar with its design an opportunity to utilize it in future research. A review of the literature revealed that it has been gaining acceptance among researchers, researchers have begun using mixed methods research, it ...

  14. Bifurcation-free design method of pulse energy converter controllers

    International Nuclear Information System (INIS)

    Kolokolov, Yury; Ustinov, Pavel; Essounbouli, Najib; Hamzaoui, Abdelaziz

    2009-01-01

    In this paper, a design method of pulse energy converter (PEC) controllers is proposed. This method develops a classical frequency domain design, based on the small signal modeling, by means of an addition of a nonlinear dynamics analysis stage. The main idea of the proposed method consists in fact that the PEC controller, designed with an application of the small signal modeling, is tuned after with taking into the consideration an essentially nonlinear nature of the PEC that makes it possible to avoid bifurcation phenomena in the PEC dynamics at the design stage (bifurcation-free design). Also application of the proposed method allows an improvement of the designed controller performance. The application of this bifurcation-free design method is demonstrated on an example of the controller design of direct current-direct current (DC-DC) buck converter with an input electromagnetic interference filter.

  15. Comprehensive evaluation method in application of nuclear DCS product design

    International Nuclear Information System (INIS)

    Wang Weixin; Zhao Zhemin; Shi Yingbin

    2014-01-01

    In order to select the best design proposal in short time, the TOPSIS comprehensive evaluation method in the nuclear power plant DCS product design was introduced. It can intuitively show the different design proposals good or not good by data and shorten the time of the design proposal optimization. The design proposal selected by this method will be more reasonable and has good comprehensive performance indexes. The TOPSIS comprehensive evaluation method achieves good result in one of the nuclear power plant DCS cabinet design proposal optimization. (authors)

  16. Comparative characteristic of the methods of protein antigens epitope mapping

    Directory of Open Access Journals (Sweden)

    O. Yu. Galkin

    2014-08-01

    Full Text Available Comparative analysis of experimental methods of epitope mapping of protein antigens has been carried out. The vast majority of known techniques are involved in immunochemical study of the interaction of protein molecules or peptides with antibodies of corresponding specifici­ty. The most effective and widely applicable metho­dological techniques are those that use synthetic and genetically engineered peptides. Over the past 30 years, these groups of methods have travelled a notable evolutionary path up to the maximum automation and the detection of antigenic determinants of various types (linear and conformational epitopes, and mimotopes. Most of epitope searching algorithms were integrated into a computer program, which greatly facilitates the analysis of experimental data and makes it possible to create spatial models. It is possible to use comparative epitope mapping for solving the applied problems; this less time-consuming method is based on the analysis of competition between different antibodies interactions with the same antigen. The physical method of antigenic structure study is X-ray analysis of antigen-antibody complexes, which may be applied only to crystallizing­ proteins, and nuclear magnetic resonance.

  17. Software Design Methods for Real-Time Systems

    Science.gov (United States)

    1989-12-01

    This module describes the concepts and methods used in the software design of real time systems . It outlines the characteristics of real time systems , describes...the role of software design in real time system development, surveys and compares some software design methods for real - time systems , and

  18. Design methods for high temperature power plant structures

    International Nuclear Information System (INIS)

    Townley, C.H.A.

    1984-01-01

    The subject is discussed under the headings: introduction (scope of paper - reviews of design methods and design criteria currently in use for both nuclear and fossil fuelled power plant; examples chosen are (a) BS 1113, representative of design codes employed for power station boiler plant; (b) ASME Code Case N47, which is being developed for high temperature nuclear reactors, especially the liquid metal fast breeder reactor); design codes for power station boilers; Code Case N47 (design in the absence of thermal shock and thermal fatigue; design against cyclic loading at high temperature; further research in support of high temperature design methods and criteria for LMFBRs); concluding remarks. (U.K.)

  19. The Triton: Design concepts and methods

    Science.gov (United States)

    Meholic, Greg; Singer, Michael; Vanryn, Percy; Brown, Rhonda; Tella, Gustavo; Harvey, Bob

    1992-01-01

    During the design of the C & P Aerospace Triton, a few problems were encountered that necessitated changes in the configuration. After the initial concept phase, the aspect ratio was increased from 7 to 7.6 to produce a greater lift to drag ratio (L/D = 13) which satisfied the horsepower requirements (118 hp using the Lycoming O-235 engine). The initial concept had a wing planform area of 134 sq. ft. Detailed wing sizing analysis enlarged the planform area to 150 sq. ft., without changing its layout or location. The most significant changes, however, were made just prior to inboard profile design. The fuselage external diameter was reduced from 54 to 50 inches to reduce drag to meet the desired cruise speed of 120 knots. Also, the nose was extended 6 inches to accommodate landing gear placement. Without the extension, the nosewheel received an unacceptable percentage (25 percent) of the landing weight. The final change in the configuration was made in accordance with the stability and control analysis. In order to reduce the static margin from 20 to 13 percent, the horizontal tail area was reduced from 32.02 to 25.0 sq. ft. The Triton meets all the specifications set forth in the design criteria. If time permitted another iteration of the calculations, two significant changes would be made. The vertical stabilizer area would be reduced to decrease the aircraft lateral stability slope since the current value was too high in relation to the directional stability slope. Also, the aileron size would be decreased to reduce the roll rate below the current 106 deg/second. Doing so would allow greater flap area (increasing CL(sub max)) and thus reduce the overall wing area. C & P would also recalculate the horsepower and drag values to further validate the 120 knot cruising speed.

  20. Protein-protein interactions as a strategy towards protein-specific drug design: the example of ataxin-1.

    Directory of Open Access Journals (Sweden)

    Cesira de Chiara

    Full Text Available A main challenge for structural biologists is to understand the mechanisms that discriminate between molecular interactions and determine function. Here, we show how partner recognition of the AXH domain of the transcriptional co-regulator ataxin-1 is fine-tuned by a subtle balance between self- and hetero-associations. Ataxin-1 is the protein responsible for the hereditary spinocerebellar ataxia type 1, a disease linked to protein aggregation and transcriptional dysregulation. Expansion of a polyglutamine tract is essential for ataxin-1 aggregation, but the sequence-wise distant AXH domain plays an important aggravating role in the process. The AXH domain is also a key element for non-aberrant function as it intervenes in interactions with multiple protein partners. Previous data have shown that AXH is dimeric in solution and forms a dimer of dimers when crystallized. By solving the structure of a complex of AXH with a peptide from the interacting transcriptional repressor CIC, we show that the dimer interface of AXH is displaced by the new interaction and that, when blocked by the CIC peptide AXH aggregation and misfolding are impaired. This is a unique example in which palindromic self- and hetero-interactions within a sequence with chameleon properties discriminate the partner. We propose a drug design strategy for the treatment of SCA1 that is based on the information gained from the AXH/CIC complex.

  1. Collaborative Design Method Holistic Participation (MHP)

    NARCIS (Netherlands)

    Proveniers, A.G.W.J.; Schmid, P.; Schmid-Pa'l, G.; Klucznik-Toro, A.; Csepe, A.; Kwiatkowska-Ciotucha, D.

    2009-01-01

    Almost by definition, innovative, sustainable, peaceful economics, technologies, derived services and products have to be developed in an interdisciplinary way: all kinds of bits and parts from less sustainable methods, technologies, services and products have to be reshuffled in new innovative,

  2. Searching for the Pareto frontier in multi-objective protein design.

    Science.gov (United States)

    Nanda, Vikas; Belure, Sandeep V; Shir, Ofer M

    2017-08-01

    The goal of protein engineering and design is to identify sequences that adopt three-dimensional structures of desired function. Often, this is treated as a single-objective optimization problem, identifying the sequence-structure solution with the lowest computed free energy of folding. However, many design problems are multi-state, multi-specificity, or otherwise require concurrent optimization of multiple objectives. There may be tradeoffs among objectives, where improving one feature requires compromising another. The challenge lies in determining solutions that are part of the Pareto optimal set-designs where no further improvement can be achieved in any of the objectives without degrading one of the others. Pareto optimality problems are found in all areas of study, from economics to engineering to biology, and computational methods have been developed specifically to identify the Pareto frontier. We review progress in multi-objective protein design, the development of Pareto optimization methods, and present a specific case study using multi-objective optimization methods to model the tradeoff between three parameters, stability, specificity, and complexity, of a set of interacting synthetic collagen peptides.

  3. Molecular design and nanoparticle-mediated intracellular delivery of functional proteins to target cellular pathways

    Science.gov (United States)

    Shah, Dhiral Ashwin

    Intracellular delivery of specific proteins and peptides represents a novel method to influence stem cells for gain-of-function and loss-of-function. Signaling control is vital in stem cells, wherein intricate control of and interplay among critical pathways directs the fate of these cells into either self-renewal or differentiation. The most common route to manipulate cellular function involves the introduction of genetic material such as full-length genes and shRNA into the cell to generate (or prevent formation of) the target protein, and thereby ultimately alter cell function. However, viral-mediated gene delivery may result in relatively slow expression of proteins and prevalence of oncogene insertion into the cell, which can alter cell function in an unpredictable fashion, and non-viral delivery may lead to low efficiency of genetic delivery. For example, the latter case plagues the generation of induced pluripotent stem cells (iPSCs) and hinders their use for in vivo applications. Alternatively, introducing proteins into cells that specifically recognize and influence target proteins, can result in immediate deactivation or activation of key signaling pathways within the cell. In this work, we demonstrate the cellular delivery of functional proteins attached to hydrophobically modified silica (SiNP) nanoparticles to manipulate specifically targeted cell signaling proteins. In the Wnt signaling pathway, we have targeted the phosphorylation activity of glycogen synthase kinase-3beta (GSK-3beta) by designing a chimeric protein and delivering it in neural stem cells. Confocal imaging indicates that the SiNP-chimeric protein conjugates were efficiently delivered to the cytosol of human embryonic kidney cells and rat neural stem cells, presumably via endocytosis. This uptake impacted the Wnt signaling cascade, indicated by the elevation of beta-catenin levels, and increased transcription of Wnt target genes, such as c-MYC. The results presented here suggest that

  4. Protein consensus-based surface engineering (ProCoS): a computer-assisted method for directed protein evolution.

    Science.gov (United States)

    Shivange, Amol V; Hoeffken, Hans Wolfgang; Haefner, Stefan; Schwaneberg, Ulrich

    2016-12-01

    Protein consensus-based surface engineering (ProCoS) is a simple and efficient method for directed protein evolution combining computational analysis and molecular biology tools to engineer protein surfaces. ProCoS is based on the hypothesis that conserved residues originated from a common ancestor and that these residues are crucial for the function of a protein, whereas highly variable regions (situated on the surface of a protein) can be targeted for surface engineering to maximize performance. ProCoS comprises four main steps: ( i ) identification of conserved and highly variable regions; ( ii ) protein sequence design by substituting residues in the highly variable regions, and gene synthesis; ( iii ) in vitro DNA recombination of synthetic genes; and ( iv ) screening for active variants. ProCoS is a simple method for surface mutagenesis in which multiple sequence alignment is used for selection of surface residues based on a structural model. To demonstrate the technique's utility for directed evolution, the surface of a phytase enzyme from Yersinia mollaretii (Ymphytase) was subjected to ProCoS. Screening just 1050 clones from ProCoS engineering-guided mutant libraries yielded an enzyme with 34 amino acid substitutions. The surface-engineered Ymphytase exhibited 3.8-fold higher pH stability (at pH 2.8 for 3 h) and retained 40% of the enzyme's specific activity (400 U/mg) compared with the wild-type Ymphytase. The pH stability might be attributed to a significantly increased (20 percentage points; from 9% to 29%) number of negatively charged amino acids on the surface of the engineered phytase.

  5. De novo design and engineering of functional metal and porphyrin-binding protein domains

    Science.gov (United States)

    Everson, Bernard H.

    In this work, I describe an approach to the rational, iterative design and characterization of two functional cofactor-binding protein domains. First, a hybrid computational/experimental method was developed with the aim of algorithmically generating a suite of porphyrin-binding protein sequences with minimal mutual sequence information. This method was explored by generating libraries of sequences, which were then expressed and evaluated for function. One successful sequence is shown to bind a variety of porphyrin-like cofactors, and exhibits light- activated electron transfer in mixed hemin:chlorin e6 and hemin:Zn(II)-protoporphyrin IX complexes. These results imply that many sophisticated functions such as cofactor binding and electron transfer require only a very small number of residue positions in a protein sequence to be fixed. Net charge and hydrophobic content are important in determining protein solubility and stability. Accordingly, rational modifications were made to the aforementioned design procedure in order to improve its overall success rate. The effects of these modifications are explored using two `next-generation' sequence libraries, which were separately expressed and evaluated. Particular modifications to these design parameters are demonstrated to effectively double the purification success rate of the procedure. Finally, I describe the redesign of the artificial di-iron protein DF2 into CDM13, a single chain di-Manganese four-helix bundle. CDM13 acts as a functional model of natural manganese catalase, exhibiting a kcat of 0.08s-1 under steady-state conditions. The bound manganese cofactors have a reduction potential of +805 mV vs NHE, which is too high for efficient dismutation of hydrogen peroxide. These results indicate that as a high-potential manganese complex, CDM13 may represent a promising first step toward a polypeptide model of the Oxygen Evolving Complex of the photosynthetic enzyme Photosystem II.

  6. Seismic design method of free standing rack

    International Nuclear Information System (INIS)

    Taniguchi, Katsuhiko; Okuno, Daisaku; Iwasaki, Akihisa; Nekomoto, Yoshitsugu; Matsuoka, Toshihiro

    2013-01-01

    For high earthquake resistance and ease of installation, free standing racks which are not anchored to the pool floor or walls has been adopted in many countries. Under the earthquake, the response of the free standing rack is highly nonlinear and involves a complex combination of motions (sliding, rocking, twisting, and turning) and impacts between the fuel assemblies and the fuel cell walls, rack-to-rack, and the pit floor and rack pedestals. We carried out seismic experiments on the full-scale rack model in water and dry conditions to obtain the fundamental data about free standing rack (sliding, rocking and turning motions). We have developed the nonlinear dynamic analysis method to predict seismic response for the free standing rack utilizing the full-scale test result and verified the analysis evaluation method of the rack by comparison of test result. (author)

  7. 78 FR 67360 - Ambient Air Monitoring Reference and Equivalent Methods: Designation of Five New Equivalent Methods

    Science.gov (United States)

    2013-11-12

    ... Methods: Designation of Five New Equivalent Methods AGENCY: Office of Research and Development; Environmental Protection Agency (EPA). ACTION: Notice of the designation of five new equivalent methods for...) has designated, in accordance with 40 CFR Part 53, five new equivalent methods, one for measuring...

  8. Mass Spectrometry Coupled Experiments and Protein Structure Modeling Methods

    Directory of Open Access Journals (Sweden)

    Lee Sael

    2013-10-01

    Full Text Available With the accumulation of next generation sequencing data, there is increasing interest in the study of intra-species difference in molecular biology, especially in relation to disease analysis. Furthermore, the dynamics of the protein is being identified as a critical factor in its function. Although accuracy of protein structure prediction methods is high, provided there are structural templates, most methods are still insensitive to amino-acid differences at critical points that may change the overall structure. Also, predicted structures are inherently static and do not provide information about structural change over time. It is challenging to address the sensitivity and the dynamics by computational structure predictions alone. However, with the fast development of diverse mass spectrometry coupled experiments, low-resolution but fast and sensitive structural information can be obtained. This information can then be integrated into the structure prediction process to further improve the sensitivity and address the dynamics of the protein structures. For this purpose, this article focuses on reviewing two aspects: the types of mass spectrometry coupled experiments and structural data that are obtainable through those experiments; and the structure prediction methods that can utilize these data as constraints. Also, short review of current efforts in integrating experimental data in the structural modeling is provided.

  9. Distributed optimization for systems design : an augmented Lagrangian coordination method

    NARCIS (Netherlands)

    Tosserams, S.

    2008-01-01

    This thesis presents a coordination method for the distributed design optimization of engineering systems. The design of advanced engineering systems such as aircrafts, automated distribution centers, and microelectromechanical systems (MEMS) involves multiple components that together realize the

  10. Evaluation of Information Requirements of Reliability Methods in Engineering Design

    DEFF Research Database (Denmark)

    Marini, Vinicius Kaster; Restrepo-Giraldo, John Dairo; Ahmed-Kristensen, Saeema

    2010-01-01

    This paper aims to characterize the information needed to perform methods for robustness and reliability, and verify their applicability to early design stages. Several methods were evaluated on their support to synthesis in engineering design. Of those methods, FMEA, FTA and HAZOP were selected...

  11. A Review of Design Optimization Methods for Electrical Machines

    Directory of Open Access Journals (Sweden)

    Gang Lei

    2017-11-01

    Full Text Available Electrical machines are the hearts of many appliances, industrial equipment and systems. In the context of global sustainability, they must fulfill various requirements, not only physically and technologically but also environmentally. Therefore, their design optimization process becomes more and more complex as more engineering disciplines/domains and constraints are involved, such as electromagnetics, structural mechanics and heat transfer. This paper aims to present a review of the design optimization methods for electrical machines, including design analysis methods and models, optimization models, algorithms and methods/strategies. Several efficient optimization methods/strategies are highlighted with comments, including surrogate-model based and multi-level optimization methods. In addition, two promising and challenging topics in both academic and industrial communities are discussed, and two novel optimization methods are introduced for advanced design optimization of electrical machines. First, a system-level design optimization method is introduced for the development of advanced electric drive systems. Second, a robust design optimization method based on the design for six-sigma technique is introduced for high-quality manufacturing of electrical machines in production. Meanwhile, a proposal is presented for the development of a robust design optimization service based on industrial big data and cloud computing services. Finally, five future directions are proposed, including smart design optimization method for future intelligent design and production of electrical machines.

  12. A Systematic Optimization Design Method for Complex Mechatronic Products Design and Development

    Directory of Open Access Journals (Sweden)

    Jie Jiang

    2018-01-01

    Full Text Available Designing a complex mechatronic product involves multiple design variables, objectives, constraints, and evaluation criteria as well as their nonlinearly coupled relationships. The design space can be very big consisting of many functional design parameters, structural design parameters, and behavioral design (or running performances parameters. Given a big design space and inexplicit relations among them, how to design a product optimally in an optimization design process is a challenging research problem. In this paper, we propose a systematic optimization design method based on design space reduction and surrogate modelling techniques. This method firstly identifies key design parameters from a very big design space to reduce the design space, secondly uses the identified key design parameters to establish a system surrogate model based on data-driven modelling principles for optimization design, and thirdly utilizes the multiobjective optimization techniques to achieve an optimal design of a product in the reduced design space. This method has been tested with a high-speed train design. With comparison to others, the research results show that this method is practical and useful for optimally designing complex mechatronic products.

  13. Analytical techniques for instrument design - matrix methods

    International Nuclear Information System (INIS)

    Robinson, R.A.

    1997-01-01

    We take the traditional Cooper-Nathans approach, as has been applied for many years for steady-state triple-axis spectrometers, and consider its generalisation to other inelastic scattering spectrometers. This involves a number of simple manipulations of exponentials of quadratic forms. In particular, we discuss a toolbox of matrix manipulations that can be performed on the 6- dimensional Cooper-Nathans matrix: diagonalisation (Moller-Nielsen method), coordinate changes e.g. from (Δk I ,Δk F to ΔE, ΔQ ampersand 2 dummy variables), integration of one or more variables (e.g. over such dummy variables), integration subject to linear constraints (e.g. Bragg's Law for analysers), inversion to give the variance-covariance matrix, and so on. We show how these tools can be combined to solve a number of important problems, within the narrow-band limit and the gaussian approximation. We will argue that a generalised program that can handle multiple different spectrometers could (and should) be written in parallel to the Monte-Carlo packages that are becoming available. We will also discuss the complementarity between detailed Monte-Carlo calculations and the approach presented here. In particular, Monte-Carlo methods traditionally simulate the real experiment as performed in practice, given a model scattering law, while the Cooper-Nathans method asks the inverse question: given that a neutron turns up in a particular spectrometer configuration (e.g. angle and time of flight), what is the probability distribution of possible scattering events at the sample? The Monte-Carlo approach could be applied in the same spirit to this question

  14. Mixed Methods Designs for Sports Medicine Research.

    Science.gov (United States)

    Kay, Melissa C; Kucera, Kristen L

    2018-07-01

    Mixed methods research is a relatively new approach in the field of sports medicine, where the benefits of qualitative and quantitative research are combined while offsetting the other's flaws. Despite its known and successful use in other populations, it has been used minimally in sports medicine, including studies of the clinician perspective, concussion, and patient outcomes. Therefore, there is a need for this approach to be applied in other topic areas not easily addressed by one type of research approach in isolation, such as the retirement from sport, effects of and return from injury, and catastrophic injury. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Fluctuation Flooding Method (FFM) for accelerating conformational transitions of proteins

    Science.gov (United States)

    Harada, Ryuhei; Takano, Yu; Shigeta, Yasuteru

    2014-03-01

    A powerful conformational sampling method for accelerating structural transitions of proteins, "Fluctuation Flooding Method (FFM)," is proposed. In FFM, cycles of the following steps enhance the transitions: (i) extractions of largely fluctuating snapshots along anisotropic modes obtained from trajectories of multiple independent molecular dynamics (MD) simulations and (ii) conformational re-sampling of the snapshots via re-generations of initial velocities when re-starting MD simulations. In an application to bacteriophage T4 lysozyme, FFM successfully accelerated the open-closed transition with the 6 ns simulation starting solely from the open state, although the 1-μs canonical MD simulation failed to sample such a rare event.

  16. Analytical techniques for instrument design - Matrix methods

    International Nuclear Information System (INIS)

    Robinson, R.A.

    1997-01-01

    The authors take the traditional Cooper-Nathans approach, as has been applied for many years for steady-state triple-axis spectrometers, and consider its generalization to other inelastic scattering spectrometers. This involves a number of simple manipulations of exponentials of quadratic forms. In particular, they discuss a toolbox of matrix manipulations that can be performed on the 6-dimensional Cooper-Nathans matrix. They show how these tools can be combined to solve a number of important problems, within the narrow-band limit and the gaussian approximation. They will argue that a generalized program that can handle multiple different spectrometers could (and should) be written in parallel to the Monte-Carlo packages that are becoming available. They also discuss the complementarity between detailed Monte-Carlo calculations and the approach presented here. In particular, Monte-Carlo methods traditionally simulate the real experiment as performed in practice, given a model scattering law, while the Cooper-Nathans method asks the inverse question: given that a neutron turns up in a particular spectrometer configuration (e.g. angle and time of flight), what is the probability distribution of possible scattering events at the sample? The Monte-Carlo approach could be applied in the same spirit to this question

  17. Methods for the preparation of protein-oligonucleotide-lipid constructs.

    Science.gov (United States)

    Takasaki, Jennifer; Raney, Sameersingh G; Chikh, Ghania; Sekirov, Laura; Brodsky, Irina; Tam, Ying; Ansell, Steven M

    2006-01-01

    A mixture of ionizable cationic lipids, steric barrier lipids, and colipids is used to encapsulate oligonucleotide DNA in lipidic particles called SALP. This material is under development as an adjuvant for vaccines. Previously we have shown that coupling the antigen directly to the surface of SALP can lead to enhanced immunological responses in vivo. Two different methods for preparing ovalbumin-SALP were assessed in this work. Originally the conjugates were prepared by treating SALP containing a maleimide-derivatized lipid with thiolated ovalbumin, a method we refer to as active coupling. This reaction was found to be difficult to control and generally resulted in low coupling efficiencies. The issues relating to this approach were characterized. We have recently developed alternative techniques based on first coupling ovalbumin to a micelle and then incubating the resultant product with SALP, methods we refer to as passive coupling. We have shown that this method allows accurate control of the levels of protein associated SALP and does not suffer from surface saturation effects seen with the active coupling method that places maximum limits on the amount of protein that can be coupled to the SALP surface. The products from the passive coupling protocol are shown to have activity comparable to those derived from the active coupling protocol in investigations of in vivo immune responses.

  18. Methods for very high temperature design

    International Nuclear Information System (INIS)

    Blass, J.J.; Corum, J.M.; Chang, S.J.

    1989-01-01

    Design rules and procedures for high-temperature, gas-cooled reactor components are being formulated as an ASME Boiler and Pressure Vessel Code Case. A draft of the Case, patterned after Code Case N-47, and limited to Inconel 617 and temperatures of 982/degree/C (1800/degree/F) or less, will be completed in 1989 for consideration by relevant Code committees. The purpose of this paper is to provide a synopsis of the significant differences between the draft Case and N-47, and to provide more complete accounts of the development of allowable stress and stress rupture values and the development of isochronous stress vs strain curves, in both of which Oak Ridge National Laboratory (ORNL) played a principal role. The isochronous curves, which represent average behavior for many heats of Inconel 617, were based in part on a unified constitutive model developed at ORNL. Details are also provided of this model of inelastic deformation behavior, which does not distinguish between rate-dependent plasticity and time-dependent creep, along with comparisons between calculated and observed results of tests conducted on a typical heat of Inconel 617 by the General Electric Company for the Department of Energy. 4 refs., 15 figs., 1 tab

  19. Instrument design optimization with computational methods

    Energy Technology Data Exchange (ETDEWEB)

    Moore, Michael H. [Old Dominion Univ., Norfolk, VA (United States)

    2017-08-01

    Using Finite Element Analysis to approximate the solution of differential equations, two different instruments in experimental Hall C at the Thomas Jefferson National Accelerator Facility are analyzed. The time dependence of density uctuations from the liquid hydrogen (LH2) target used in the Qweak experiment (2011-2012) are studied with Computational Fluid Dynamics (CFD) and the simulation results compared to data from the experiment. The 2.5 kW liquid hydrogen target was the highest power LH2 target in the world and the first to be designed with CFD at Jefferson Lab. The first complete magnetic field simulation of the Super High Momentum Spectrometer (SHMS) is presented with a focus on primary electron beam deflection downstream of the target. The SHMS consists of a superconducting horizontal bending magnet (HB) and three superconducting quadrupole magnets. The HB allows particles scattered at an angle of 5:5 deg to the beam line to be steered into the quadrupole magnets which make up the optics of the spectrometer. Without mitigation, remnant fields from the SHMS may steer the unscattered beam outside of the acceptable envelope on the beam dump and limit beam operations at small scattering angles. A solution is proposed using optimal placement of a minimal amount of shielding iron around the beam line.

  20. A flexible layout design method for passive micromixers.

    Science.gov (United States)

    Deng, Yongbo; Liu, Zhenyu; Zhang, Ping; Liu, Yongshun; Gao, Qingyong; Wu, Yihui

    2012-10-01

    This paper discusses a flexible layout design method of passive micromixers based on the topology optimization of fluidic flows. Being different from the trial and error method, this method obtains the detailed layout of a passive micromixer according to the desired mixing performance by solving a topology optimization problem. Therefore, the dependence on the experience of the designer is weaken, when this method is used to design a passive micromixer with acceptable mixing performance. Several design disciplines for the passive micromixers are considered to demonstrate the flexibility of the layout design method for passive micromixers. These design disciplines include the approximation of the real 3D micromixer, the manufacturing feasibility, the spacial periodic design, and effects of the Péclet number and Reynolds number on the designs obtained by this layout design method. The capability of this design method is validated by several comparisons performed between the obtained layouts and the optimized designs in the recently published literatures, where the values of the mixing measurement is improved up to 40.4% for one cycle of the micromixer.

  1. How to Construct a Mixed Methods Research Design.

    Science.gov (United States)

    Schoonenboom, Judith; Johnson, R Burke

    2017-01-01

    This article provides researchers with knowledge of how to design a high quality mixed methods research study. To design a mixed study, researchers must understand and carefully consider each of the dimensions of mixed methods design, and always keep an eye on the issue of validity. We explain the seven major design dimensions: purpose, theoretical drive, timing (simultaneity and dependency), point of integration, typological versus interactive design approaches, planned versus emergent design, and design complexity. There also are multiple secondary dimensions that need to be considered during the design process. We explain ten secondary dimensions of design to be considered for each research study. We also provide two case studies showing how the mixed designs were constructed.

  2. The synthesis method for design of electron flow sources

    Science.gov (United States)

    Alexahin, Yu I.; Molodozhenzev, A. Yu

    1997-01-01

    The synthesis method to design a relativistic magnetically - focused beam source is described in this paper. It allows to find a shape of electrodes necessary to produce laminar space charge flows. Electron guns with shielded cathodes designed with this method were analyzed using the EGUN code. The obtained results have shown the coincidence of the synthesis and analysis calculations [1]. This method of electron gun calculation may be applied for immersed electron flows - of interest for the EBIS electron gun design.

  3. Design of compound libraries based on natural product scaffolds and protein structure similarity clustering (PSSC)

    NARCIS (Netherlands)

    Balamurugan, Rengarajan; Dekker, Frank J; Waldmann, Herbert; Dekker, Frans

    Recent advances in structural biology, bioinformatics and combinatorial chemistry have significantly impacted the discovery of small molecules that modulate protein functions. Natural products which have evolved to bind to proteins may serve as biologically validated starting points for the design

  4. STUDIES OF METHOD FOR DETERMINING THE PROTEIN CONCENTRATION OF "MALEIN PPD" BY THE KJELDAHL METHOD

    Directory of Open Access Journals (Sweden)

    Ciuca, V

    2017-06-01

    Full Text Available Glanders is a contagious and fatal disease of horses, donkeys, and mules, caused by infection with the bacterium Burkholderia mallei. The pathogen causes nodules and ulcerations in the upper respiratory tract and lungs. Glanders is transmissible to humans by direct contact with diseased animals or with infected or contaminated material. In the untreated acute disease, the mortality rate can reach 95% within 3 weeks Malein PPD - the diagnostic product contain max 2mg/ml Burkholderia mallei. The amount of protein in the biological product "Malein PPD" is measured as nitrogen from protein molecule, applying the Kjeldahl (method determination of nitrogen by sulphuric acid digestion. The validation study aims to demonstrate the determination of the protein of the Malein PPD, by sulphuric acid digestion, it is an appropriate analytical method, reproducible and meets the quality requirements of diagnostic reagents. The paper establishes the performance characteristics of the method considered and identify the factors that influence these characteristics. The method for determining the concentration of protein, by the Kjeldahl method is considered valid if the results obtained for each validation parameter are within the admissibility criteria.The validation procedure includes details on protocol working to determine the protein of the Malein PPD, validation criteria, experimental results, mathematical calculations.

  5. Comparison of Traditional Design Nonlinear Programming Optimization and Stochastic Methods for Structural Design

    Science.gov (United States)

    Patnaik, Surya N.; Pai, Shantaram S.; Coroneos, Rula M.

    2010-01-01

    Structural design generated by traditional method, optimization method and the stochastic design concept are compared. In the traditional method, the constraints are manipulated to obtain the design and weight is back calculated. In design optimization, the weight of a structure becomes the merit function with constraints imposed on failure modes and an optimization algorithm is used to generate the solution. Stochastic design concept accounts for uncertainties in loads, material properties, and other parameters and solution is obtained by solving a design optimization problem for a specified reliability. Acceptable solutions were produced by all the three methods. The variation in the weight calculated by the methods was modest. Some variation was noticed in designs calculated by the methods. The variation may be attributed to structural indeterminacy. It is prudent to develop design by all three methods prior to its fabrication. The traditional design method can be improved when the simplified sensitivities of the behavior constraint is used. Such sensitivity can reduce design calculations and may have a potential to unify the traditional and optimization methods. Weight versus reliabilitytraced out an inverted-S-shaped graph. The center of the graph corresponded to mean valued design. A heavy design with weight approaching infinity could be produced for a near-zero rate of failure. Weight can be reduced to a small value for a most failure-prone design. Probabilistic modeling of load and material properties remained a challenge.

  6. Relationships between the generalized functional method and other methods of nonimaging optical design.

    Science.gov (United States)

    Bortz, John; Shatz, Narkis

    2011-04-01

    The recently developed generalized functional method provides a means of designing nonimaging concentrators and luminaires for use with extended sources and receivers. We explore the mathematical relationships between optical designs produced using the generalized functional method and edge-ray, aplanatic, and simultaneous multiple surface (SMS) designs. Edge-ray and dual-surface aplanatic designs are shown to be special cases of generalized functional designs. In addition, it is shown that dual-surface SMS designs are closely related to generalized functional designs and that certain computational advantages accrue when the two design methods are combined. A number of examples are provided. © 2011 Optical Society of America

  7. PPI-IRO: A two-stage method for protein-protein interaction extraction based on interaction relation ontology

    KAUST Repository

    Li, Chuanxi; Chen, Peng; Wang, Rujing; Wang, Xiujie; Su, Yaru; Li, Jinyan

    2014-01-01

    Mining Protein-Protein Interactions (PPIs) from the fast-growing biomedical literature resources has been proven as an effective approach for the identifi cation of biological regulatory networks. This paper presents a novel method based on the idea

  8. Methodical Design of Software Architecture Using an Architecture Design Assistant (ArchE)

    Science.gov (United States)

    2005-04-01

    PA 15213-3890 Methodical Design of Software Architecture Using an Architecture Design Assistant (ArchE) Felix Bachmann and Mark Klein Software...DATES COVERED 00-00-2005 to 00-00-2005 4. TITLE AND SUBTITLE Methodical Design of Software Architecture Using an Architecture Design Assistant...important for architecture design – quality requirements and constraints are most important Here’s some evidence: If the only concern is

  9. Protein corona: a new approach for nanomedicine design

    Directory of Open Access Journals (Sweden)

    Nguyen VH

    2017-04-01

    Full Text Available Van Hong Nguyen, Beom-Jin Lee Department of Pharmacy, Bioavailability Control Laboratory, College of Pharmacy, Ajou University, Suwon, Republic of Korea Abstract: After administration of nanoparticle (NP into biological fluids, an NP–protein complex is formed, which represents the “true identity” of NP in our body. Hence, protein–NP interaction should be carefully investigated to predict and control the fate of NPs or drug-loaded NPs, including systemic circulation, biodistribution, and bioavailability. In this review, we mainly focus on the formation of protein corona and its potential applications in pharmaceutical sciences such as prediction modeling based on NP-adsorbed proteins, usage of active proteins for modifying NP to achieve toxicity reduction, circulation time enhancement, and targeting effect. Validated correlative models for NP biological responses mainly based on protein corona fingerprints of NPs are more highly accurate than the models solely set up from NP properties. Based on these models, effectiveness as well as the toxicity of NPs can be predicted without in vivo tests, while novel cell receptors could be identified from prominent proteins which play important key roles in the models. The ungoverned protein adsorption onto NPs may have generally negative effects such as rapid clearance from the bloodstream, hindrance of targeting capacity, and induction of toxicity. In contrast, controlling protein adsorption by modifying NPs with diverse functional proteins or tailoring appropriate NPs which favor selective endogenous peptides and proteins will bring promising therapeutic benefits in drug delivery and targeted cancer treatment. Keywords: protein-nanoparticle interaction, protein corona, exchange of adsorbed protein, toxicity reduction, predictive modeling, targeting drug delivery

  10. Protein Circular Dichroism Data Bank (PCDDB): data bank and website design.

    Science.gov (United States)

    Whitmore, Lee; Janes, Robert W; Wallace, B A

    2006-06-01

    The Protein Circular Dichroism Data Bank (PCDDB) is a new deposition data bank for validated circular dichroism spectra of biomacromolecules. Its aim is to be a resource for the structural biology and bioinformatics communities, providing open access and archiving facilities for circular dichroism and synchrotron radiation circular dichroism spectra. It is named in parallel with the Protein Data Bank (PDB), a long-existing valuable reference data bank for protein crystal and NMR structures. In this article, we discuss the design of the data bank structure and the deposition website located at http://pcddb.cryst.bbk.ac.uk. Our aim is to produce a flexible and comprehensive archive, which enables user-friendly spectral deposition and searching. In the case of a protein whose crystal structure and sequence are known, the PCDDB entry will be linked to the appropriate PDB and sequence data bank files, respectively. It is anticipated that the PCDDB will provide a readily accessible biophysical catalogue of information on folded proteins that may be of value in structural genomics programs, for quality control and archiving in industrial and academic labs, as a resource for programs developing spectroscopic structural analysis methods, and in bioinformatics studies. Copyright 2006 Wiley-Liss, Inc.

  11. New or improved computational methods and advanced reactor design

    International Nuclear Information System (INIS)

    Nakagawa, Masayuki; Takeda, Toshikazu; Ushio, Tadashi

    1997-01-01

    Nuclear computational method has been studied continuously up to date, as a fundamental technology supporting the nuclear development. At present, research on computational method according to new theory and the calculating method thought to be difficult to practise are also continued actively to find new development due to splendid improvement of features of computer. In Japan, many light water type reactors are now in operations, new computational methods are induced for nuclear design, and a lot of efforts are concentrated for intending to more improvement of economics and safety. In this paper, some new research results on the nuclear computational methods and their application to nuclear design of the reactor were described for introducing recent trend of the nuclear design of the reactor. 1) Advancement of the computational method, 2) Reactor core design and management of the light water reactor, and 3) Nuclear design of the fast reactor. (G.K.)

  12. Improved Energy Bound Accuracy Enhances the Efficiency of Continuous Protein Design

    OpenAIRE

    Roberts, Kyle E.; Donald, Bruce R.

    2015-01-01

    Flexibility and dynamics are important for protein function and a protein’s ability to accommodate amino acid substitutions. However, when computational protein design algorithms search over protein structures, the allowed flexibility is often reduced to a relatively small set of discrete side-chain and backbone conformations. While simplifications in scoring functions and protein flexibility are currently necessary to computationally search the vast protein sequence and conformational space,...

  13. Nonlinear optical methods for the analysis of protein nanocrystals and biological tissues

    Science.gov (United States)

    Dow, Ximeng You

    Structural biology underpins rational drug design and fundamental understanding of protein function. X-ray diffraction (XRD) has been the golden standard for solving for high-resolution protein structure. Second harmonic generation (SHG) microscopy has been developed by the Simpson lab as a sensitive, crystal-specific detection method for the identification of protein crystal and help optimize the crystallization condition. Protein nanocrystals has been widely used for structure determination of membrane proteins in serial femtosecond nanocrystallography. In this thesis work, novel nonlinear optical methods were developed to address the challenges associated with the detection and characterization of protein nanocrystals. SHG-correlation spectroscopy (SHG-CS) was developed to take advantage of the diffusing motion and retrieve the size distribution and crystal quality of the nanocrystals. Polarization-dependent SHG imaging technique was developed to measure the relative orientation as well as the internal structure of the sample. Two photon- excited fluorescence has been used in the Simpson lab as a complementary measurement besides the inherent SHG signal from the crystals. A novel instrumentation development was also introduced in this thesis work to greatly improve the speed of fluorescence lifetime imaging (FLIM).

  14. Computational design of chimeric protein libraries for directed evolution.

    Science.gov (United States)

    Silberg, Jonathan J; Nguyen, Peter Q; Stevenson, Taylor

    2010-01-01

    The best approach for creating libraries of functional proteins with large numbers of nondisruptive amino acid substitutions is protein recombination, in which structurally related polypeptides are swapped among homologous proteins. Unfortunately, as more distantly related proteins are recombined, the fraction of variants having a disrupted structure increases. One way to enrich the fraction of folded and potentially interesting chimeras in these libraries is to use computational algorithms to anticipate which structural elements can be swapped without disturbing the integrity of a protein's structure. Herein, we describe how the algorithm Schema uses the sequences and structures of the parent proteins recombined to predict the structural disruption of chimeras, and we outline how dynamic programming can be used to find libraries with a range of amino acid substitution levels that are enriched in variants with low Schema disruption.

  15. Mis-translation of a Computationally Designed Protein Yields an Exceptionally Stable Homodimer: Implications for Protein Engineering and Evolution.

    Energy Technology Data Exchange (ETDEWEB)

    Dantas, Gautam; Watters, Alexander L.; Lunde, Bradley; Eletr, Ziad; Isern, Nancy G.; Roseman, Toby; Lipfert, Jan; Doniach, Sebastian; Tompa, Martin; Kuhlman, Brian; Stoddard, Barry L.; Varani, Gabriele; Baker, David

    2006-10-06

    We recently used computational protein design to create an extremely stable, globular protein, Top7, with a sequence and fold not observed previously in nature. Since Top7 was created in the absence of genetic selection, it provides a rare opportunity to investigate aspects of the cellular protein production and surveillance machinery that are subject to natural selection. Here we show that a portion of the Top7 protein corresponding to the final 49 C-terminal residues is efficiently mistranslated and accumulates at high levels in E. coli. We used circular dichroism spectroscopy, size-exclusion chromatography, small-angle x-ray scattering, analytical ultra-centrifugation, and NMR spectroscopy to show that the resulting CFr protein adopts a compact, extremely-stable, obligate, symmetric, homo-dimeric structure. Based on the solution structure, we engineered an even more stable variant of CFr by disulfide-induced covalent circularisation that should be an excellent platform for design of novel functions. The accumulation of high levels of CFr exposes the high error rate of the protein translation machinery, and the rarity of correspondingly stable fragments in natural proteins implies a stringent evolutionary pressure against protein sub-fragments that can independently fold into stable structures. The symmetric self-association between two identical mistranslated CFr sub-units to generate an extremely stable structure parallels a mechanism for natural protein-fold evolution by modular recombination of stable protein sub-structures.

  16. Enhancing user experience design with an integrated storytelling method

    NARCIS (Netherlands)

    Peng, Qiong; Matterns, Jean Bernard; Marcus, A.

    2016-01-01

    Storytelling has been known as a service design method and been used broadly not only in service design but also in the context of user experience design. However, practitioners cannot yet fully appreciate the benefits of storytelling, and often confuse storytelling with storyboarding and scenarios.

  17. Methods for design flood estimation in South Africa | Smithers ...

    African Journals Online (AJOL)

    The estimation of design floods is necessary for the design of hydraulic structures and to quantify the risk of failure of the structures. Most of the methods used for design flood estimation in South Africa were developed in the late 1960s and early 1970s and are in need of updating with more than 40 years of additional data ...

  18. A Frequency Domain Design Method For Sampled-Data Compensators

    DEFF Research Database (Denmark)

    Niemann, Hans Henrik; Jannerup, Ole Erik

    1990-01-01

    A new approach to the design of a sampled-data compensator in the frequency domain is investigated. The starting point is a continuous-time compensator for the continuous-time system which satisfy specific design criteria. The new design method will graphically show how the discrete...

  19. Hybrid inverse design method for nonlifting bodies in incompressible flow

    CSIR Research Space (South Africa)

    Broughton, BA

    2006-11-01

    Full Text Available A methodology for the inverse design of non-lifting axisymmetric bodies in compressible flow is presented. In this method, an inverse design approach based on conformal mapping is used to design a set of airfoils in isolation. These airfoils...

  20. Integration of educational methods and physical settings: Design ...

    African Journals Online (AJOL)

    ... setting without having an architectural background. The theoretical framework of the research allows designers to consider key features and users' possible activities in High/ Scope settings and shape their designs accordingly. Keywords: daily activity; design; High/Scope education; interior space; teaching method ...

  1. Postmodern Software Design with NYAM: Not Yet Another Method

    NARCIS (Netherlands)

    Wieringa, Roelf J.; Broy, M.; Rumpe, B.

    1998-01-01

    This paper presents a conceptual toolbox for software specification and design that contains techniques from structured and object-oriented specification and design methods. The toolbox is called TRADE (Toolkit for Requirements and Design Engineering). The TRADE tools are used in teaching

  2. WSDM : A user-centred design method for web sites

    NARCIS (Netherlands)

    de Troyer, O.M.F.; Leune, C.J.

    1998-01-01

    WSDM is a user-centered method for the design of kiosk Web Sites. By explicitly starting from the requirements of the users or visitors, WSDM solves Web site problems that are primarily caused by that fact that a site has no underlying design at all, or that the design is mostly data-driven.

  3. Design and evaluate alginate nanoparticles as a protein delivery system

    Directory of Open Access Journals (Sweden)

    Saraei, F.

    2013-12-01

    Full Text Available In recent years, encapsulation of drugs and antigens in hydrogels, specifically in calcium alginate particles, is an interesting and practical technique that was developed widespread. It is well known that alginate solution, under proper conditions, can form suitable nanoparticles as a promising carrier system, for vaccine delivery. The aim of this study was to synthesis alginate nanoparticles as protein carrier and to evaluate the influence of various factors on nanoparticles properties. Alginate nanoparticles were prepared by ionic gelation method. Briefly, various concentrations of CaCl2 were added to different concentrations of sodium alginate dropwisly by homogenizing magnetically at 1300 rpm. The effects of homogenization time and (- rate were investigated on nanoparticle feature. Nanoparticles were characterized for their morphology and size distribution. Evaluation of loading capacity and loading efficiency of nanoparticles were performed by using various concentration of BSA. The concentration of 0.3%w/v sodium alginate and 0.1%w/v CaCl2 solution, homogenization time 45 min and homogenization rate 1300 rpm were observed as suitable condition - to prepare optimized nanoparticles. It can be concluded that the properties of nanoparticles are strongly dependent on the physicochemical conditions. The optimum concentrations of alginate and CaCl2and appropriate condition led to forming desirable nanoparticles that can be used as carrier for drug and vaccine delivery.

  4. Development of inelastic design method for liquid metal reactor plants

    International Nuclear Information System (INIS)

    Takahashi, Yukio; Take, Kohji; Kaguchi, Hitoshi; Fukuda, Yoshio; Uno, Tetsuro.

    1991-01-01

    Effective utilization of inelastic analysis in structural design assessment is expected to play an important role for avoiding too conservative design of liquid metal reactor plants. Studies have been conducted by the authors to develop a guideline for application of detailed inelastic analysis in design assessment. Both fundamental material characteristics tests and structural failure tests were conducted. Fundamental investigations were made on inelastic analysis method and creep-fatigue life prediction method based on the results of material characteristics tests. It was demonstrated through structural failure tests that the design method constructed based on these fundamental investigations can predict failure lives in structures subjected to cyclic thermal loadings with sufficient accuracy. (author)

  5. Interactive methods to involve users into workspace design process

    DEFF Research Database (Denmark)

    Souza da Conceição, Carolina; Broberg, Ole; Banke, Palle

    2013-01-01

    This paper addresses the question of whether the use of a combination of interactive methods involving workers can lead to a useful input to the (re)design of their workspace. The workbook and the layout design game methods were tested, and a comparison between their use and the ergonomic analysi...

  6. Valve cam design using numerical step-by-step method

    OpenAIRE

    Vasilyev, Aleksandr; Bakhracheva, Yuliya; Kabore, Ousman; Zelenskiy, Yuriy

    2014-01-01

    This article studies the numerical step-by-step method of cam profile design. The results of the study are used for designing the internal combustion engine valve gear. This method allows to profile the peak efficiency of cams in view of many restrictions, connected with valve gear serviceability and reliability.

  7. Human-centred Methods of Social and Technical Design

    DEFF Research Database (Denmark)

    Rasmussen, Lauge Baungaard

    Different inderstandings of design are presented.The historical background of human-centred designis described.Methods of social shaping are described in detailand the author's research experiences with using these methods in differentinternational projects presented and a model tointegrate...... technical and social perspective of design is suggested....

  8. Methods of designing and manufacturing a heat exchanger for the ...

    African Journals Online (AJOL)

    The article describes the method of calculation, design and manufacture of the the plate heat exchanger for the gas turbine plants with heat recovery. We represented the method of threedimensional calculation, which allowed conducting a virtual experiment and clarifying the design of the heat exchanger for the given ...

  9. Innovative design method of automobile profile based on Fourier descriptor

    Science.gov (United States)

    Gao, Shuyong; Fu, Chaoxing; Xia, Fan; Shen, Wei

    2017-10-01

    Aiming at the innovation of the contours of automobile side, this paper presents an innovative design method of vehicle side profile based on Fourier descriptor. The design flow of this design method is: pre-processing, coordinate extraction, standardization, discrete Fourier transform, simplified Fourier descriptor, exchange descriptor innovation, inverse Fourier transform to get the outline of innovative design. Innovative concepts of the innovative methods of gene exchange among species and the innovative methods of gene exchange among different species are presented, and the contours of the innovative design are obtained separately. A three-dimensional model of a car is obtained by referring to the profile curve which is obtained by exchanging xenogeneic genes. The feasibility of the method proposed in this paper is verified by various aspects.

  10. Can Natural Proteins Designed with ‘Inverted’ Peptide Sequences Adopt Native-Like Protein Folds?

    Science.gov (United States)

    Sridhar, Settu; Guruprasad, Kunchur

    2014-01-01

    We have carried out a systematic computational analysis on a representative dataset of proteins of known three-dimensional structure, in order to evaluate whether it would possible to ‘swap’ certain short peptide sequences in naturally occurring proteins with their corresponding ‘inverted’ peptides and generate ‘artificial’ proteins that are predicted to retain native-like protein fold. The analysis of 3,967 representative proteins from the Protein Data Bank revealed 102,677 unique identical inverted peptide sequence pairs that vary in sequence length between 5–12 and 18 amino acid residues. Our analysis illustrates with examples that such ‘artificial’ proteins may be generated by identifying peptides with ‘similar structural environment’ and by using comparative protein modeling and validation studies. Our analysis suggests that natural proteins may be tolerant to accommodating such peptides. PMID:25210740

  11. A dielectrophoresis-impedance method for protein detection and analysis

    Directory of Open Access Journals (Sweden)

    Ahmad Sabry Mohamad

    2017-01-01

    Full Text Available Dielectrophoresis (DEP has increasingly been used for the assessment of the electrical properties of molecular scale objects including proteins, DNA, nanotubes and nanowires. However, whilst techniques have been developed for the electrical characterisation of frequency-dependent DEP response, biomolecular study is usually limited to observation using fluorescent markers, limiting its applicability as a characterisation tool. In this paper we present a label-free, impedance-based method of characterisation applied to the determination of the electrical properties of colloidal protein molecules, specifically Bovine Serum Albumin (BSA. By monitoring the impedance between electrodes as proteins collect, it is shown to be possible to observe multi-dispersion behaviour. A DEP dispersion exhibited at 400 kHz is attributable to the orientational dispersion of the molecule, whilst a second, higher-frequency dispersion is attributed to a Maxwell-Wagner type dispersion; changes in behaviour with medium conductivity suggest that this is strongly influenced by the electrical double layer surrounding the molecule.

  12. Methods of measuring Protein Disulfide Isomerase activity: a critical overview

    Science.gov (United States)

    Watanabe, Monica; Laurindo, Francisco; Fernandes, Denise

    2014-09-01

    Protein disulfide isomerase is an essential redox chaperone from the endoplasmic reticulum (ER) and is responsible for correct disulfide bond formation in nascent proteins. PDI is also found in other cellular locations in the cell, particularly the cell surface. Overall, PDI contributes to ER and global cell redox homeostasis and signaling. The knowledge about PDI structure and function progressed substantially based on in vitro studies using recombinant PDI and chimeric proteins. In these experimental scenarios, PDI reductase and chaperone activities are readily approachable. In contrast, assays to measure PDI isomerase activity, the hallmark of PDI family, are more complex. Assessment of PDI roles in cells and tissues mainly relies on gain- or loss-of-function studies. However, there is limited information regarding correlation of experimental readouts with the distinct types of PDI activities. In this mini-review, we evaluate the main methods described for measuring the different kinds of PDI activity: thiol reductase, thiol oxidase, thiol isomerase and chaperone. We emphasize the need to use appropriate controls and the role of critical interferents (e.g., detergent, presence of reducing agents). We also discuss the translation of results from in vitro studies with purified recombinant PDI to cellular and tissue samples, with critical comments on the interpretation of results.

  13. Spectral methods for study of the G-protein-coupled receptor rhodopsin. II. Magnetic resonance methods

    Science.gov (United States)

    Struts, A. V.; Barmasov, A. V.; Brown, M. F.

    2016-02-01

    This article continues our review of spectroscopic studies of G-protein-coupled receptors. Magnetic resonance methods including electron paramagnetic resonance (EPR) and nuclear magnetic resonance (NMR) provide specific structural and dynamical data for the protein in conjunction with optical methods (vibrational, electronic spectroscopy) as discussed in the accompanying article. An additional advantage is the opportunity to explore the receptor proteins in the natural membrane lipid environment. Solid-state 2H and 13C NMR methods yield information about both the local structure and dynamics of the cofactor bound to the protein and its light-induced changes. Complementary site-directed spin-labeling studies monitor the structural alterations over larger distances and correspondingly longer time scales. A multiscale reaction mechanism describes how local changes of the retinal cofactor unlock the receptor to initiate large-scale conformational changes of rhodopsin. Activation of the G-protein-coupled receptor involves an ensemble of conformational substates within the rhodopsin manifold that characterize the dynamically active receptor.

  14. DomPep--a general method for predicting modular domain-mediated protein-protein interactions.

    Directory of Open Access Journals (Sweden)

    Lei Li

    Full Text Available Protein-protein interactions (PPIs are frequently mediated by the binding of a modular domain in one protein to a short, linear peptide motif in its partner. The advent of proteomic methods such as peptide and protein arrays has led to the accumulation of a wealth of interaction data for modular interaction domains. Although several computational programs have been developed to predict modular domain-mediated PPI events, they are often restricted to a given domain type. We describe DomPep, a method that can potentially be used to predict PPIs mediated by any modular domains. DomPep combines proteomic data with sequence information to achieve high accuracy and high coverage in PPI prediction. Proteomic binding data were employed to determine a simple yet novel parameter Ligand-Binding Similarity which, in turn, is used to calibrate Domain Sequence Identity and Position-Weighted-Matrix distance, two parameters that are used in constructing prediction models. Moreover, DomPep can be used to predict PPIs for both domains with experimental binding data and those without. Using the PDZ and SH2 domain families as test cases, we show that DomPep can predict PPIs with accuracies superior to existing methods. To evaluate DomPep as a discovery tool, we deployed DomPep to identify interactions mediated by three human PDZ domains. Subsequent in-solution binding assays validated the high accuracy of DomPep in predicting authentic PPIs at the proteome scale. Because DomPep makes use of only interaction data and the primary sequence of a domain, it can be readily expanded to include other types of modular domains.

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

    Science.gov (United States)

    Gainza-Cirauqui, Pablo; Correia, Bruno Emanuel

    2018-05-02

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

  16. An efficient and rapid method for protein detection with an example ...

    African Journals Online (AJOL)

    AJL

    2012-05-15

    May 15, 2012 ... protein expressed in Esherichia coli by staining and destaining in under 30 min. The CMW method .... the saturated solutions reached a state of dynamic ... M, Protein molecular marker; 1, the control vector; 2, the SQR protein.

  17. Design of cooling towers by the effectiveness-NTU method

    International Nuclear Information System (INIS)

    Jaber, H.; Webb, R.L.

    1989-01-01

    This paper develops the effectiveness-NTU, number of transfer units, design method for cooling towers. The definitions for effectiveness and NTU are totally consistent with the fundamental definitions used in heat exchanger design. Sample calculations are presented for counter and crossflow cooling towers. Using the proper definitions, a person competent in heat transfer design can easily use the same basic method to design a cooling tower of counter, cross, or parallel flow configuration. The problems associated with the curvature of the saturated air enthalpy line are also treated. A one-increment design ignores the effect of this curvature. Increased precision can be obtained by dividing the cooling range into two or more increments. The standard effectiveness-NYU method is then used for each of the increments. Calculations are presented to define the error associated with different numbers of increments. This defines the number of increments required to attain a desired degree of precision. The authors also summarize the LMED method introduced by Berman, and show that this is totally consistent with the effectiveness-NTU method. Hence, using proper and consistent terms, heat exchanger designers are shown how to use either the standard Log-Mean Enthalpy Method (LMED) or effectiveness-NTU design methods to design cooling towers

  18. Fragment molecular orbital method for studying lanthanide interactions with proteins

    Energy Technology Data Exchange (ETDEWEB)

    Tsushima, Satoru [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). Biophysics; Komeiji, Y. [National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba (Japan); Mochizuki, Y. [Rikkyo Univ., Tokyo (Japan)

    2017-06-01

    The binding affinity of the calcium-binding protein calmodulin towards Eu{sup 3+} was studied as a model for lanthanide protein interactions in the large family of ''EF-hand'' calcium-binding proteins.

  19. Application of analytical target cascading method in multidisciplinary design optimization of ship conceptual design

    Directory of Open Access Journals (Sweden)

    WANG Jian

    2017-10-01

    Full Text Available [Objectives] Ship conceptual design requires the coordination of many different disciplines for comprehensive optimization, which presents a complicated system design problem affecting several fields of technology. However, the development of overall ship design is relatively slow compared with other subjects. [Methods] The decomposition and coordination strategy of ship design is presented, and the analytical target cascading (ATC method is applied to the multidisciplinary design optimization of the conceptual design phase of ships on this basis. A tank ship example covering the 5 disciplines of buoyancy and stability, rapidity, maneuverability, capacity and economy is established to illustrate the analysis process in the present study. [Results] The results demonstrate the stability, convergence and validity of the ATC method in dealing with the complex coupling effect occurring in ship conceptual design.[Conclusions] The proposed method provides an effective basis for optimization of ship conceptual design.

  20. 77 FR 60985 - Ambient Air Monitoring Reference and Equivalent Methods: Designation of Three New Equivalent Methods

    Science.gov (United States)

    2012-10-05

    ... Methods: Designation of Three New Equivalent Methods AGENCY: Environmental Protection Agency. ACTION: Notice of the designation of three new equivalent methods for monitoring ambient air quality. SUMMARY... equivalent methods, one for measuring concentrations of PM 2.5 , one for measuring concentrations of PM 10...

  1. A comprehensive benchmark of kernel methods to extract protein-protein interactions from literature.

    Directory of Open Access Journals (Sweden)

    Domonkos Tikk

    Full Text Available The most important way of conveying new findings in biomedical research is scientific publication. Extraction of protein-protein interactions (PPIs reported in scientific publications is one of the core topics of text mining in the life sciences. Recently, a new class of such methods has been proposed - convolution kernels that identify PPIs using deep parses of sentences. However, comparing published results of different PPI extraction methods is impossible due to the use of different evaluation corpora, different evaluation metrics, different tuning procedures, etc. In this paper, we study whether the reported performance metrics are robust across different corpora and learning settings and whether the use of deep parsing actually leads to an increase in extraction quality. Our ultimate goal is to identify the one method that performs best in real-life scenarios, where information extraction is performed on unseen text and not on specifically prepared evaluation data. We performed a comprehensive benchmarking of nine different methods for PPI extraction that use convolution kernels on rich linguistic information. Methods were evaluated on five different public corpora using cross-validation, cross-learning, and cross-corpus evaluation. Our study confirms that kernels using dependency trees generally outperform kernels based on syntax trees. However, our study also shows that only the best kernel methods can compete with a simple rule-based approach when the evaluation prevents information leakage between training and test corpora. Our results further reveal that the F-score of many approaches drops significantly if no corpus-specific parameter optimization is applied and that methods reaching a good AUC score often perform much worse in terms of F-score. We conclude that for most kernels no sensible estimation of PPI extraction performance on new text is possible, given the current heterogeneity in evaluation data. Nevertheless, our study

  2. Protein thermal stability enhancement by designing salt bridges: a combined computational and experimental study.

    Directory of Open Access Journals (Sweden)

    Chi-Wen Lee

    Full Text Available Protein thermal stability is an important factor considered in medical and industrial applications. Many structural characteristics related to protein thermal stability have been elucidated, and increasing salt bridges is considered as one of the most efficient strategies to increase protein thermal stability. However, the accurate simulation of salt bridges remains difficult. In this study, a novel method for salt-bridge design was proposed based on the statistical analysis of 10,556 surface salt bridges on 6,493 X-ray protein structures. These salt bridges were first categorized based on pairing residues, secondary structure locations, and Cα-Cα distances. Pairing preferences generalized from statistical analysis were used to construct a salt-bridge pair index and utilized in a weighted electrostatic attraction model to find the effective pairings for designing salt bridges. The model was also coupled with B-factor, weighted contact number, relative solvent accessibility, and conservation prescreening to determine the residues appropriate for the thermal adaptive design of salt bridges. According to our method, eight putative salt-bridges were designed on a mesophilic β-glucosidase and 24 variants were constructed to verify the predictions. Six putative salt-bridges leaded to the increase of the enzyme thermal stability. A significant increase in melting temperature of 8.8, 4.8, 3.7, 1.3, 1.2, and 0.7°C of the putative salt-bridges N437K-D49, E96R-D28, E96K-D28, S440K-E70, T231K-D388, and Q277E-D282 was detected, respectively. Reversing the polarity of T231K-D388 to T231D-D388K resulted in a further increase in melting temperatures by 3.6°C, which may be caused by the transformation of an intra-subunit electrostatic interaction into an inter-subunit one depending on the local environment. The combination of the thermostable variants (N437K, E96R, T231D and D388K generated a melting temperature increase of 15.7°C. Thus, this study

  3. Development of chelate tagging method of protein at low temperature

    International Nuclear Information System (INIS)

    Oida, Shigeru; Sekiya, Keizo

    1999-01-01

    This study aimed at development of a protein labelling method at a low temperature, available for functional proteins, such as antibodies and enzymes mostly unstable at high temperatures. A solution of anti-mouse IgG antibody added with EDTA was incubated with 51 CrCl 3 at 4degC for 24 hours. After stopping the reaction with 100-fold amount of EDTA-2Na, the solution was fractionated into antibody fraction and metal fraction by HPLC. After incubation, non-specific Cr adsorption on the antibody in no relation to the chelate reagent was chased with 10-fold amount of CrCl 3 . To remove free Cr, the sample solution was incubated with 10 to 50-fold ICB-EDTA solution containing N,N-dimethyl-formamide. Then, the amount of Cr-labelling on the antibody was determined. In Western-blotting, chick actin was applied onto SDS-polyacrylamide gel electrophoresis. One part of the lane was stained with brilliant-blue and the other was transferred on nitrocellulose membrane by semi-dry method and stained with panceau-S. Anti-actin monoclonal antibody and anti-mouse IgG antibody were used as the first antibody and the second one, respectively. When incubated with ICB-EDTA for 3 days, labelling reached the maximum level. Although labelling of the second antibody was performed with maleimido-C 3 -benzyl EDTA and 45 Ca as a substitute for 51 Cr, the rate of labelling was lower than the rate for a combination of ICB-EDTA and 51 Cr. Autoradiography of the anti-mouse IgG preparation after SDS-acrylamide gel electrophoresis revealed that radioactivity was detected on the site of H-chain but not L-chain. This indicates that 51 Cr labelling of protein is stable even under the conditions of SDS denaturation. (M.N.)

  4. Expanding color design methods for architecture and allied disciplines

    Science.gov (United States)

    Linton, Harold E.

    2002-06-01

    The color design processes of visual artists, architects, designers, and theoreticians included in this presentation reflect the practical role of color in architecture. What the color design professional brings to the architectural design team is an expertise and rich sensibility made up of a broad awareness and a finely tuned visual perception. This includes a knowledge of design and its history, expertise with industrial color materials and their methods of application, an awareness of design context and cultural identity, a background in physiology and psychology as it relates to human welfare, and an ability to problem-solve and respond creatively to design concepts with innovative ideas. The broadening of the definition of the colorists's role in architectural design provides architects, artists and designers with significant opportunities for continued professional and educational development.

  5. Designing protein-based biomaterials for medical applications.

    Science.gov (United States)

    Gagner, Jennifer E; Kim, Wookhyun; Chaikof, Elliot L

    2014-04-01

    Biomaterials produced by nature have been honed through billions of years, evolving exquisitely precise structure-function relationships that scientists strive to emulate. Advances in genetic engineering have facilitated extensive investigations to determine how changes in even a single peptide within a protein sequence can produce biomaterials with unique thermal, mechanical and biological properties. Elastin, a naturally occurring protein polymer, serves as a model protein to determine the relationship between specific structural elements and desirable material characteristics. The modular, repetitive nature of the protein facilitates the formation of well-defined secondary structures with the ability to self-assemble into complex three-dimensional architectures on a variety of length scales. Furthermore, many opportunities exist to incorporate other protein-based motifs and inorganic materials into recombinant protein-based materials, extending the range and usefulness of these materials in potential biomedical applications. Elastin-like polypeptides (ELPs) can be assembled into 3-D architectures with precise control over payload encapsulation, mechanical and thermal properties, as well as unique functionalization opportunities through both genetic and enzymatic means. An overview of current protein-based materials, their properties and uses in biomedicine will be provided, with a focus on the advantages of ELPs. Applications of these biomaterials as imaging and therapeutic delivery agents will be discussed. Finally, broader implications and future directions of these materials as diagnostic and therapeutic systems will be explored. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Review of design optimization methods for turbomachinery aerodynamics

    Science.gov (United States)

    Li, Zhihui; Zheng, Xinqian

    2017-08-01

    In today's competitive environment, new turbomachinery designs need to be not only more efficient, quieter, and ;greener; but also need to be developed at on much shorter time scales and at lower costs. A number of advanced optimization strategies have been developed to achieve these requirements. This paper reviews recent progress in turbomachinery design optimization to solve real-world aerodynamic problems, especially for compressors and turbines. This review covers the following topics that are important for optimizing turbomachinery designs. (1) optimization methods, (2) stochastic optimization combined with blade parameterization methods and the design of experiment methods, (3) gradient-based optimization methods for compressors and turbines and (4) data mining techniques for Pareto Fronts. We also present our own insights regarding the current research trends and the future optimization of turbomachinery designs.

  7. Interpretation of biological and mechanical variations between the Lowry versus Bradford method for protein quantification

    OpenAIRE

    Tzong-Shi Lu; Szu-Yu Yiao; Kenneth Lim; Roderick V. Jensen; Li-Li Hsiao

    2010-01-01

    Background: The identification of differences in protein expression resulting from methodical variations is an essential component to the interpretation of true, biologically significant results. Aims: We used the Lowry and Bradford methods- two most commonly used methods for protein quantification, to assess whether differential protein expressions are a result of true biological or methodical variations. Material & Methods: Differential protein expression patterns was assessed by western bl...

  8. Rational design of new materials using recombinant structural proteins: Current state and future challenges.

    Science.gov (United States)

    Sutherland, Tara D; Huson, Mickey G; Rapson, Trevor D

    2018-01-01

    Sequence-definable polymers are seen as a prerequisite for design of future materials, with many polymer scientists regarding such polymers as the holy grail of polymer science. Recombinant proteins are sequence-defined polymers. Proteins are dictated by DNA templates and therefore the sequence of amino acids in a protein is defined, and molecular biology provides tools that allow redesign of the DNA as required. Despite this advantage, proteins are underrepresented in materials science. In this publication we investigate the advantages and limitations of using proteins as templates for rational design of new materials. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  9. Theory and design methods of special space orbits

    CERN Document Server

    Zhang, Yasheng; Zhou, Haijun

    2017-01-01

    This book focuses on the theory and design of special space orbits. Offering a systematic and detailed introduction to the hovering orbit, spiral cruising orbit, multi-target rendezvous orbit, initiative approaching orbit, responsive orbit and earth pole-sitter orbit, it also discusses the concept, theory, design methods and application of special space orbits, particularly the design and control method based on kinematics and astrodynamics. In addition the book presents the latest research and its application in space missions. It is intended for researchers, engineers and postgraduates, especially those working in the fields of orbit design and control, as well as space-mission planning and research.

  10. Multi-objective optimization design method of radiation shielding

    International Nuclear Information System (INIS)

    Yang Shouhai; Wang Weijin; Lu Daogang; Chen Yixue

    2012-01-01

    Due to the shielding design goals of diversification and uncertain process of many factors, it is necessary to develop an optimization design method of intelligent shielding by which the shielding scheme selection will be achieved automatically and the uncertainties of human impact will be reduced. For economical feasibility to achieve a radiation shielding design for automation, the multi-objective genetic algorithm optimization of screening code which combines the genetic algorithm and discrete-ordinate method was developed to minimize the costs, size, weight, and so on. This work has some practical significance for gaining the optimization design of shielding. (authors)

  11. Simple design of slanted grating with simplified modal method.

    Science.gov (United States)

    Li, Shubin; Zhou, Changhe; Cao, Hongchao; Wu, Jun

    2014-02-15

    A simplified modal method (SMM) is presented that offers a clear physical image for subwavelength slanted grating. The diffraction characteristic of the slanted grating under Littrow configuration is revealed by the SMM as an equivalent rectangular grating, which is in good agreement with rigorous coupled-wave analysis. Based on the equivalence, we obtained an effective analytic solution for simplifying the design and optimization of a slanted grating. It offers a new approach for design of the slanted grating, e.g., a 1×2 beam splitter can be easily designed. This method should be helpful for designing various new slanted grating devices.

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

    Science.gov (United States)

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

    2018-05-01

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

  13. Design Method for Channel Diffusers of Centrifugal Compressors

    Directory of Open Access Journals (Sweden)

    Mykola Kalinkevych

    2013-01-01

    Full Text Available The design method for channel diffusers of centrifugal compressors, which is based on the solving of the inverse problem of gas dynamics, is presented in the paper. The concept of the design is to provide high pressure recovery of the diffuser by assuming the preseparation condition of the boundary layer along one of the channel surfaces. The channel diffuser was designed with the use of developed method to replace the vaned diffuser of the centrifugal compressor model stage. The numerical simulation of the diffusers was implemented by means of CFD software. Obtained gas dynamic characteristics of the designed diffuser were compared to the base vaned diffuser of the compressor stage.

  14. Formal methods in design and verification of functional specifications

    International Nuclear Information System (INIS)

    Vaelisuo, H.

    1995-01-01

    It is claimed that formal methods should be applied already when specifying the functioning of the control/monitoring system, i.e. when planning how to implement the desired operation of the plant. Formal methods are seen as a way to mechanize and thus automate part of the planning. All mathematical methods which can be applied on related problem solving should be considered as formal methods. Because formal methods can only support the designer, not replace him/her, they must be integrated into a design support tool. Such a tool must also aid the designer in getting the correct conception of the plant and its behaviour. The use of a hypothetic design support tool is illustrated to clarify the requirements such a tool should fulfill. (author). 3 refs, 5 figs

  15. Designing adaptive intensive interventions using methods from engineering.

    Science.gov (United States)

    Lagoa, Constantino M; Bekiroglu, Korkut; Lanza, Stephanie T; Murphy, Susan A

    2014-10-01

    Adaptive intensive interventions are introduced, and new methods from the field of control engineering for use in their design are illustrated. A detailed step-by-step explanation of how control engineering methods can be used with intensive longitudinal data to design an adaptive intensive intervention is provided. The methods are evaluated via simulation. Simulation results illustrate how the designed adaptive intensive intervention can result in improved outcomes with less treatment by providing treatment only when it is needed. Furthermore, the methods are robust to model misspecification as well as the influence of unobserved causes. These new methods can be used to design adaptive interventions that are effective yet reduce participant burden. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  16. Identification of discriminant proteins through antibody profiling, methods and apparatus for identifying an individual

    Science.gov (United States)

    Thompson, Vicki S; Lacey, Jeffrey A; Gentillon, Cynthia A; Apel, William A

    2015-03-03

    A method for determining a plurality of proteins for discriminating and positively identifying an individual based from a biological sample. The method may include profiling a biological sample from a plurality of individuals against a protein array including a plurality of proteins. The protein array may include proteins attached to a support in a preselected pattern such that locations of the proteins are known. The biological sample may be contacted with the protein array such that a portion of antibodies in the biological sample reacts with and binds to the proteins forming immune complexes. A statistical analysis method, such as discriminant analysis, may be performed to determine discriminating proteins for distinguishing individuals. Proteins of interest may be used to form a protein array. Such a protein array may be used, for example, to compare a forensic sample from an unknown source with a sample from a known source.

  17. Identification of discriminant proteins through antibody profiling, methods and apparatus for identifying an individual

    Energy Technology Data Exchange (ETDEWEB)

    Apel, William A.; Thompson, Vicki S; Lacey, Jeffrey A.; Gentillon, Cynthia A.

    2016-08-09

    A method for determining a plurality of proteins for discriminating and positively identifying an individual based from a biological sample. The method may include profiling a biological sample from a plurality of individuals against a protein array including a plurality of proteins. The protein array may include proteins attached to a support in a preselected pattern such that locations of the proteins are known. The biological sample may be contacted with the protein array such that a portion of antibodies in the biological sample reacts with and binds to the proteins forming immune complexes. A statistical analysis method, such as discriminant analysis, may be performed to determine discriminating proteins for distinguishing individuals. Proteins of interest may be used to form a protein array. Such a protein array may be used, for example, to compare a forensic sample from an unknown source with a sample from a known source.

  18. FireProt: web server for automated design of thermostable proteins

    Science.gov (United States)

    Musil, Milos; Stourac, Jan; Brezovsky, Jan; Prokop, Zbynek; Zendulka, Jaroslav; Martinek, Tomas

    2017-01-01

    Abstract There is a continuous interest in increasing proteins stability to enhance their usability in numerous biomedical and biotechnological applications. A number of in silico tools for the prediction of the effect of mutations on protein stability have been developed recently. However, only single-point mutations with a small effect on protein stability are typically predicted with the existing tools and have to be followed by laborious protein expression, purification, and characterization. Here, we present FireProt, a web server for the automated design of multiple-point thermostable mutant proteins that combines structural and evolutionary information in its calculation core. FireProt utilizes sixteen tools and three protein engineering strategies for making reliable protein designs. The server is complemented with interactive, easy-to-use interface that allows users to directly analyze and optionally modify designed thermostable mutants. FireProt is freely available at http://loschmidt.chemi.muni.cz/fireprot. PMID:28449074

  19. A design method of oscillatory De-Qing circuit

    International Nuclear Information System (INIS)

    Feng Wenquan

    1988-01-01

    With some particular advantages the oscillatory De-Qing circuit now is widely used. However its design is very complex. By means of a quantitative analysis for this circuit a group of design formulas is obtained. According to these design formulas the maximum allowable charging inductance L c , the De-Qing network resistance R and capacitance C can easily be determined, if the PFN capacitance C N , the maximum pulse frequency F max , and percentage regulation η are given. Simple and direct formulas for specific situation are listed. Finally, a design example is given and a comparison with experimental result is made, which shows that the design method is feasible and reliable

  20. Development of probabilistic fast reactor fuel design method

    International Nuclear Information System (INIS)

    Ozawa, Takayuki

    1997-01-01

    Under the current method of evaluating fuel robustness in FBR fuel rod design, a variety of uncertain quantities including fuel production tolerance and power density are estimated conservatively. In the future, in order to proceed with improvements in the FBR core's performance and optimize the fuel's specifications, a rationalization of fuel design tolerance is required. Among the measures aimed at realizing this rationalization, the introduction of a probabilistic fast reactor fuel design method is currently under consideration. I have developed a probabilistic fast reactor fuel design code named BORNFREE, in order to make use of this method in FBR fuel design. At the same time, I have carried out a trial calculation of the cladding stress using this code and made a study and an evaluation of the possibility of employing tolerance rationalization in fuel rod design. In this paper, I provide an outline description of BORNFREE and report the results of the above study and evaluation. After performing cladding stress trial calculations using the probabilistic method, I was able to confirm that this method promises more rational design evaluation results than the conventional deterministic method. (author)

  1. Design of nuclear power generation plants adopting model engineering method

    International Nuclear Information System (INIS)

    Waki, Masato

    1983-01-01

    The utilization of model engineering as the method of design has begun about ten years ago in nuclear power generation plants. By this method, the result of design can be confirmed three-dimensionally before actual production, and it is the quick and sure method to meet the various needs in design promptly. The adoption of models aims mainly at the improvement of the quality of design since the high safety is required for nuclear power plants in spite of the complex structure. The layout of nuclear power plants and piping design require the model engineering to arrange rationally enormous quantity of things in a limited period. As the method of model engineering, there are the use of check models and of design models, and recently, the latter method has been mainly taken. The procedure of manufacturing models and engineering is explained. After model engineering has been completed, the model information must be expressed in drawings, and the automation of this process has been attempted by various methods. The computer processing of design is in progress, and its role is explained (CAD system). (Kako, I.)

  2. A protein relational database and protein family knowledge bases to facilitate structure-based design analyses.

    Science.gov (United States)

    Mobilio, Dominick; Walker, Gary; Brooijmans, Natasja; Nilakantan, Ramaswamy; Denny, R Aldrin; Dejoannis, Jason; Feyfant, Eric; Kowticwar, Rupesh K; Mankala, Jyoti; Palli, Satish; Punyamantula, Sairam; Tatipally, Maneesh; John, Reji K; Humblet, Christine

    2010-08-01

    The Protein Data Bank is the most comprehensive source of experimental macromolecular structures. It can, however, be difficult at times to locate relevant structures with the Protein Data Bank search interface. This is particularly true when searching for complexes containing specific interactions between protein and ligand atoms. Moreover, searching within a family of proteins can be tedious. For example, one cannot search for some conserved residue as residue numbers vary across structures. We describe herein three databases, Protein Relational Database, Kinase Knowledge Base, and Matrix Metalloproteinase Knowledge Base, containing protein structures from the Protein Data Bank. In Protein Relational Database, atom-atom distances between protein and ligand have been precalculated allowing for millisecond retrieval based on atom identity and distance constraints. Ring centroids, centroid-centroid and centroid-atom distances and angles have also been included permitting queries for pi-stacking interactions and other structural motifs involving rings. Other geometric features can be searched through the inclusion of residue pair and triplet distances. In Kinase Knowledge Base and Matrix Metalloproteinase Knowledge Base, the catalytic domains have been aligned into common residue numbering schemes. Thus, by searching across Protein Relational Database and Kinase Knowledge Base, one can easily retrieve structures wherein, for example, a ligand of interest is making contact with the gatekeeper residue.

  3. Principles for designing proteins with cavities formed by curved β sheets

    Energy Technology Data Exchange (ETDEWEB)

    Marcos, Enrique; Basanta, Benjamin; Chidyausiku, Tamuka M.; Tang, Yuefeng; Oberdorfer, Gustav; Liu, Gaohua; Swapna, G. V. T.; Guan, Rongjin; Silva, Daniel-Adriano; Dou, Jiayi; Pereira, Jose Henrique; Xiao, Rong; Sankaran, Banumathi; Zwart, Peter H.; Montelione, Gaetano T.; Baker, David

    2017-01-12

    Active sites and ligand-binding cavities in native proteins are often formed by curved β sheets, and the ability to control β-sheet curvature would allow design of binding proteins with cavities customized to specific ligands. Toward this end, we investigated the mechanisms controlling β-sheet curvature by studying the geometry of β sheets in naturally occurring protein structures and folding simulations. The principles emerging from this analysis were used to design, de novo, a series of proteins with curved β sheets topped with α helices. Nuclear magnetic resonance and crystal structures of the designs closely match the computational models, showing that β-sheet curvature can be controlled with atomic-level accuracy. Our approach enables the design of proteins with cavities and provides a route to custom design ligand-binding and catalytic sites.

  4. Optical description and design method with annularly stitched aspheric surface.

    Science.gov (United States)

    Cheng, De-Wen; Chen, Xue-Jiao; Xu, Chen; Hu, Yuan; Wang, Yong-Tian

    2015-12-01

    The relentless pressure for designs with new optical functions, small volume, and light weight has greatly increased the importance of aspheric surfaces. In this paper, we propose an annularly stitched aspheric surface (ASAS) description method to increase the freedom and flexibility of imaging system design. The rotationally symmetric ASAS consists of a circular central zone and one or more annular zones. Two neighboring zones are constrained to have the same derivatives on their joint curve, and this means the ASAS is C1 continuous. This finding is proved and verified by the mathematical deduction of the surface formulas. Two optimization strategies and two design methods with the C1 continuous constraints are also discussed. This surface can greatly facilitate the design and even achieve some previously impossible designs without increasing the fabrication difficulty. Two different systems with the proposed ASAS are optimized and the results are presented. The design results verified the practicability of the ASAS.

  5. Single-Case Designs and Qualitative Methods: Applying a Mixed Methods Research Perspective

    Science.gov (United States)

    Hitchcock, John H.; Nastasi, Bonnie K.; Summerville, Meredith

    2010-01-01

    The purpose of this conceptual paper is to describe a design that mixes single-case (sometimes referred to as single-subject) and qualitative methods, hereafter referred to as a single-case mixed methods design (SCD-MM). Minimal attention has been given to the topic of applying qualitative methods to SCD work in the literature. These two…

  6. Implementing Adaptive Educational Methods with IMS Learning Design

    NARCIS (Netherlands)

    Specht, Marcus; Burgos, Daniel

    2006-01-01

    Please, cite this publication as: Specht, M. & Burgos, D. (2006). Implementing Adaptive Educational Methods with IMS Learning Design. Proceedings of Adaptive Hypermedia. June, Dublin, Ireland. Retrieved June 30th, 2006, from http://dspace.learningnetworks.org

  7. Advanced Topology Optimization Methods for Conceptual Architectural Design

    DEFF Research Database (Denmark)

    Aage, Niels; Amir, Oded; Clausen, Anders

    2015-01-01

    This paper presents a series of new, advanced topology optimization methods, developed specifically for conceptual architectural design of structures. The proposed computational procedures are implemented as components in the framework of a Grasshopper plugin, providing novel capacities...

  8. Advanced Topology Optimization Methods for Conceptual Architectural Design

    DEFF Research Database (Denmark)

    Aage, Niels; Amir, Oded; Clausen, Anders

    2014-01-01

    This paper presents a series of new, advanced topology optimization methods, developed specifically for conceptual architectural design of structures. The proposed computational procedures are implemented as components in the framework of a Grasshopper plugin, providing novel capacities...

  9. Overview of the South African mechanistic pavement design analysis method

    CSIR Research Space (South Africa)

    Theyse, HL

    1996-01-01

    Full Text Available A historical overview of the South African mechanistic pavement design method, from its development in the early 1970s to the present, is presented. Material characterization, structural analysis, and pavement life prediction are discussed...

  10. Methods for design flood estimation in South Africa

    African Journals Online (AJOL)

    2012-07-04

    Jul 4, 2012 ... 1970s and are in need of updating with more than 40 years of additional data ... This paper reviews methods used for design flood estimation in South Africa and .... transposition of past experience, or a deterministic approach,.

  11. Multivariable control in nuclear power stations -survey of design methods

    International Nuclear Information System (INIS)

    Mcmorran, P.D.

    1979-12-01

    The development of larger nuclear generating stations increases the importance of dynamic interaction between controllers, because each control action may affect several plant outputs. Multivariable control provides the techniques to design controllers which perform well under these conditions. This report is a foundation for further work on the application of multivariable control in AECL. It covers the requirements of control and the fundamental mathematics used, then reviews the most important linear methods, based on both state-space and frequency-response concepts. State-space methods are derived from analysis of the system differential equations, while frequency-response methods use the input-output transfer function. State-space methods covered include linear-quadratic optimal control, pole shifting, and the theory of state observers and estimators. Frequency-response methods include the inverse Nyquist array method, and classical non-interactive techniques. Transfer-function methods are particularly emphasized since they can incorporate ill-defined design criteria. The underlying concepts, and the application strengths and weaknesses of each design method are presented. A review of significant applications is also given. It is concluded that the inverse Nyquist array method, a frequency-response technique based on inverse transfer-function matrices, is preferred for the design of multivariable controllers for nuclear power plants. This method may be supplemented by information obtained from a modal analysis of the plant model. (auth)

  12. New knowledge network evaluation method for design rationale management

    Science.gov (United States)

    Jing, Shikai; Zhan, Hongfei; Liu, Jihong; Wang, Kuan; Jiang, Hao; Zhou, Jingtao

    2015-01-01

    Current design rationale (DR) systems have not demonstrated the value of the approach in practice since little attention is put to the evaluation method of DR knowledge. To systematize knowledge management process for future computer-aided DR applications, a prerequisite is to provide the measure for the DR knowledge. In this paper, a new knowledge network evaluation method for DR management is presented. The method characterizes the DR knowledge value from four perspectives, namely, the design rationale structure scale, association knowledge and reasoning ability, degree of design justification support and degree of knowledge representation conciseness. The DR knowledge comprehensive value is also measured by the proposed method. To validate the proposed method, different style of DR knowledge network and the performance of the proposed measure are discussed. The evaluation method has been applied in two realistic design cases and compared with the structural measures. The research proposes the DR knowledge evaluation method which can provide object metric and selection basis for the DR knowledge reuse during the product design process. In addition, the method is proved to be more effective guidance and support for the application and management of DR knowledge.

  13. A concept for a usability focused design method

    NARCIS (Netherlands)

    Hoolhorst, F.W.B.; van der Voort, Mascha C.

    2009-01-01

    Many user-centered design methods (UCDM) have been developed within the last decades. However, industry increasingly demands for a new-generation UCDM since only few of the existing UCDM seem to be applicable to the daily design practice. This paper first discusses the main criteria regarding such

  14. The Sources and Methods of Engineering Design Requirement

    DEFF Research Database (Denmark)

    Li, Xuemeng; Zhang, Zhinan; Ahmed-Kristensen, Saeema

    2014-01-01

    to be defined in a new context. This paper focuses on understanding the design requirement sources at the requirement elicitation phase. It aims at proposing an improved design requirement source classification considering emerging markets and presenting current methods for eliciting requirement for each source...

  15. Methods and systems for identifying ligand-protein binding sites

    KAUST Repository

    Gao, Xin

    2016-05-06

    The invention provides a novel integrated structure and system-based approach for drug target prediction that enables the large-scale discovery of new targets for existing drugs Novel computer-readable storage media and computer systems are also provided. Methods and systems of the invention use novel sequence order-independent structure alignment, hierarchical clustering, and probabilistic sequence similarity techniques to construct a probabilistic pocket ensemble (PPE) that captures even promiscuous structural features of different binding sites for a drug on known targets. The drug\\'s PPE is combined with an approximation of the drug delivery profile to facilitate large-scale prediction of novel drug- protein interactions with several applications to biological research and drug development.

  16. Linking proteins to signaling pathways for experiment design and evaluation.

    Directory of Open Access Journals (Sweden)

    Illés J Farkas

    Full Text Available Biomedical experimental work often focuses on altering the functions of selected proteins. These changes can hit signaling pathways, and can therefore unexpectedly and non-specifically affect cellular processes. We propose PathwayLinker, an online tool that can provide a first estimate of the possible signaling effects of such changes, e.g., drug or microRNA treatments. PathwayLinker minimizes the users' efforts by integrating protein-protein interaction and signaling pathway data from several sources with statistical significance tests and clear visualization. We demonstrate through three case studies that the developed tool can point out unexpected signaling bias in normal laboratory experiments and identify likely novel signaling proteins among the interactors of known drug targets. In our first case study we show that knockdown of the Caenorhabditis elegans gene cdc-25.1 (meant to avoid progeny may globally affect the signaling system and unexpectedly bias experiments. In the second case study we evaluate the loss-of-function phenotypes of a less known C. elegans gene to predict its function. In the third case study we analyze GJA1, an anti-cancer drug target protein in human, and predict for this protein novel signaling pathway memberships, which may be sources of side effects. Compared to similar services, a major advantage of PathwayLinker is that it drastically reduces the necessary amount of manual literature searches and can be used without a computational background. PathwayLinker is available at http://PathwayLinker.org. Detailed documentation and source code are available at the website.

  17. CEPIAH, a method for Evaluation and Design of Pedagogical Hypermedia

    OpenAIRE

    Trigano , Philippe; Pacurar Giacomini , Ecaterina

    2004-01-01

    We are working on a method, called CEPIAH. We propose a web based system used to help teachers to design multimedia documents and to evaluate their prototypes. Our tool integrates two modules such as EMPI (Evaluation of Multimedia Pedagogical and Interactive software), and SP/UL/FC, a method for designing pedagogical hypermedia. The EMPI module is used to evaluate multimedia software used in educational context. We structured a knowledge base composed of a list of evaluation criteria, grouped...

  18. The Innovative Bike Conceptual Design by Using Modified Functional Element Design Method

    Directory of Open Access Journals (Sweden)

    Nien-Te Liu

    2016-11-01

    Full Text Available The purpose of the study is to propose a new design process by modifying functional element design approach which can commence a large amount of innovative concepts within a short period of time. Firstly, the original creative functional elements design method is analyzed and the drawbacks are discussed. Then, the modified is proposed and is divided into 6 steps. The creative functional element representations, generalization, specialization, and particularization are used in this method. Every step is described clearly, and users could design by following the process easily. In this paper, a clear and accurate design process is proposed based on the creative functional element design method. By following this method, a lot of innovative bicycles will be created quickly.

  19. A highly sensitive method for detection of molybdenum-containing proteins

    International Nuclear Information System (INIS)

    Kalakutskii, K.L.; Shvetsov, A.A.; Bursakov, S.A.; Letarov, A.V.; Zabolotnyi, A.I.; L'vov, N.P.

    1992-01-01

    A highly sensitive method for detection of molybdenum-containing proteins in gels after electrophoresis has been developed. The method involves in vitro labeling of the proteins with the radioactive isotope 185 W. The method used to detect molybdenum-accumulating proteins in lupine seeds, xanthine dehydrogenase and another molybdenum-containing protein in wheat, barley, and pea seedlings, and nitrate reductase and xanthine dehydrogenase in bacteroides from lupine nodules. Nitrogenase could not be detected by the method. 16 refs., 5 figs

  20. Study on design method for seismically isolated FBR plants

    International Nuclear Information System (INIS)

    Hirata, Kazuta; Yabana, Shuichi; Ohtori, Yasuki; Ishida, Katsuhiko; Sawada, Yoshihiro; Shiojiri; Hiroo; Mazda, Taiji

    1998-01-01

    CRIEPI conducted 'Demonstration test on FBR seismic isolation system' from 1987 to 1996 under contract with Ministry of International Trade and Industry, Japan. In the demonstration test, base isolation technologies are prepared and demonstrated to apply to FBR and the design guidelines are proposed. In this report overall contents of the design guidelines entitled Design guidelines for seismically base isolated FBR plants' are included. The design guidelines, as a rule, are limited to apply to FBR plants where entire reactor building is isolated in the horizontal direction using laminated rubber bearings as isolators. The design guidelines and its concepts, however, will be useful for the development of similar guidelines for other isolation systems using different type of isolation methods and other nuclear facilities. The design guidelines consist of three parts and appendices. The first part is 'Policy for Safety Design of Base Isolated FBR Plants' specifying the principles and the requirements in the planning and the design for the safety of base isolated FBR plants. The second part is Policy for Seismic Design of Base Isolated FBR' describing the principles and the requirements in the seismic design and the evaluation of safety for base isolated FBR plants. The third part is 'Design Methods for Seismic Isolated FBR Plants' detailing the methods, procedures and parameters to be used in the design and the evaluation of safety fro base isolated FBR plants. In appendices examples of design procedures for base isolated reactor building and laminated rubber bearings as well as various test data on laminated rubber bearings, etc. are shown. (author)

  1. A Versatile Method of Patterning Proteins and Cells.

    Science.gov (United States)

    Shrirao, Anil B; Kung, Frank H; Yip, Derek; Firestein, Bonnie L; Cho, Cheul H; Townes-Anderson, Ellen

    2017-02-26

    Substrate and cell patterning techniques are widely used in cell biology to study cell-to-cell and cell-to-substrate interactions. Conventional patterning techniques work well only with simple shapes, small areas and selected bio-materials. This article describes a method to distribute cell suspensions as well as substrate solutions into complex, long, closed (dead-end) polydimethylsiloxane (PDMS) microchannels using negative pressure. This method enables researchers to pattern multiple substrates including fibronectin, collagen, antibodies (Sal-1), poly-D-lysine (PDL), and laminin. Patterning of substrates allows one to indirectly pattern a variety of cells. We have tested C2C12 myoblasts, the PC12 neuronal cell line, embryonic rat cortical neurons, and amphibian retinal neurons. In addition, we demonstrate that this technique can directly pattern fibroblasts in microfluidic channels via brief application of a low vacuum on cell suspensions. The low vacuum does not significantly decrease cell viability as shown by cell viability assays. Modifications are discussed for application of the method to different cell and substrate types. This technique allows researchers to pattern cells and proteins in specific patterns without the need for exotic materials or equipment and can be done in any laboratory with a vacuum.

  2. Integrated airfoil and blade design method for large wind turbines

    DEFF Research Database (Denmark)

    Zhu, Wei Jun; Shen, Wen Zhong; Sørensen, Jens Nørkær

    2014-01-01

    This paper presents an integrated method for designing airfoil families of large wind turbine blades. For a given rotor diameter and a tip speed ratio, optimal airfoils are designed based on the local speed ratios. To achieve a high power performance at low cost, the airfoils are designed...... with the objectives of high Cp and small chord length. When the airfoils are obtained, the optimum flow angle and rotor solidity are calculated which forms the basic input to the blade design. The new airfoils are designed based on a previous in-house designed airfoil family which was optimized at a Reynolds number...... of 3 million. A novel shape perturbation function is introduced to optimize the geometry based on the existing airfoils which simplifies the design procedure. The viscous/inviscid interactive code XFOIL is used as the aerodynamic tool for airfoil optimization at a Reynolds number of 16 million...

  3. CCBuilder: an interactive web-based tool for building, designing and assessing coiled-coil protein assemblies.

    Science.gov (United States)

    Wood, Christopher W; Bruning, Marc; Ibarra, Amaurys Á; Bartlett, Gail J; Thomson, Andrew R; Sessions, Richard B; Brady, R Leo; Woolfson, Derek N

    2014-11-01

    The ability to accurately model protein structures at the atomistic level underpins efforts to understand protein folding, to engineer natural proteins predictably and to design proteins de novo. Homology-based methods are well established and produce impressive results. However, these are limited to structures presented by and resolved for natural proteins. Addressing this problem more widely and deriving truly ab initio models requires mathematical descriptions for protein folds; the means to decorate these with natural, engineered or de novo sequences; and methods to score the resulting models. We present CCBuilder, a web-based application that tackles the problem for a defined but large class of protein structure, the α-helical coiled coils. CCBuilder generates coiled-coil backbones, builds side chains onto these frameworks and provides a range of metrics to measure the quality of the models. Its straightforward graphical user interface provides broad functionality that allows users to build and assess models, in which helix geometry, coiled-coil architecture and topology and protein sequence can be varied rapidly. We demonstrate the utility of CCBuilder by assembling models for 653 coiled-coil structures from the PDB, which cover >96% of the known coiled-coil types, and by generating models for rarer and de novo coiled-coil structures. CCBuilder is freely available, without registration, at http://coiledcoils.chm.bris.ac.uk/app/cc_builder/. © The Author 2014. Published by Oxford University Press.

  4. Modular design strategies for protein sensors and switches

    NARCIS (Netherlands)

    Merkx, M.; Ryadnov, M.; Brunsveld, L.; Suga, H.

    2014-01-01

    Protein-based sensors and switches provide attractive tools for the real-time monitoring and control of molecular processes in complex biological environments, with applications ranging from intracellular imaging to the rewiring of signal transduction pathways and molecular diagnostics. A

  5. Rational design of FRET-based sensor proteins

    NARCIS (Netherlands)

    Merkx, M.

    2008-01-01

    Real-time imaging of molecular events inside living cells is important for understanding the basis of physiological processes and diseases. Genetically encoded sensors that use fluorescence resonance energy transfer (FRET) between two fluorescent proteins are attractive in this respect because they

  6. High-throughput method for optimum solubility screening for homogeneity and crystallization of proteins

    Science.gov (United States)

    Kim, Sung-Hou [Moraga, CA; Kim, Rosalind [Moraga, CA; Jancarik, Jamila [Walnut Creek, CA

    2012-01-31

    An optimum solubility screen in which a panel of buffers and many additives are provided in order to obtain the most homogeneous and monodisperse protein condition for protein crystallization. The present methods are useful for proteins that aggregate and cannot be concentrated prior to setting up crystallization screens. A high-throughput method using the hanging-drop method and vapor diffusion equilibrium and a panel of twenty-four buffers is further provided. Using the present methods, 14 poorly behaving proteins have been screened, resulting in 11 of the proteins having highly improved dynamic light scattering results allowing concentration of the proteins, and 9 were crystallized.

  7. Generic methods for design of small-bore pipe supports

    International Nuclear Information System (INIS)

    Clark, G.L.; LaSalle, F.R.

    1981-01-01

    Large numbers of supports for small-bore, low-temperature pipe are utilized in nuclear power plants. These supports often must meet ASME code and project seismic design requirements. Detailed analysis for each support is time consuming and costly. This paper describes some economical generic methods developed to design and qualify supports for two-inch and smaller pipe operating at temperatures less than 300 0 F (185 0 C), on the Fast Flux Test Facility. Use of standard designs, standard support spacing tables, anchor bolt and baseplate considerations, and field qualification methods are discussed

  8. IDEF method for designing seismic information system in CTBT verification

    International Nuclear Information System (INIS)

    Zheng Xuefeng; Shen Junyi; Jin Ping; Zhang Huimin; Zheng Jiangling; Sun Peng

    2004-01-01

    Seismic information system is of great importance for improving the capability of CTBT verification. A large amount of money has been appropriated for the research in this field in the U.S. and some other countries in recent years. However, designing and developing a seismic information system involves various technologies about complex system design. This paper discusses the IDEF0 method to construct function models and the IDEF1x method to make information models systemically, as well as how they are used in designing seismic information system in CTBT verification. (authors)

  9. Urban and Building Design Methods for Resource Management

    DEFF Research Database (Denmark)

    Sattrup, Peter Andreas

    2014-01-01

    . Having a structured approach to design methods, a design methodology, is a fundamental aid in decisionmaking and resource management through design. At DTU Civil Engineering experiments are made in crossdisciplinary collaboration between engineers of different specializations and outside collaborators...... but a fewdimensions. Engineers may influence decision making at all levels, and do in many instances have directresponsibility for decision making, - however many (Civil) engineers don’t really think of themselves asdesigners. However this perception is changing. Engineering is fundamentally a design discipline...... management and decision support regardingthe development of the built environment towards a sustainable future....

  10. First principles design of a core bioenergetic transmembrane electron-transfer protein

    Energy Technology Data Exchange (ETDEWEB)

    Goparaju, Geetha; Fry, Bryan A.; Chobot, Sarah E.; Wiedman, Gregory; Moser, Christopher C.; Leslie Dutton, P.; Discher, Bohdana M.

    2016-05-01

    Here we describe the design, Escherichia coli expression and characterization of a simplified, adaptable and functionally transparent single chain 4-α-helix transmembrane protein frame that binds multiple heme and light activatable porphyrins. Such man-made cofactor-binding oxidoreductases, designed from first principles with minimal reference to natural protein sequences, are known as maquettes. This design is an adaptable frame aiming to uncover core engineering principles governing bioenergetic transmembrane electron-transfer function and recapitulate protein archetypes proposed to represent the origins of photosynthesis. This article is part of a Special Issue entitled Biodesign for Bioenergetics — the design and engineering of electronic transfer cofactors, proteins and protein networks, edited by Ronald L. Koder and J.L. Ross Anderson.

  11. Designing waveforms for temporal encoding using a frequency sampling method

    DEFF Research Database (Denmark)

    Gran, Fredrik; Jensen, Jørgen Arendt

    2007-01-01

    was compared to a linear frequency modulated signal with amplitude tapering, previously used in clinical studies for synthetic transmit aperture imaging. The latter had a relatively flat spectrum which implied that the waveform tried to excite all frequencies including ones with low amplification. The proposed......In this paper a method for designing waveforms for temporal encoding in medical ultrasound imaging is described. The method is based on least squares optimization and is used to design nonlinear frequency modulated signals for synthetic transmit aperture imaging. By using the proposed design method...... waveform, on the other hand, was designed so that only frequencies where the transducer had a large amplification were excited. Hereby, unnecessary heating of the transducer could be avoided and the signal-tonoise ratio could be increased. The experimental ultrasound scanner RASMUS was used to evaluate...

  12. Fuel cell design using a new heuristic method

    International Nuclear Information System (INIS)

    Perusquia, R.; Montes T, J. L.; Ortiz S, J. J.; Castillo M, A.

    2014-10-01

    In this paper a new method for the pre-design of a typical fuel cell with a structural array of 10 x 10 fuel elements for a BWR is presented. The method is based on principles of maximum dispersion and minimum peaks of local power within the array of fuel elements. The pre-design of the fuel cells is made by simulation in two dimensions (2-D) through the cells physics code CASMO-4. For this purpose of pre-design the search process is guided by an objective function which is a combination of the main neutronic parameters of the fuel cell. The results show that the method is a promising tool that could be used for the design of fuel cells for use in a nuclear plant BWR. (Author)

  13. A rapid method for soil cement design : Louisiana slope value method.

    Science.gov (United States)

    1964-03-01

    The current procedure used by the Louisiana Department of Highways for laboratory design of cement stabilized soil base and subbase courses is taken from standard AASHO test methods, patterned after Portland Cement Association criteria. These methods...

  14. Designing, Teaching, and Evaluating Two Complementary Mixed Methods Research Courses

    Science.gov (United States)

    Christ, Thomas W.

    2009-01-01

    Teaching mixed methods research is difficult. This longitudinal explanatory study examined how two classes were designed, taught, and evaluated. Curriculum, Research, and Teaching (EDCS-606) and Mixed Methods Research (EDCS-780) used a research proposal generation process to highlight the importance of the purpose, research question and…

  15. The co-constructing stories method : feedback of designers on use of the method in real design cases

    NARCIS (Netherlands)

    Buskermolen, D.; Terken, J.M.B.; Eggen, J.H.

    2015-01-01

    In this paper we present the "Co-constructing Stories" method, aiming to elicit feedback from end-users on novel design concepts in the early phases of the design process. In sessions of less than an hour, participants are prompted by a storyboard depicting the current situation to recollect

  16. A de novo designed monomeric, compact three helix bundle protein on a carbohydrate template

    DEFF Research Database (Denmark)

    Malik, Leila; Nygård, Jesper; Christensen, Niels Johan

    2015-01-01

    De novo design and chemical synthesis of proteins and of other artificial structures, which mimic them, is a central strategy for understanding protein folding and for accessing proteins with novel functions. We have previously described carbohydrates as templates for the assembly of artificial...... the template could facilitate protein folding. Here we report the design and synthesis of 3-helix bundle carboproteins on deoxy-hexopyranosides. The carboproteins were analyzed by CD, AUC, SAXS, and NMR, which revealed the formation of the first compact, and folded monomeric carboprotein distinctly different...

  17. Towards a culturally independent participatory design method: Fusing game elements into the design process

    DEFF Research Database (Denmark)

    Jensen, Mika Yasuoka; Nakatani, Momoko; Ohno, Takehiko

    2013-01-01

    Historically, Participatory Design (PD) was introduced and applied in the Scandinavian and American context as a practical design method for collective creativity and stakeholder involvement. In this paper, by fusing game elements into PD, we suggest a first step towards a culturally independent ...... imply that the introduction of game elements allows PD to be effectively utilized in culturally diverse settings.......Historically, Participatory Design (PD) was introduced and applied in the Scandinavian and American context as a practical design method for collective creativity and stakeholder involvement. In this paper, by fusing game elements into PD, we suggest a first step towards a culturally independent PD...... method called the ICT Service Design Game to ease the prevailing concern that PD has limited applicability in other cultural settings. We conduct four experiments on ICT Service Design Game in Scandinavia and Asia to evaluate its feasibility. The experiments identify some differences in the PD process...

  18. Endurance time method for Seismic analysis and design of structures

    International Nuclear Information System (INIS)

    Estekanchi, H.E.; Vafai, A.; Sadeghazar, M.

    2004-01-01

    In this paper, a new method for performance based earthquake analysis and design has been introduced. In this method, the structure is subjected to accelerograms that impose increasing dynamic demand on the structure with time. Specified damage indexes are monitored up to the collapse level or other performance limit that defines the endurance limit point for the structure. Also, a method for generating standard intensifying accelerograms has been described. Three accelerograms have been generated using this method. Furthermore, the concept of Endurance Time has been described by applying these accelerograms to single and multi degree of freedom linear systems. The application of this method for analysis of complex nonlinear systems has been explained. Endurance Time method provides a uniform approach to seismic analysis and design of complex structures that can be applied in numerical and experimental investigations

  19. Integrated airfoil and blade design method for large wind turbines

    DEFF Research Database (Denmark)

    Zhu, Wei Jun; Shen, Wen Zhong

    2013-01-01

    This paper presents an integrated method for designing airfoil families of large wind turbine blades. For a given rotor diameter and tip speed ratio, the optimal airfoils are designed based on the local speed ratios. To achieve high power performance at low cost, the airfoils are designed...... with an objective of high Cp and small chord length. When the airfoils are obtained, the optimum flow angle and rotor solidity are calculated which forms the basic input to the blade design. The new airfoils are designed based on the previous in-house airfoil family which were optimized at a Reynolds number of 3...... million. A novel shape perturbation function is introduced to optimize the geometry on the existing airfoils and thus simplify the design procedure. The viscos/inviscid code Xfoil is used as the aerodynamic tool for airfoil optimization where the Reynolds number is set at 16 million with a free...

  20. Design and characterization of protein-quercetin bioactive nanoparticles

    Directory of Open Access Journals (Sweden)

    Leng Xiaojing

    2011-05-01

    Full Text Available Abstract Background The synthesis of bioactive nanoparticles with precise molecular level control is a major challenge in bionanotechnology. Understanding the nature of the interactions between the active components and transport biomaterials is thus essential for the rational formulation of bio-nanocarriers. The current study presents a single molecule of bovine serum albumin (BSA, lysozyme (Lys, or myoglobin (Mb used to load hydrophobic drugs such as quercetin (Q and other flavonoids. Results Induced by dimethyl sulfoxide (DMSO, BSA, Lys, and Mb formed spherical nanocarriers with sizes less than 70 nm. After loading Q, the size was further reduced by 30%. The adsorption of Q on protein is mainly hydrophobic, and is related to the synergy of Trp residues with the molecular environment of the proteins. Seven Q molecules could be entrapped by one Lys molecule, 9 by one Mb, and 11 by one BSA. The controlled releasing measurements indicate that these bioactive nanoparticles have long-term antioxidant protection effects on the activity of Q in both acidic and neutral conditions. The antioxidant activity evaluation indicates that the activity of Q is not hindered by the formation of protein nanoparticles. Other flavonoids, such as kaempferol and rutin, were also investigated. Conclusions BSA exhibits the most remarkable abilities of loading, controlled release, and antioxidant protection of active drugs, indicating that such type of bionanoparticles is very promising in the field of bionanotechnology.

  1. Rapid method for protein quantitation by Bradford assay after elimination of the interference of polysorbate 80.

    Science.gov (United States)

    Cheng, Yongfeng; Wei, Haiming; Sun, Rui; Tian, Zhigang; Zheng, Xiaodong

    2016-02-01

    Bradford assay is one of the most common methods for measuring protein concentrations. However, some pharmaceutical excipients, such as detergents, interfere with Bradford assay even at low concentrations. Protein precipitation can be used to overcome sample incompatibility with protein quantitation. But the rate of protein recovery caused by acetone precipitation is only about 70%. In this study, we found that sucrose not only could increase the rate of protein recovery after 1 h acetone precipitation, but also did not interfere with Bradford assay. So we developed a method for rapid protein quantitation in protein drugs even if they contained interfering substances. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. SSFI and SSOMI new method of evaluating design

    International Nuclear Information System (INIS)

    Tolson, G.M.

    1992-01-01

    The NRC has developed a new inspection method which has proven its effectiveness in evaluating design organizations. The new method is used in two types of NRC inspections, Safety System Functional Inspection (SSFI), and Safety System Outage Modification Inspection (SSOMI). The SSFI/SSOMI audits were developed following an event which brought a nuclear power plant close to a core meltdown. That event was caused by a series of problems which would not have been found using conventional methods. The SSFI and SSOMI audits involve intense technical evaluation of a nuclear system to determine wheter the system will function as designed. The SSFI/SSOMI method normally uses eight to fifteen engineers with different fields of expertise to evaluate a system, or a change to a system in the case of a SSOMI. The effectiveness of each engineer's input is amplified in a series of open, questioning, free-wheeling, brainstorming-type team meetings. During the team meetings, all aspects of the audit are controlled by a consensus of the team members. The findings from these new methods are surprisingly consistent, regardless of which organization is audited or which organization performs the audit. This consistency implies a widespread generic weakness in the manner design is being performed. This paper addresses generic findings and recommends increased use of these new methods to evaluate design organizations. These audit methods can be readily used to evaluate any process or system. (orig.)

  3. Advances in product family and product platform design methods & applications

    CERN Document Server

    Jiao, Jianxin; Siddique, Zahed; Hölttä-Otto, Katja

    2014-01-01

    Advances in Product Family and Product Platform Design: Methods & Applications highlights recent advances that have been made to support product family and product platform design and successful applications in industry. This book provides not only motivation for product family and product platform design—the “why” and “when” of platforming—but also methods and tools to support the design and development of families of products based on shared platforms—the “what”, “how”, and “where” of platforming. It begins with an overview of recent product family design research to introduce readers to the breadth of the topic and progresses to more detailed topics and design theory to help designers, engineers, and project managers plan, architect, and implement platform-based product development strategies in their companies. This book also: Presents state-of-the-art methods and tools for product family and product platform design Adopts an integrated, systems view on product family and pro...

  4. 77 FR 32632 - Ambient Air Monitoring Reference and Equivalent Methods: Designation of Three New Equivalent Methods

    Science.gov (United States)

    2012-06-01

    ... Methods: Designation of Three New Equivalent Methods AGENCY: Environmental Protection Agency. ACTION... accordance with 40 CFR Part 53, three new equivalent methods: One for measuring concentrations of nitrogen... INFORMATION: In accordance with regulations at 40 CFR Part 53, the EPA evaluates various methods for...

  5. Transferable coarse-grained potential for de novo protein folding and design.

    Directory of Open Access Journals (Sweden)

    Ivan Coluzza

    Full Text Available Protein folding and design are major biophysical problems, the solution of which would lead to important applications especially in medicine. Here we provide evidence of how a novel parametrization of the Caterpillar model may be used for both quantitative protein design and folding. With computer simulations it is shown that, for a large set of real protein structures, the model produces designed sequences with similar physical properties to the corresponding natural occurring sequences. The designed sequences require further experimental testing. For an independent set of proteins, previously used as benchmark, the correct folded structure of both the designed and the natural sequences is also demonstrated. The equilibrium folding properties are characterized by free energy calculations. The resulting free energy profiles not only are consistent among natural and designed proteins, but also show a remarkable precision when the folded structures are compared to the experimentally determined ones. Ultimately, the updated Caterpillar model is unique in the combination of its fundamental three features: its simplicity, its ability to produce natural foldable designed sequences, and its structure prediction precision. It is also remarkable that low frustration sequences can be obtained with such a simple and universal design procedure, and that the folding of natural proteins shows funnelled free energy landscapes without the need of any potentials based on the native structure.

  6. Engineering nutritious proteins: improvement of stability in the designer protein MB-1 via introduction of disulfide bridges.

    Science.gov (United States)

    Doucet, Alain; Williams, Martin; Gagnon, Mylene C; Sasseville, Maxime; Beauregard, Marc

    2002-01-02

    Protein design is currently used for the creation of new proteins with desirable traits. In this laboratory the focus has been on the synthesis of proteins with high essential amino acid content having potential applications in animal nutrition. One of the limitations faced in this endeavor is achieving stable proteins despite a highly biased amino acid content. Reported here are the synthesis and characterization of two disulfide-bridged mutants derived from the MB-1 designer protein. Both mutants outperformed their parent protein MB-1 with their bridge formed, as shown by circular dichroism, size exclusion chromatography, thermal denaturation, and proteolytic degradation experiments. When the disulfide bridges were cleaved, the mutants' behavior changed: the mutants significantly unfolded, suggesting that the introduction of Cys residues was deleterious to MB-1-folding. In an attempt to compensate for the mutations used, a Tyr62-Trp mutation was performed, leading to an increase in bulk and hydrophobicity in the core. The Trp-containing disulfide-bridged mutants did not behave as well as the original MB-1Trp, suggesting that position 62 might not be adequate for a compensatory mutation.

  7. Optimal protein library design using recombination or point mutations based on sequence-based scoring functions.

    Science.gov (United States)

    Pantazes, Robert J; Saraf, Manish C; Maranas, Costas D

    2007-08-01

    In this paper, we introduce and test two new sequence-based protein scoring systems (i.e. S1, S2) for assessing the likelihood that a given protein hybrid will be functional. By binning together amino acids with similar properties (i.e. volume, hydrophobicity and charge) the scoring systems S1 and S2 allow for the quantification of the severity of mismatched interactions in the hybrids. The S2 scoring system is found to be able to significantly functionally enrich a cytochrome P450 library over other scoring methods. Given this scoring base, we subsequently constructed two separate optimization formulations (i.e. OPTCOMB and OPTOLIGO) for optimally designing protein combinatorial libraries involving recombination or mutations, respectively. Notably, two separate versions of OPTCOMB are generated (i.e. model M1, M2) with the latter allowing for position-dependent parental fragment skipping. Computational benchmarking results demonstrate the efficacy of models OPTCOMB and OPTOLIGO to generate high scoring libraries of a prespecified size.

  8. Gene composer: database software for protein construct design, codon engineering, and gene synthesis.

    Science.gov (United States)

    Lorimer, Don; Raymond, Amy; Walchli, John; Mixon, Mark; Barrow, Adrienne; Wallace, Ellen; Grice, Rena; Burgin, Alex; Stewart, Lance

    2009-04-21

    To improve efficiency in high throughput protein structure determination, we have developed a database software package, Gene Composer, which facilitates the information-rich design of protein constructs and their codon engineered synthetic gene sequences. With its modular workflow design and numerous graphical user interfaces, Gene Composer enables researchers to perform all common bio-informatics steps used in modern structure guided protein engineering and synthetic gene engineering. An interactive Alignment Viewer allows the researcher to simultaneously visualize sequence conservation in the context of known protein secondary structure, ligand contacts, water contacts, crystal contacts, B-factors, solvent accessible area, residue property type and several other useful property views. The Construct Design Module enables the facile design of novel protein constructs with altered N- and C-termini, internal insertions or deletions, point mutations, and desired affinity tags. The modifications can be combined and permuted into multiple protein constructs, and then virtually cloned in silico into defined expression vectors. The Gene Design Module uses a protein-to-gene algorithm that automates the back-translation of a protein amino acid sequence into a codon engineered nucleic acid gene sequence according to a selected codon usage table with minimal codon usage threshold, defined G:C% content, and desired sequence features achieved through synonymous codon selection that is optimized for the intended expression system. The gene-to-oligo algorithm of the Gene Design Module plans out all of the required overlapping oligonucleotides and mutagenic primers needed to synthesize the desired gene constructs by PCR, and for physically cloning them into selected vectors by the most popular subcloning strategies. We present a complete description of Gene Composer functionality, and an efficient PCR-based synthetic gene assembly procedure with mis-match specific endonuclease

  9. Gene Composer: database software for protein construct design, codon engineering, and gene synthesis

    Directory of Open Access Journals (Sweden)

    Mixon Mark

    2009-04-01

    Full Text Available Abstract Background To improve efficiency in high throughput protein structure determination, we have developed a database software package, Gene Composer, which facilitates the information-rich design of protein constructs and their codon engineered synthetic gene sequences. With its modular workflow design and numerous graphical user interfaces, Gene Composer enables researchers to perform all common bio-informatics steps used in modern structure guided protein engineering and synthetic gene engineering. Results An interactive Alignment Viewer allows the researcher to simultaneously visualize sequence conservation in the context of known protein secondary structure, ligand contacts, water contacts, crystal contacts, B-factors, solvent accessible area, residue property type and several other useful property views. The Construct Design Module enables the facile design of novel protein constructs with altered N- and C-termini, internal insertions or deletions, point mutations, and desired affinity tags. The modifications can be combined and permuted into multiple protein constructs, and then virtually cloned in silico into defined expression vectors. The Gene Design Module uses a protein-to-gene algorithm that automates the back-translation of a protein amino acid sequence into a codon engineered nucleic acid gene sequence according to a selected codon usage table with minimal codon usage threshold, defined G:C% content, and desired sequence features achieved through synonymous codon selection that is optimized for the intended expression system. The gene-to-oligo algorithm of the Gene Design Module plans out all of the required overlapping oligonucleotides and mutagenic primers needed to synthesize the desired gene constructs by PCR, and for physically cloning them into selected vectors by the most popular subcloning strategies. Conclusion We present a complete description of Gene Composer functionality, and an efficient PCR-based synthetic gene

  10. Methods for air cleaning system design and accident analysis

    International Nuclear Information System (INIS)

    Gregory, W.S.; Nichols, B.D.

    1987-01-01

    This paper describes methods, in the form of a handbook and five computer codes, that can be used for nuclear facility air cleaning system design and accident analysis. Four of the codes were developed primarily at the Los Alamos National Laboratory, and one was developed in France. Tools such as these are used to design ventilation systems in the mining industry but do not seem to be commonly used in the nuclear industry. For example, the Nuclear Air Cleaning Handbook is an excellent design reference, but it fails to include information on computer codes that can be used to aid in the design process. These computer codes allow the analyst to use the handbook information to form all the elements of a complete system design. Because these analysis methods are in the form of computer codes they allow the analyst to investigate many alternative designs. In addition, the effects of many accident scenarios on the operation of the air cleaning system can be evaluated. These tools originally were intended for accident analysis, but they have been used mostly as design tools by several architect-engineering firms. The Cray, VAX, and personal computer versions of the codes, an accident analysis handbook, and the codes availability will be discussed. The application of these codes to several design operations of nuclear facilities will be illustrated, and their use to analyze the effect of several accident scenarios also will be described

  11. Adaptive design methods in clinical trials – a review

    Directory of Open Access Journals (Sweden)

    Chang Mark

    2008-05-01

    Full Text Available Abstract In recent years, the use of adaptive design methods in clinical research and development based on accrued data has become very popular due to its flexibility and efficiency. Based on adaptations applied, adaptive designs can be classified into three categories: prospective, concurrent (ad hoc, and retrospective adaptive designs. An adaptive design allows modifications made to trial and/or statistical procedures of ongoing clinical trials. However, it is a concern that the actual patient population after the adaptations could deviate from the originally target patient population and consequently the overall type I error (to erroneously claim efficacy for an infective drug rate may not be controlled. In addition, major adaptations of trial and/or statistical procedures of on-going trials may result in a totally different trial that is unable to address the scientific/medical questions the trial intends to answer. In this article, several commonly considered adaptive designs in clinical trials are reviewed. Impacts of ad hoc adaptations (protocol amendments, challenges in by design (prospective adaptations, and obstacles of retrospective adaptations are described. Strategies for the use of adaptive design in clinical development of rare diseases are discussed. Some examples concerning the development of Velcade intended for multiple myeloma and non-Hodgkin's lymphoma are given. Practical issues that are commonly encountered when implementing adaptive design methods in clinical trials are also discussed.

  12. Renewing Theories, Methods and Design Practices: Challenges for Architectural Education

    Directory of Open Access Journals (Sweden)

    Andri Yatmo Yandi

    2018-01-01

    Full Text Available Architectural education should promote the advancement of knowledge that is necessary as the basis for the development of excellent design practice. Architectural education needs to respond appropriately to the current issues in the society. To find its way into the society in an appropriate way, architecture needs to be liquid. The ability to address the liquidity of architecture requires educational approach that promotes the ability to work with a range of design methods and approaches. There are several principles that become the basis for developing architectural education that could strengthen its position within the society: to promote knowledge-based design practice, to embrace variety of design methods and approaches; to keep a balance between design knowledge and design skills; while at the same time to aim for mastery and excellence in design. These principles should be the basis for defining and developing the curriculum and the process of design learning architectural education. Then the main challenge is on our willingness to be liquid in developing architectural education, which needs continuous renewal and update to respond to the changing context of knowledge, technology and society.

  13. Making Design Decisions Visible: Applying the Case-Based Method in Designing Online Instruction

    Directory of Open Access Journals (Sweden)

    Heng Luo,

    2011-01-01

    Full Text Available The instructional intervention in this design case is a self-directed online tutorial that applies the case-based method to teach educators how to design and conduct entrepreneurship programs for elementary school students. In this article, the authors describe the major decisions made in each phase of the design and development process, explicate the rationales behind them, and demonstrate their effect on the production of the tutorial. Based on such analysis, the guidelines for designing case-based online instruction are summarized for the design case.

  14. A design method for process design kit based on an SMIC 65 nm process

    International Nuclear Information System (INIS)

    Luo Haiyan; Chen Lan; Yin Minghui

    2010-01-01

    The frame structure of a process design kit (PDK) is described in detail, and a practical design method for PDK is presented. Based on this method, a useful SMIC 65 nm PDK has been successfully designed and realized, which is applicable to native EDA software of Zeni. The design process and difficulties of PDK are introduced by developing and analyzing these parameterized cell (Pcell) devices (MOS, resistor, etc.). A structured design method was proposed to implement Pcell, which makes thousands upon thousands of source codes of Pcell concise, readable, easy-to-upkeep and transplantable. Moreover, a Pcase library for each Pcell is designed to verify the Pcell in batches. By this approach, the Pcell can be verified efficiently and the PDK will be more reliable and steady. In addition, the component description format parameters and layouts of the Pcell are optimized by adding flexibility and improving performance, which benefits analog and custom IC designers to satisfy the demand of design. Finally, the SMIC 65 nm PDK was applied to IC design. The results indicate that the SMIC 65 nm PDK is competent to support IC design. (semiconductor integrated circuits)

  15. Mixed methods research design for pragmatic psychoanalytic studies.

    Science.gov (United States)

    Tillman, Jane G; Clemence, A Jill; Stevens, Jennifer L

    2011-10-01

    Calls for more rigorous psychoanalytic studies have increased over the past decade. The field has been divided by those who assert that psychoanalysis is properly a hermeneutic endeavor and those who see it as a science. A comparable debate is found in research methodology, where qualitative and quantitative methods have often been seen as occupying orthogonal positions. Recently, Mixed Methods Research (MMR) has emerged as a viable "third community" of research, pursuing a pragmatic approach to research endeavors through integrating qualitative and quantitative procedures in a single study design. Mixed Methods Research designs and the terminology associated with this emerging approach are explained, after which the methodology is explored as a potential integrative approach to a psychoanalytic human science. Both qualitative and quantitative research methods are reviewed, as well as how they may be used in Mixed Methods Research to study complex human phenomena.

  16. Learning to Design Together: Introducing Conditional Design as a Method for Co-design Activities

    DEFF Research Database (Denmark)

    Akoglu, Canan

    2017-01-01

    In today’s world, designing include participation of users and stakeholders at different levels varying from minimum participation to co-creating with these actors. In such a context, it becomes crucial to include related educational modules to be able to prepare design students for their future...... as the empirical study of this paper. The participants of the workshops were students from Communication Design and Industrial Design undergraduate programs with different seniorities in the same faculty. In terms of its content and operative flow, all the workshops were organized in a way that would enable equal...... contribution from each student and an active learning space was provided to the students. Based on the feedbacks, it is possible to foresee that the workshops were positive experiences especially in terms of understanding the importance of collective creativity and beyond the educational purposes...

  17. Simultaneous inhibition of aberrant cancer kinome using rationally designed polymer-protein core-shell nanomedicine.

    Science.gov (United States)

    Chandran, Parwathy; Gupta, Neha; Retnakumari, Archana Payickattu; Malarvizhi, Giridharan Loghanathan; Keechilat, Pavithran; Nair, Shantikumar; Koyakutty, Manzoor

    2013-11-01

    Simultaneous inhibition of deregulated cancer kinome using rationally designed nanomedicine is an advanced therapeutic approach. Herein, we have developed a polymer-protein core-shell nanomedicine to inhibit critically aberrant pro-survival kinases (mTOR, MAPK and STAT5) in primitive (CD34(+)/CD38(-)) Acute Myeloid Leukemia (AML) cells. The nanomedicine consists of poly-lactide-co-glycolide core (~250 nm) loaded with mTOR inhibitor, everolimus, and albumin shell (~25 nm thick) loaded with MAPK/STAT5 inhibitor, sorafenib and the whole construct was surface conjugated with monoclonal antibody against CD33 receptor overexpressed in AML. Electron microscopy confirmed formation of core-shell nanostructure (~290 nm) and flow cytometry and confocal studies showed enhanced cellular uptake of targeted nanomedicine. Simultaneous inhibition of critical kinases causing synergistic lethality against leukemic cells, without affecting healthy blood cells, was demonstrated using immunoblotting, cytotoxicity and apoptosis assays. This cell receptor plus multi-kinase targeted core-shell nanomedicine was found better specific and tolerable compared to current clinical regime of cytarabine and daunorubicin. These authors demonstrate simultaneous inhibition of critical kinases causing synergistic lethality against leukemic cells, without affecting healthy blood cells by using rationally designed polymer-protein core-shell nanomedicine, provoding an advanced method to eliminate cancer cells, with the hope of future therapeutic use. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. How to gamify? A method for designing gamification

    OpenAIRE

    Morschheuser, Benedikt; Werder, Karl; Hamari, Juho; Abe, Julian

    2017-01-01

    During recent years, gamification has become a popular method of enriching information technologies. Popular business analysts have made promising predictions about penetration of gamification, however, it has also been estimated that most gamifica-tion efforts will fail due to poor understanding of how gamification should be designed and implemented. Therefore, in this paper we seek to advance the understanding of best practices related to the gamifica-tion design process. We approach this r...

  19. Effect of the sequence data deluge on the performance of methods for detecting protein functional residues.

    Science.gov (United States)

    Garrido-Martín, Diego; Pazos, Florencio

    2018-02-27

    The exponential accumulation of new sequences in public databases is expected to improve the performance of all the approaches for predicting protein structural and functional features. Nevertheless, this was never assessed or quantified for some widely used methodologies, such as those aimed at detecting functional sites and functional subfamilies in protein multiple sequence alignments. Using raw protein sequences as only input, these approaches can detect fully conserved positions, as well as those with a family-dependent conservation pattern. Both types of residues are routinely used as predictors of functional sites and, consequently, understanding how the sequence content of the databases affects them is relevant and timely. In this work we evaluate how the growth and change with time in the content of sequence databases affect five sequence-based approaches for detecting functional sites and subfamilies. We do that by recreating historical versions of the multiple sequence alignments that would have been obtained in the past based on the database contents at different time points, covering a period of 20 years. Applying the methods to these historical alignments allows quantifying the temporal variation in their performance. Our results show that the number of families to which these methods can be applied sharply increases with time, while their ability to detect potentially functional residues remains almost constant. These results are informative for the methods' developers and final users, and may have implications in the design of new sequencing initiatives.

  20. CREATIVITY METHODS IN TEACHING THE ARCH-DESIGN STUDIO

    Directory of Open Access Journals (Sweden)

    EIGBEONAN Andrew B.

    2013-07-01

    Full Text Available The aim of this paper is to search and find methods of fostering creativity or ideas relating to creativity in teaching the arch-design studio. Teaching creativity through its methods will be making the students grounded in designing with creativity ideas and therefore we can have professionals that design and build with satisfaction, safety and complementary. It means we can have real buildings and places that satisfy our clients, the society and in harmony with the environment. Although there are similarities in the curricula of training architects all over the world, but educators go about it in their own convenient and suitable ways and styles. The ideas of creativity have been part of architecture from the onset, but are not deligently applied and also not formally incorporated in the curricula of training. The topic is also very relevant and timely as arch-educators and other stakeholders are of the opinion that something has to be done to improve the ways and methods of training architects, especially the teaching of the arch-design studio with regards to creativity. Through exploration of literature and interviews (physical and telephone call this paper finds methods of stimulating creativity ideas in the teaching of arch-design studio. Some of the methods of motivating creativity found in teaching the arch-design studio are: analogy, metaphors, biomimicry, brainstorming, attribute listing, mental map, TRIZ, restrictions, charrette, browsing, excursions, focus groups, other peoples viewpoints, using crazy ideas, using experts, visualizing a goal, working with dreams and images and giving students design tools such as drawings CAD and model making.

  1. Design of large Francis turbine using optimal methods

    Science.gov (United States)

    Flores, E.; Bornard, L.; Tomas, L.; Liu, J.; Couston, M.

    2012-11-01

    Among a high number of Francis turbine references all over the world, covering the whole market range of heads, Alstom has especially been involved in the development and equipment of the largest power plants in the world : Three Gorges (China -32×767 MW - 61 to 113 m), Itaipu (Brazil- 20x750 MW - 98.7m to 127m) and Xiangjiaba (China - 8x812 MW - 82.5m to 113.6m - in erection). Many new projects are under study to equip new power plants with Francis turbines in order to answer an increasing demand of renewable energy. In this context, Alstom Hydro is carrying out many developments to answer those needs, especially for jumbo units such the planned 1GW type units in China. The turbine design for such units requires specific care by using the state of the art in computation methods and the latest technologies in model testing as well as the maximum feedback from operation of Jumbo plants already in operation. We present in this paper how a large Francis turbine can be designed using specific design methods, including the global and local optimization methods. The design of the spiral case, the tandem cascade profiles, the runner and the draft tube are designed with optimization loops involving a blade design tool, an automatic meshing software and a Navier-Stokes solver, piloted by a genetic algorithm. These automated optimization methods, presented in different papers over the last decade, are nowadays widely used, thanks to the growing computation capacity of the HPC clusters: the intensive use of such optimization methods at the turbine design stage allows to reach very high level of performances, while the hydraulic flow characteristics are carefully studied over the whole water passage to avoid any unexpected hydraulic phenomena.

  2. Design of large Francis turbine using optimal methods

    International Nuclear Information System (INIS)

    Flores, E; Bornard, L; Tomas, L; Couston, M; Liu, J

    2012-01-01

    Among a high number of Francis turbine references all over the world, covering the whole market range of heads, Alstom has especially been involved in the development and equipment of the largest power plants in the world : Three Gorges (China −32×767 MW - 61 to 113 m), Itaipu (Brazil- 20x750 MW - 98.7m to 127m) and Xiangjiaba (China - 8x812 MW - 82.5m to 113.6m - in erection). Many new projects are under study to equip new power plants with Francis turbines in order to answer an increasing demand of renewable energy. In this context, Alstom Hydro is carrying out many developments to answer those needs, especially for jumbo units such the planned 1GW type units in China. The turbine design for such units requires specific care by using the state of the art in computation methods and the latest technologies in model testing as well as the maximum feedback from operation of Jumbo plants already in operation. We present in this paper how a large Francis turbine can be designed using specific design methods, including the global and local optimization methods. The design of the spiral case, the tandem cascade profiles, the runner and the draft tube are designed with optimization loops involving a blade design tool, an automatic meshing software and a Navier-Stokes solver, piloted by a genetic algorithm. These automated optimization methods, presented in different papers over the last decade, are nowadays widely used, thanks to the growing computation capacity of the HPC clusters: the intensive use of such optimization methods at the turbine design stage allows to reach very high level of performances, while the hydraulic flow characteristics are carefully studied over the whole water passage to avoid any unexpected hydraulic phenomena.

  3. Breaking from binaries - using a sequential mixed methods design.

    Science.gov (United States)

    Larkin, Patricia Mary; Begley, Cecily Marion; Devane, Declan

    2014-03-01

    To outline the traditional worldviews of healthcare research and discuss the benefits and challenges of using mixed methods approaches in contributing to the development of nursing and midwifery knowledge. There has been much debate about the contribution of mixed methods research to nursing and midwifery knowledge in recent years. A sequential exploratory design is used as an exemplar of a mixed methods approach. The study discussed used a combination of focus-group interviews and a quantitative instrument to obtain a fuller understanding of women's experiences of childbirth. In the mixed methods study example, qualitative data were analysed using thematic analysis and quantitative data using regression analysis. Polarised debates about the veracity, philosophical integrity and motivation for conducting mixed methods research have largely abated. A mixed methods approach can contribute to a deeper, more contextual understanding of a variety of subjects and experiences; as a result, it furthers knowledge that can be used in clinical practice. The purpose of the research study should be the main instigator when choosing from an array of mixed methods research designs. Mixed methods research offers a variety of models that can augment investigative capabilities and provide richer data than can a discrete method alone. This paper offers an example of an exploratory, sequential approach to investigating women's childbirth experiences. A clear framework for the conduct and integration of the different phases of the mixed methods research process is provided. This approach can be used by practitioners and policy makers to improve practice.

  4. Method for innovative synthesis-design of chemical process flowsheets

    DEFF Research Database (Denmark)

    Kumar Tula, Anjan; Gani, Rafiqul

    Chemical process synthesis-design involve the identification of the processing route to reach a desired product from a specified set of raw materials, design of the operations involved in the processing route, the calculations of utility requirements, the calculations of waste and emission...... to the surrounding and many more. Different methods (knowledge-based [1], mathematical programming [2], hybrid, etc.) have been proposed and are also currently employed to solve these synthesis-design problems. D’ Anterroches [3] proposed a group contribution based approach to solve the synthesis-design problem...... of chemical processes, where, chemical process flowsheets could be synthesized in the same way as atoms or groups of atoms are synthesized to form molecules in computer aided molecular design (CAMD) techniques [4]. That, from a library of building blocks (functional process-groups) and a set of rules to join...

  5. Conference on Manned Systems Design : New Methods and Equipment

    CERN Document Server

    Kraiss, K-F

    1981-01-01

    This volume contains the proceedings of a conference held in Freiburg, West Germany, September 22-25, 1980, entitled "Manned Systems Design, New Methods and Equipment". The conference was sponsored by the Special Programme Panel on Human Factors of the Scientific Affairs Division of NATO, and supported by Panel VIII, AC/243, on "Human and Biomedical Sciences". Their sponsorship and support are gratefully acknowledged. The contributions in the book are grouped according to the main themes of the conference with special emphasis on analytical approaches, measurement of performance, and simulator design and evaluat ion. The design of manned systems covers many and highly diversified areas. Therefore, a conference under the general title of "Manned Systems Design" is rather ambitious in itself. However, scientists and engineers engaged in the design of manned systems very often are confronted with problems that can be solved only by having several disciplines working together. So it was felt that knowledge about ...

  6. A standardized method for beam design in neutron capture therapy

    International Nuclear Information System (INIS)

    Storr, G.J.: Harrington, B.V.

    1993-01-01

    A desirable end point for a given beam design for Neutron Capture Therapy (NCT) should be quantitative description of tumour control probability and normal tissue damage. Achieving this goal will ultimately rely on data from NCT human clinical trials. Traditional descriptions of beam designs have used a variety of assessment methods to quantify proposed or installed beam designs. These methods include measurement and calculation of open-quotes free fieldclose quotes parameters, such as neutron and gamma flux intensities and energy spectra, and figures-of-merit in tissue equivalent phantoms. The authors propose here a standardized method for beam design in NCT. This method would allow all proposed and existing NCT beam facilities to be compared equally. The traditional approach to determining a quantitative description of tumour control probability and normal tissue damage in NCT research may be described by the following path: Beam design → dosimetry → macroscopic effects → microscopic effects. Methods exist that allow neutron and gamma fluxes and energy dependence to be calculated and measured to good accuracy. By using this information and intermediate dosimetric quantities such as kerma factors for neutrons and gammas, macroscopic effect (absorbed dose) in geometries of tissue or tissue-equivalent materials can be calculated. After this stage, for NCT the data begins to become more sparse and in some areas ambiguous. Uncertainties in the Relative Biological Effectiveness (RBE) of some NCT dose components means that beam designs based on assumptions considered valid a few years ago may have to be reassessed. A standard method is therefore useful for comparing different NCT facilities

  7. Design and Evaluation Methods for Underwater Control Systems

    Energy Technology Data Exchange (ETDEWEB)

    Chi, Lin

    1996-12-31

    This thesis on underwater control systems is written with the designer in mind, assuming that the reader has some knowledge of control theory. It can be used as a text for undergraduate students and engineers. To help readers better understand the system they will be working with, the thesis is organised in a stepwise way. The reader will gain basic knowledge about underwater operations, equipment and control systems. Then the reader will be able to follow the steps to develop a required control system for an underwater equipment by first understanding the characteristics of the design problem, customer requirement, functional requirement, and possible solution, and then to present a mathematical model of the control problem. Having developed the concept, the thesis guides the reader to develop evaluation criteria and different ways to make the decision. The thesis gives an overview of how to achieve a successful design rather than giving the techniques for detailed control system design. Chapter 1 describes underwater operations and systems. Chapter 2 discusses issues of underwater control systems and control methods. Chapter 3 deals with design method and control systems theory, focusing on human-centered control. Chapter 4 discusses methods used to evaluate and rank products, and chapter 5 applies the methods to an example. 113 refs., 115 figs., 80 tabs.

  8. Design and Evaluation Methods for Underwater Control Systems

    Energy Technology Data Exchange (ETDEWEB)

    Chi, Lin

    1997-12-31

    This thesis on underwater control systems is written with the designer in mind, assuming that the reader has some knowledge of control theory. It can be used as a text for undergraduate students and engineers. To help readers better understand the system they will be working with, the thesis is organised in a stepwise way. The reader will gain basic knowledge about underwater operations, equipment and control systems. Then the reader will be able to follow the steps to develop a required control system for an underwater equipment by first understanding the characteristics of the design problem, customer requirement, functional requirement, and possible solution, and then to present a mathematical model of the control problem. Having developed the concept, the thesis guides the reader to develop evaluation criteria and different ways to make the decision. The thesis gives an overview of how to achieve a successful design rather than giving the techniques for detailed control system design. Chapter 1 describes underwater operations and systems. Chapter 2 discusses issues of underwater control systems and control methods. Chapter 3 deals with design method and control systems theory, focusing on human-centered control. Chapter 4 discusses methods used to evaluate and rank products, and chapter 5 applies the methods to an example. 113 refs., 115 figs., 80 tabs.

  9. Improving Battery Reactor Core Design Using Optimization Method

    International Nuclear Information System (INIS)

    Son, Hyung M.; Suh, Kune Y.

    2011-01-01

    The Battery Omnibus Reactor Integral System (BORIS) is a small modular fast reactor being designed at Seoul National University to satisfy various energy demands, to maintain inherent safety by liquid-metal coolant lead for natural circulation heat transport, and to improve power conversion efficiency with the Modular Optimal Balance Integral System (MOBIS) using the supercritical carbon dioxide as working fluid. This study is focused on developing the Neutronics Optimized Reactor Analysis (NORA) method that can quickly generate conceptual design of a battery reactor core by means of first principle calculations, which is part of the optimization process for reactor assembly design of BORIS

  10. Computer Aided Flowsheet Design using Group Contribution Methods

    DEFF Research Database (Denmark)

    Bommareddy, Susilpa; Eden, Mario R.; Gani, Rafiqul

    2011-01-01

    In this paper, a systematic group contribution based framework is presented for synthesis of process flowsheets from a given set of input and output specifications. Analogous to the group contribution methods developed for molecular design, the framework employs process groups to represent...... information of each flowsheet to minimize the computational load and information storage. The design variables for the selected flowsheet(s) are identified through a reverse simulation approach and are used as initial estimates for rigorous simulation to verify the feasibility and performance of the design....

  11. Design methods and criteria recommended by the RAMSES committee

    International Nuclear Information System (INIS)

    Jakubowicz, H.; Moulin, D.; Petrequin, P.; Tortel, J.; Schaller, K.

    1980-09-01

    The design of structures of LMFBR in France must comply with the national regulations and takes into account the rules adopted by other countries but these rules need complements. The French Atomic Energy Commission has founded a committee named RAMSES (which states for 'Regles d'Analyse Mecanique des Structures') in order to write recommendations to give out the needed informations on design rules based on all the available background experience. The elastic follow up problem has received great attention and a recommendation was already printed. Of great concern in elevated temperature is a creep fatigue investigation. A creep fatigue design method adapted to materials used is being set up

  12. Using protein design algorithms to understand the molecular basis of disease caused by protein-DNA interactions: the Pax6 example

    DEFF Research Database (Denmark)

    Alibes, A.; Nadra, A.; De Masi, Federico

    2010-01-01

    diseases such as aniridia. The validity of FoldX to deal with protein-DNA interactions was demonstrated by showing that high levels of accuracy can be achieved for mutations affecting these interactions. Also we showed that protein-design algorithms can accurately reproduce experimental DNA-binding logos......Quite often a single or a combination of protein mutations is linked to specific diseases. However, distinguishing from sequence information which mutations have real effects in the protein's function is not trivial. Protein design tools are commonly used to explain mutations that affect protein...... stability, or protein-protein interaction, but not for mutations that could affect protein-DNA binding. Here, we used the protein design algorithm FoldX to model all known missense mutations in the paired box domain of Pax6, a highly conserved transcription factor involved in eye development and in several...

  13. Precision die design by the die expansion method

    CERN Document Server

    Ibhadode, A O Akii

    2009-01-01

    This book presents a new method for the design of the precision dies used in cold-forging, extrusion and drawing processes. The method is based upon die expansion, and attempts to provide a clear-cut theoretical basis for the selection of critical die dimensions for this group of precision dies when the tolerance on product diameter (or thickness) is specified. It also presents a procedure for selecting the minimum-production-cost die from among a set of design alternatives. The mathematical content of the book is relatively simple and will present no difficulty to those who have taken basic c

  14. Targeting a heterologous protein to multiple plant organelles via rationally designed 5? mRNA tags

    NARCIS (Netherlands)

    Voges, M.J.; Silver, P.A.; Way, J.C.; Mattozzi, M.D.

    2013-01-01

    Background Plant bioengineers require simple genetic devices for predictable localization of heterologous proteins to multiple subcellular compartments. Results We designed novel hybrid signal sequences for multiple-compartment localization and characterize their function when fused to GFP in

  15. Electrochemical and spectroscopic investigations of immobilized de novo designed heme proteins on metal electrodes

    DEFF Research Database (Denmark)

    Albrecht, Tim; Li, WW; Ulstrup, Jens

    2005-01-01

    On the basis of rational design principles, template-assisted four-helix-bundle proteins that include two histidines for coordinative binding of a heme were synthesized. Spectroscopic and thermodynamic characterization of the proteins in solution reveals the expected bis-histidine coordinated heme...

  16. Modification of design methods to suit computer aided design of pumps

    International Nuclear Information System (INIS)

    Kumaraswamy, S.

    1994-01-01

    Engineering designs involve a large number of repetitive calculations to achieve optimisation. So, computers which are fast and accurate lend themselves as an aid for the design process. However, certain modifications in the steps of conventional design method become necessary for easier adaptation. In addition, it will be advantageous if the empirical coefficients of design are allowed to be chosen by the designer with prompting of ranges taken from design charts by the program itself. This paper describes two examples of modification in pump design. In the first case Anderson's area ratio method and Pfleiderer's Slip power methods are combined to achieve an integrated design of impeller and casing. The second case is the design of a Mixed flow pump impeller by considering it as an assembly of a number of radial flow pump impellers called part impellers. In addition, these modifications are useful in redesign for a different operating condition or in matching of impellers to existing casings. (author). 13 refs., 4 figs

  17. Modeling and design of light powered biomimicry micropump utilizing transporter proteins

    Science.gov (United States)

    Liu, Jin; Sze, Tsun-Kay Jackie; Dutta, Prashanta

    2014-11-01

    The creation of compact micropumps to provide steady flow has been an on-going challenge in the field of microfluidics. We present a mathematical model for a micropump utilizing Bacteriorhodopsin and sugar transporter proteins. This micropump utilizes transporter proteins as method to drive fluid flow by converting light energy into chemical potential. The fluid flow through a microchannel is simulated using the Nernst-Planck, Navier-Stokes, and continuity equations. Numerical results show that the micropump is capable of generating usable pressure. Designing parameters influencing the performance of the micropump are investigated including membrane fraction, lipid proton permeability, illumination, and channel height. The results show that there is a substantial membrane fraction region at which fluid flow is maximized. The use of lipids with low membrane proton permeability allows illumination to be used as a method to turn the pump on and off. This capability allows the micropump to be activated and shut off remotely without bulky support equipment. This modeling work provides new insights on mechanisms potentially useful for fluidic pumping in self-sustained bio-mimic microfluidic pumps. This work is supported in part by the National Science Fundation Grant CBET-1250107.

  18. Analysis of protein profiles using fuzzy clustering methods

    DEFF Research Database (Denmark)

    Karemore, Gopal Raghunath; Ukendt, Sujatha; Rai, Lavanya

    The tissue protein profiles of healthy volunteers and volunteers with cervical cancer were recorded using High Performance Liquid Chromatography combined with Laser Induced Fluorescence  technique  (HPLC-LIF)  developed  in  our  lab.      We analyzed      the protein profile data using different...

  19. Synthesis of Gold Nanoparticles to Capture Lifelike Proteins: Application on the Multichannel Sensor Array Design

    Directory of Open Access Journals (Sweden)

    Yumin Leng

    2018-01-01

    Full Text Available The chemical elements of proteins are similar to that of DNA (e.g., C, H, O, and N, and DNA shows different knotted architectures. So we imagine that proteins may show a wealth of highly complex structures, especially when proteins interact with each other. The imagination was proved by synthesizing gold nanoparticles (GNPs to capture the lifelike protein structures. The optical responses (i.e., color of as-prepared GNPs are found to be characteristic to a given protein (or heavy metal ion. Based on the “three colors” principle of Thomas Young, we extracted the red, green, and blue (RGB alterations of as-synthesized GNPs to fabricate multichannel sensor arrays for proteins (or heavy metal ions discrimination. The designed multichannel sensor arrays demonstrate possibilities in semiquantitative analysis of multiple analytes (e.g., proteins and heavy metal ions. This work is believed to open new opportunities for GNPs-based label-free sensing.

  20. Addressing Research Design Problem in Mixed Methods Research

    Science.gov (United States)

    Alavi, Hamed; Hąbek, Patrycja

    2016-03-01

    Alongside other disciplines in social sciences, management researchers use mixed methods research more and more in conduct of their scientific investigations. Mixed methods approach can also be used in the field of production engineering. In comparison with traditional quantitative and qualitative research methods, reasons behind increasing popularity of mixed research method in management science can be traced in different factors. First of all, any particular discipline in management can be theoretically related to it. Second is that concurrent approach of mixed research method to inductive and deductive research logic provides researchers with opportunity to generate theory and test hypothesis in one study simultaneously. In addition, it provides a better justification for chosen method of investigation and higher validity for obtained answers to research questions. Despite increasing popularity of mixed research methods among management scholars, there is still need for a comprehensive approach to research design typology and process in mixed research method from the perspective of management science. The authors in this paper try to explain fundamental principles of mixed research method, its typology and different steps in its design process.

  1. New method for designing serial resonant power converters

    Science.gov (United States)

    Hinov, Nikolay

    2017-12-01

    In current work is presented one comprehensive method for design of serial resonant energy converters. The method is based on new simplified approach in analysis of such kind power electronic devices. It is grounded on supposing resonant mode of operation when finding relation between input and output voltage regardless of other operational modes (when controlling frequency is below or above resonant frequency). This approach is named `quasiresonant method of analysis', because it is based on assuming that all operational modes are `sort of' resonant modes. An estimation of error was made because of the a.m. hypothesis and is compared to the classic analysis. The `quasiresonant method' of analysis gains two main advantages: speed and easiness in designing of presented power circuits. Hence it is very useful in practice and in teaching Power Electronics. Its applicability is proven with mathematic modelling and computer simulation.

  2. Elucidating the design principles of photosynthetic electron-transfer proteins by site-directed spin labeling EPR spectroscopy.

    Science.gov (United States)

    Ishara Silva, K; Jagannathan, Bharat; Golbeck, John H; Lakshmi, K V

    2016-05-01

    Site-directed spin labeling electron paramagnetic resonance (SDSL EPR) spectroscopy is a powerful tool to determine solvent accessibility, side-chain dynamics, and inter-spin distances at specific sites in biological macromolecules. This information provides important insights into the structure and dynamics of both natural and designed proteins and protein complexes. Here, we discuss the application of SDSL EPR spectroscopy in probing the charge-transfer cofactors in photosynthetic reaction centers (RC) such as photosystem I (PSI) and the bacterial reaction center (bRC). Photosynthetic RCs are large multi-subunit proteins (molecular weight≥300 kDa) that perform light-driven charge transfer reactions in photosynthesis. These reactions are carried out by cofactors that are paramagnetic in one of their oxidation states. This renders the RCs unsuitable for conventional nuclear magnetic resonance spectroscopy investigations. However, the presence of native paramagnetic centers and the ability to covalently attach site-directed spin labels in RCs makes them ideally suited for the application of SDSL EPR spectroscopy. The paramagnetic centers serve as probes of conformational changes, dynamics of subunit assembly, and the relative motion of cofactors and peptide subunits. In this review, we describe novel applications of SDSL EPR spectroscopy for elucidating the effects of local structure and dynamics on the electron-transfer cofactors of photosynthetic RCs. Because SDSL EPR Spectroscopy is uniquely suited to provide dynamic information on protein motion, it is a particularly useful method in the engineering and analysis of designed electron transfer proteins and protein networks. This article is part of a Special Issue entitled Biodesign for Bioenergetics--the design and engineering of electronic transfer cofactors, proteins and protein networks, edited by Ronald L. Koder and J.L. Ross Anderson. Copyright © 2016. Published by Elsevier B.V.

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

    Science.gov (United States)

    Chen, Bor-Sen; Wu, Chih-Hung

    2009-06-30

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

  4. In search of new lead compounds for trypanosomiasis drug design: A protein structure-based linked-fragment approach

    Science.gov (United States)

    Verlinde, Christophe L. M. J.; Rudenko, Gabrielle; Hol, Wim G. J.

    1992-04-01

    A modular method for pursuing structure-based inhibitor design in the framework of a design cycle is presented. The approach entails four stages: (1) a design pathway is defined in the three-dimensional structure of a target protein; (2) this pathway is divided into subregions; (3) complementary building blocks, also called fragments, are designed in each subregion; complementarity is defined in terms of shape, hydrophobicity, hydrogen bond properties and electrostatics; and (4) fragments from different subregions are linked into potential lead compounds. Stages (3) and (4) are qualitatively guided by force-field calculations. In addition, the designed fragments serve as entries for retrieving existing compounds from chemical databases. This linked-fragment approach has been applied in the design of potentially selective inhibitors of triosephosphate isomerase from Trypanosoma brucei, the causative agent of sleeping sickness.

  5. An adaptive bin framework search method for a beta-sheet protein homopolymer model

    Directory of Open Access Journals (Sweden)

    Hoos Holger H

    2007-04-01

    Full Text Available Abstract Background The problem of protein structure prediction consists of predicting the functional or native structure of a protein given its linear sequence of amino acids. This problem has played a prominent role in the fields of biomolecular physics and algorithm design for over 50 years. Additionally, its importance increases continually as a result of an exponential growth over time in the number of known protein sequences in contrast to a linear increase in the number of determined structures. Our work focuses on the problem of searching an exponentially large space of possible conformations as efficiently as possible, with the goal of finding a global optimum with respect to a given energy function. This problem plays an important role in the analysis of systems with complex search landscapes, and particularly in the context of ab initio protein structure prediction. Results In this work, we introduce a novel approach for solving this conformation search problem based on the use of a bin framework for adaptively storing and retrieving promising locally optimal solutions. Our approach provides a rich and general framework within which a broad range of adaptive or reactive search strategies can be realized. Here, we introduce adaptive mechanisms for choosing which conformations should be stored, based on the set of conformations already stored in memory, and for biasing choices when retrieving conformations from memory in order to overcome search stagnation. Conclusion We show that our bin framework combined with a widely used optimization method, Monte Carlo search, achieves significantly better performance than state-of-the-art generalized ensemble methods for a well-known protein-like homopolymer model on the face-centered cubic lattice.

  6. Interpretation of biological and mechanical variations between the Lowry versus Bradford method for protein quantification.

    Science.gov (United States)

    Lu, Tzong-Shi; Yiao, Szu-Yu; Lim, Kenneth; Jensen, Roderick V; Hsiao, Li-Li

    2010-07-01

    The identification of differences in protein expression resulting from methodical variations is an essential component to the interpretation of true, biologically significant results. We used the Lowry and Bradford methods- two most commonly used methods for protein quantification, to assess whether differential protein expressions are a result of true biological or methodical variations. MATERIAL #ENTITYSTARTX00026; Differential protein expression patterns was assessed by western blot following protein quantification by the Lowry and Bradford methods. We have observed significant variations in protein concentrations following assessment with the Lowry versus Bradford methods, using identical samples. Greater variations in protein concentration readings were observed over time and in samples with higher concentrations, with the Bradford method. Identical samples quantified using both methods yielded significantly different expression patterns on Western blot. We show for the first time that methodical variations observed in these protein assay techniques, can potentially translate into differential protein expression patterns, that can be falsely taken to be biologically significant. Our study therefore highlights the pivotal need to carefully consider methodical approaches to protein quantification in techniques that report quantitative differences.

  7. Function combined method for design innovation of children's bike

    Science.gov (United States)

    Wu, Xiaoli; Qiu, Tingting; Chen, Huijuan

    2013-03-01

    As children mature, bike products for children in the market develop at the same time, and the conditions are frequently updated. Certain problems occur when using a bike, such as cycle overlapping, repeating function, and short life cycle, which go against the principles of energy conservation and the environmental protection intensive design concept. In this paper, a rational multi-function method of design through functional superposition, transformation, and technical implementation is proposed. An organic combination of frog-style scooter and children's tricycle is developed using the multi-function method. From the ergonomic perspective, the paper elaborates on the body size of children aged 5 to 12 and effectively extracts data for a multi-function children's bike, which can be used for gliding and riding. By inverting the body, parts can be interchanged between the handles and the pedals of the bike. Finally, the paper provides a detailed analysis of the components and structural design, body material, and processing technology of the bike. The study of Industrial Product Innovation Design provides an effective design method to solve the bicycle problems, extends the function problems, improves the product market situation, and enhances the energy saving feature while implementing intensive product development effectively at the same time.

  8. OLP embedment design method research for AP1000 nuclear plant

    International Nuclear Information System (INIS)

    Li Cheng; Li Shaoping; Liu Jianwei

    2013-01-01

    Background: One of the most advanced nuclear power technology, the first AP1000 reactor is under construction in China. Modularization is one of the main characteristics for AP1000 nuclear plant building. Module wall with steel face plate is used instead of reinforced concrete structure wall. A number of OLP embedments need to be installed into the module wall to connect other structures such as pipes, equipment, operation platforms and any other component attached to the module wall. Therefore, the design of embedment is very important in AP1000 structural design. Purpose: A finite element analysis method and tool for embedment design is needed for convenience. Methods: This paper applies the self-developed GTStrudl command template and VBA macro program for embedment capacity calculation and evaluation based on Microsoft Excel to the embedment design. Results: A Microsoft Excel template for embedment design is developed. Conclusions: The analysis method and template brings reasonable results and may provide some help and use for reference for the engineering practice. (authors)

  9. Nitrosative Stress in the Nervous System: Guidelines for Designing Experimental Strategies to Study Protein S-Nitrosylation.

    Science.gov (United States)

    Nakamura, Tomohiro; Lipton, Stuart A

    2016-03-01

    Reactive nitrogen species, such as nitric oxide (NO), exert their biological activity in large part through post-translational modification of cysteine residues, forming S-nitrosothiols. This chemical reaction proceeds via a process that we and our colleagues have termed protein S-nitrosylation. Under conditions of normal NO production, S-nitrosylation regulates the activity of many normal proteins. However, in degenerative conditions characterized by nitrosative stress, increased levels of NO lead to aberrant S-nitrosylation that contributes to the pathology of the disease. Thus, S-nitrosylation has been implicated in a wide range of cellular mechanisms, including mitochondrial function, proteostasis, transcriptional regulation, synaptic activity, and cell survival. In recent years, the research area of protein S-nitrosylation has become prominent due to improvements in the detection systems as well as the demonstration that protein S-nitrosylation plays a critical role in the pathogenesis of neurodegenerative and other neurological disorders. To further promote our understanding of how protein S-nitrosylation affects cellular systems, guidelines for the design and conduct of research on S-nitrosylated (or SNO-)proteins would be highly desirable, especially for those newly entering the field. In this review article, we provide a strategic overview of designing experimental approaches to study protein S-nitrosylation. We specifically focus on methods that can provide critical data to demonstrate that an S-nitrosylated protein plays a (patho-)physiologically-relevant role in a biological process. Hence, the implementation of the approaches described herein will contribute to further advancement of the study of S-nitrosylated proteins, not only in neuroscience but also in other research fields.

  10. A Simple Method for High-Lift Propeller Conceptual Design

    Science.gov (United States)

    Patterson, Michael; Borer, Nick; German, Brian

    2016-01-01

    In this paper, we present a simple method for designing propellers that are placed upstream of the leading edge of a wing in order to augment lift. Because the primary purpose of these "high-lift propellers" is to increase lift rather than produce thrust, these props are best viewed as a form of high-lift device; consequently, they should be designed differently than traditional propellers. We present a theory that describes how these props can be designed to provide a relatively uniform axial velocity increase, which is hypothesized to be advantageous for lift augmentation based on a literature survey. Computational modeling indicates that such propellers can generate the same average induced axial velocity while consuming less power and producing less thrust than conventional propeller designs. For an example problem based on specifications for NASA's Scalable Convergent Electric Propulsion Technology and Operations Research (SCEPTOR) flight demonstrator, a propeller designed with the new method requires approximately 15% less power and produces approximately 11% less thrust than one designed for minimum induced loss. Higher-order modeling and/or wind tunnel testing are needed to verify the predicted performance.

  11. Design Method of Active Disturbance Rejection Variable Structure Control System

    Directory of Open Access Journals (Sweden)

    Yun-jie Wu

    2015-01-01

    Full Text Available Based on lines cluster approaching theory and inspired by the traditional exponent reaching law method, a new control method, lines cluster approaching mode control (LCAMC method, is designed to improve the parameter simplicity and structure optimization of the control system. The design guidelines and mathematical proofs are also given. To further improve the tracking performance and the inhibition of the white noise, connect the active disturbance rejection control (ADRC method with the LCAMC method and create the extended state observer based lines cluster approaching mode control (ESO-LCAMC method. Taking traditional servo control system as example, two control schemes are constructed and two kinds of comparison are carried out. Computer simulation results show that LCAMC method, having better tracking performance than the traditional sliding mode control (SMC system, makes the servo system track command signal quickly and accurately in spite of the persistent equivalent disturbances and ESO-LCAMC method further reduces the tracking error and filters the white noise added on the system states. Simulation results verify the robust property and comprehensive performance of control schemes.

  12. Structure for Categorization of EcoDesign Methods and Tools

    OpenAIRE

    Lindahl, Mattias; Ekermann, Sara

    2013-01-01

    This edited volume presents the proceedings of the 20th CIRP LCE Conference, which cover various areas in life cycle engineering such as life cycle design, end-of-life management, manufacturing processes, manufacturing systems, methods and tools for sustainability, social sustainability, supply chain management, remanufacturing,

  13. ASSESSMENT OF WORK-SPACE AND WORK-METHOD DESIGNS ...

    African Journals Online (AJOL)

    related injuries among its workforce. This research assessed work-space (WsD) and work-method designs (WmD), level of compliance with recommended standards (RSs) and effects on workers' wellbeing. Clearances for services in 55 supine ...

  14. Methods for the neutronic design of a Supersara experimental loop

    International Nuclear Information System (INIS)

    Casali, F.; Cepraga, D.

    1982-01-01

    This paper describes a method for the neutronic design of experimental loops irradiated in D 2 O experimental reactors, like Essor. The calculation approach concerns the definition of a Weigner-Seitz cell where the loop under examination be subjected to the same neutronic conditions as in the actual reactor

  15. General method for final focus system design for circular colliders

    Directory of Open Access Journals (Sweden)

    Riccardo de Maria

    2008-03-01

    Full Text Available Colliders use final focus systems to reduce the transverse beam sizes at the interaction point in order to increase collision event rates. The maximum focal strength (gradient of the quadrupoles, and the maximum beam size in them, together limit the beam size reduction that is possible. The goal of a final focus system design is to find the best compromise between quadrupole aperture and quadrupole gradient, for the magnet technology that is used. This paper develops a design method that identifies the intrinsic limitations of a final focus system, validates the results of the method against realistic designs, and reports its application to the upgrade of the Large Hadron Collider final focus.

  16. Harbourscape Aalborg - Design Based Methods in Waterfront Development

    DEFF Research Database (Denmark)

    Kiib, Hans

    2012-01-01

    How can city planners and developers gain knowledge and develop new sustainable concepts for water front developments? The waterfront is far too often threatened by new privatisation, lack of public access and bad architecture. And in a time where low growth rates and crises in the building...... industry is leaving great parts of the harbour as urban voids planners are in search of new tools for bridging the time gap until new projects can be a reality. This chapter presents the development of waterfront regeneration concepts that resulted from design based workshops, Harbourscape Aalborg in 2005...... and Performative Architecture Workshop in 2008, and evaluates the method and the thinking behind this. The design workshops provide different design-based development methods which can be tested with the purpose of developing new concepts for the relationship between the city and its harbour, and in addition...

  17. Linearization of the Bradford protein assay to application in cow milk proteins quantification by UV-Vis spectrophotometry method.

    OpenAIRE

    SANTOS, A. S. de O. dos; COSTA, F. F.; ESTEVES, W. T.; BRITO, M. A. V. P. e; FURTADO, M. A. M.; MARTINS, M. F.

    2015-01-01

    Reliable methods for determination and quantification of total protein in food are essential information to ensure quality and safety of food trade. The objective of this study was to evaluate the linearity of calibration curves obtained from different proteins (blood serum albumin-BSA, α-LA, β-LG, αs, β and κ-CAS) with the reagent of Bradford. Comercial UHT skimmed bovine milk was analyzed for the determination of total protein using the Bradford method by reading at 595 nm. The determinatio...

  18. Comparison of optimal design methods in inverse problems

    International Nuclear Information System (INIS)

    Banks, H T; Holm, K; Kappel, F

    2011-01-01

    Typical optimal design methods for inverse or parameter estimation problems are designed to choose optimal sampling distributions through minimization of a specific cost function related to the resulting error in parameter estimates. It is hoped that the inverse problem will produce parameter estimates with increased accuracy using data collected according to the optimal sampling distribution. Here we formulate the classical optimal design problem in the context of general optimization problems over distributions of sampling times. We present a new Prohorov metric-based theoretical framework that permits one to treat succinctly and rigorously any optimal design criteria based on the Fisher information matrix. A fundamental approximation theory is also included in this framework. A new optimal design, SE-optimal design (standard error optimal design), is then introduced in the context of this framework. We compare this new design criterion with the more traditional D-optimal and E-optimal designs. The optimal sampling distributions from each design are used to compute and compare standard errors; the standard errors for parameters are computed using asymptotic theory or bootstrapping and the optimal mesh. We use three examples to illustrate ideas: the Verhulst–Pearl logistic population model (Banks H T and Tran H T 2009 Mathematical and Experimental Modeling of Physical and Biological Processes (Boca Raton, FL: Chapman and Hall/CRC)), the standard harmonic oscillator model (Banks H T and Tran H T 2009) and a popular glucose regulation model (Bergman R N, Ider Y Z, Bowden C R and Cobelli C 1979 Am. J. Physiol. 236 E667–77; De Gaetano A and Arino O 2000 J. Math. Biol. 40 136–68; Toffolo G, Bergman R N, Finegood D T, Bowden C R and Cobelli C 1980 Diabetes 29 979–90)

  19. Comparison of optimal design methods in inverse problems

    Science.gov (United States)

    Banks, H. T.; Holm, K.; Kappel, F.

    2011-07-01

    Typical optimal design methods for inverse or parameter estimation problems are designed to choose optimal sampling distributions through minimization of a specific cost function related to the resulting error in parameter estimates. It is hoped that the inverse problem will produce parameter estimates with increased accuracy using data collected according to the optimal sampling distribution. Here we formulate the classical optimal design problem in the context of general optimization problems over distributions of sampling times. We present a new Prohorov metric-based theoretical framework that permits one to treat succinctly and rigorously any optimal design criteria based on the Fisher information matrix. A fundamental approximation theory is also included in this framework. A new optimal design, SE-optimal design (standard error optimal design), is then introduced in the context of this framework. We compare this new design criterion with the more traditional D-optimal and E-optimal designs. The optimal sampling distributions from each design are used to compute and compare standard errors; the standard errors for parameters are computed using asymptotic theory or bootstrapping and the optimal mesh. We use three examples to illustrate ideas: the Verhulst-Pearl logistic population model (Banks H T and Tran H T 2009 Mathematical and Experimental Modeling of Physical and Biological Processes (Boca Raton, FL: Chapman and Hall/CRC)), the standard harmonic oscillator model (Banks H T and Tran H T 2009) and a popular glucose regulation model (Bergman R N, Ider Y Z, Bowden C R and Cobelli C 1979 Am. J. Physiol. 236 E667-77 De Gaetano A and Arino O 2000 J. Math. Biol. 40 136-68 Toffolo G, Bergman R N, Finegood D T, Bowden C R and Cobelli C 1980 Diabetes 29 979-90).

  20. LINEARIZATION OF THE BRADFORD PROTEIN ASSAY TO APPLICATION IN COW MILK PROTEINS QUANTIFICATION BY UV-Vis SPECTROPHOTOMETRY METHOD

    Directory of Open Access Journals (Sweden)

    Alessa Siqueira de Oliveira dos Santos

    2015-01-01

    Full Text Available Reliable methods for determination and quantification of total protein in food are essential information to ensure quality and safety of food trade. The objective of this study was to evaluate the linearity of calibration curves obtained from different proteins (blood serum albumin-BSA, α-LA, β-LG, caseins (CN: αs, β and κ-CAS with the reagent of Bradford. Comercial UHT skimmed bovine milk was analyzed for the determination of total protein using the Bradford method by reading at 595 nm. The determination of the concentrations of total milk protein was achieved by linear regression. The Bradford method showed a high sensitivity for the determination of total proteins in bovine milk dilution 1:25 to values closer to those obtained by the Kjeldahl method. The results showed that the calibration curve of standard proteins β-CN and BSA obtained better linearity with less variation in the absorbance measurements for the determination of total protein of milk.

  1. Conceptual design of krypton recovery plant by porous membrane method

    International Nuclear Information System (INIS)

    Yoshida, Hiroshi; Fujine, Sachio; Shimizu, Toku; Saito, Keiichiro; Ouchi, Misao

    1979-10-01

    A conceptual design of a krypton recovery plant by porous membrane method was made to study feasibility of treating fuel reprocessing off-gas. Specifications of the plant could be clarified, such as off-gas pretreatment system, first cascade system of gaseous diffusion Hertz cascade composed of two-compartment diffusers, storage system, shield and housing and operating conditions. Capital costs and operating costs of the plant were estimated for different operating conditions and cost parameters. Technical and economic feasibility of the method compares favorably with those of the cryogenic distillation or the solvent absorption method. (author)

  2. Designing stellarator coils by a modified Newton method using FOCUS

    Science.gov (United States)

    Zhu, Caoxiang; Hudson, Stuart R.; Song, Yuntao; Wan, Yuanxi

    2018-06-01

    To find the optimal coils for stellarators, nonlinear optimization algorithms are applied in existing coil design codes. However, none of these codes have used the information from the second-order derivatives. In this paper, we present a modified Newton method in the recently developed code FOCUS. The Hessian matrix is calculated with analytically derived equations. Its inverse is approximated by a modified Cholesky factorization and applied in the iterative scheme of a classical Newton method. Using this method, FOCUS is able to recover the W7-X modular coils starting from a simple initial guess. Results demonstrate significant advantages.

  3. Inverse design-momentum, a method for the preliminary design of horizontal axis wind turbines

    International Nuclear Information System (INIS)

    Battisti, L; Soraperra, G; Fedrizzi, R; Zanne, L

    2007-01-01

    Wind turbine rotor prediction methods based on generalized momentum theory BEM routinely used in industry and vortex wake methods demand the use of airfoil tabulated data and geometrical specifications such as the blade spanwise chord distribution. They belong to the category of 'direct design' methods. When, on the other hand, the geometry is deduced from some design objective, we refer to 'inverse design' methods. This paper presents a method for the preliminary design of wind turbine rotors based on an inverse design approach. For this purpose, a generalized theory was developed without using classical tools such as BEM. Instead, it uses a simplified meridional flow analysis of axial turbomachines and is based on the assumption that knowing the vortex distribution and appropriate boundary conditions is tantamount to knowing the velocity distribution. The simple conservation properties of the vortex components consistently cope with the forces and specific work exchange expressions through the rotor. The method allows for rotor arbitrarily radial load distribution and includes the wake rotation and expansion. Radial pressure gradient is considered in the wake. The capability of the model is demonstrated first by a comparison with the classical actuator disk theory in investigating the consistency of the flow field, then the model is used to predict the blade planform of a commercial wind turbine. Based on these validations, the authors postulate the use of a different vortex distribution (i.e. not-uniform loading) for blade design and discuss the effect of such choices on blade chord and twist, force distribution and power coefficient. In addition to the method's straightforward application to the pre-design phase, the model clearly shows the link between blade geometry and performance allowing quick preliminary evaluation of non uniform loading on blade structural characteristics

  4. Design of tryptophan-containing mutants of the symmetrical Pizza protein for biophysical studies.

    Science.gov (United States)

    Noguchi, Hiroki; Mylemans, Bram; De Zitter, Elke; Van Meervelt, Luc; Tame, Jeremy R H; Voet, Arnout

    2018-03-18

    β-propeller proteins are highly symmetrical, being composed of a repeated motif with four anti-parallel β-sheets arranged around a central axis. Recently we designed the first completely symmetrical β-propeller protein, Pizza6, consisting of six identical tandem repeats. Pizza6 is expected to prove a useful building block for bionanotechnology, and also a tool to investigate the folding and evolution of β-propeller proteins. Folding studies are made difficult by the high stability and the lack of buried Trp residues to act as monitor fluorophores, so we have designed and characterized several Trp-containing Pizza6 derivatives. In total four proteins were designed, of which three could be purified and characterized. Crystal structures confirm these mutant proteins maintain the expected structure, and a clear redshift of Trp fluorescence emission could be observed upon denaturation. Among the derivative proteins, Pizza6-AYW appears to be the most suitable model protein for future folding/unfolding kinetics studies as it has a comparable stability as natural β-propeller proteins. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Simple method for identification of plasmid-coded proteins

    International Nuclear Information System (INIS)

    Sancar, A.; Hack, A.M.; Rupp, W.D.

    1979-01-01

    Proteins encoded by plasmid DNA are specifically labeled in uv-irradiated cells of Escherichia coli carrying recA and uvrA mutations because extensive degradation of the chromosome DNA occurs concurrently with amplification of plasmid DNA

  6. Cloning an artificial gene encoding angiostatic anginex: From designed peptide to functional recombinant protein

    International Nuclear Information System (INIS)

    Brandwijk, Ricardo J.M.G.E.; Nesmelova, Irina; Dings, Ruud P.M.; Mayo, Kevin H.; Thijssen, Victor L.J.L.; Griffioen, Arjan W.

    2005-01-01

    Anginex, a designed peptide 33-mer, is a potent angiogenesis inhibitor and anti-tumor agent in vivo. Anginex functions by inhibiting endothelial cell (EC) proliferation and migration leading to detachment and apoptosis of activated EC's. To better understand tumor endothelium targeting properties of anginex and enable its use in gene therapy, we constructed an artificial gene encoding the biologically exogenous peptide and produced the protein recombinantly in Pichia pastoris. Mass spectrometry shows recombinant anginex to be a dimer and circular dichroism shows the recombinant protein folds with β-strand structure like the synthetic peptide. Moreover, like parent anginex, the recombinant protein is active at inhibiting EC growth and migration, as well as inhibiting angiogenesis in vivo in the chorioallantoic membrane of the chick embryo. This study demonstrated that it is possible to produce a functionally active protein version of a rationally designed peptide, using an artificial gene and the recombinant protein approach

  7. Iterative Refinement Methods for Time-Domain Equalizer Design

    Directory of Open Access Journals (Sweden)

    Evans Brian L

    2006-01-01

    Full Text Available Commonly used time domain equalizer (TEQ design methods have been recently unified as an optimization problem involving an objective function in the form of a Rayleigh quotient. The direct generalized eigenvalue solution relies on matrix decompositions. To reduce implementation complexity, we propose an iterative refinement approach in which the TEQ length starts at two taps and increases by one tap at each iteration. Each iteration involves matrix-vector multiplications and vector additions with matrices and two-element vectors. At each iteration, the optimization of the objective function either improves or the approach terminates. The iterative refinement approach provides a range of communication performance versus implementation complexity tradeoffs for any TEQ method that fits the Rayleigh quotient framework. We apply the proposed approach to three such TEQ design methods: maximum shortening signal-to-noise ratio, minimum intersymbol interference, and minimum delay spread.

  8. Numerical methods design, analysis, and computer implementation of algorithms

    CERN Document Server

    Greenbaum, Anne

    2012-01-01

    Numerical Methods provides a clear and concise exploration of standard numerical analysis topics, as well as nontraditional ones, including mathematical modeling, Monte Carlo methods, Markov chains, and fractals. Filled with appealing examples that will motivate students, the textbook considers modern application areas, such as information retrieval and animation, and classical topics from physics and engineering. Exercises use MATLAB and promote understanding of computational results. The book gives instructors the flexibility to emphasize different aspects--design, analysis, or computer implementation--of numerical algorithms, depending on the background and interests of students. Designed for upper-division undergraduates in mathematics or computer science classes, the textbook assumes that students have prior knowledge of linear algebra and calculus, although these topics are reviewed in the text. Short discussions of the history of numerical methods are interspersed throughout the chapters. The book a...

  9. Mixed methods research: a design for emergency care research?

    Science.gov (United States)

    Cooper, Simon; Porter, Jo; Endacott, Ruth

    2011-08-01

    This paper follows previous publications on generic qualitative approaches, qualitative designs and action research in emergency care by this group of authors. Contemporary views on mixed methods approaches are considered, with a particular focus on the design choice and the amalgamation of qualitative and quantitative data emphasising the timing of data collection for each approach, their relative 'weight' and how they will be mixed. Mixed methods studies in emergency care are reviewed before the variety of methodological approaches and best practice considerations are presented. The use of mixed methods in clinical studies is increasing, aiming to answer questions such as 'how many' and 'why' in the same study, and as such are an important and useful approach to many key questions in emergency care.

  10. A New Design Method for Industrial Portal Frames in Fire

    Directory of Open Access Journals (Sweden)

    Y. Song

    2009-01-01

    Full Text Available Industrial portal frames near to other buildings must keep their vertical walls standing in fire in order to prevent fire spread.  A recently developed analysis, implemented in the program Vulcan, using a combination of static and dynamic solvers, has shown that the strong base connections recommended by the current design method may not always lead to conservative design. A second-phase failure mechanism observed in numerical modelling, and the critical temperature at which final run-away collapse occurs, may be higher than the temperature at which the roof frame initially loses its stability, because a re-stabilisation often happens.  A new method for estimating critical temperatures of portal frames in fire, using these two failure mechanisms, is presented. Numerical tests on typical industrial frames are used to calibrate this new method

  11. Kinoform design with an optimal-rotation-angle method.

    Science.gov (United States)

    Bengtsson, J

    1994-10-10

    Kinoforms (i.e., computer-generated phase holograms) are designed with a new algorithm, the optimalrotation- angle method, in the paraxial domain. This is a direct Fourier method (i.e., no inverse transform is performed) in which the height of the kinoform relief in each discrete point is chosen so that the diffraction efficiency is increased. The optimal-rotation-angle algorithm has a straightforward geometrical interpretation. It yields excellent results close to, or better than, those obtained with other state-of-the-art methods. The optimal-rotation-angle algorithm can easily be modified to take different restraints into account; as an example, phase-swing-restricted kinoforms, which distribute the light into a number of equally bright spots (so called fan-outs), were designed. The phase-swing restriction lowers the efficiency, but the uniformity can still be made almost perfect.

  12. A Method for Design of Modular Reconfigurable Machine Tools

    Directory of Open Access Journals (Sweden)

    Zhengyi Xu

    2017-02-01

    Full Text Available Presented in this paper is a method for the design of modular reconfigurable machine tools (MRMTs. An MRMT is capable of using a minimal number of modules through reconfiguration to perform the required machining tasks for a family of parts. The proposed method consists of three steps: module identification, module determination, and layout synthesis. In the first step, the module components are collected from a family of general-purpose machines to establish a module library. In the second step, for a given family of parts to be machined, a set of needed modules are selected from the module library to construct a desired reconfigurable machine tool. In the third step, a final machine layout is decided though evaluation by considering a number of performance indices. Based on this method, a software package has been developed that can design an MRMT for a given part family.

  13. Research Techniques Made Simple: Emerging Methods to Elucidate Protein Interactions through Spatial Proximity.

    Science.gov (United States)

    Che, Yonglu; Khavari, Paul A

    2017-12-01

    Interactions between proteins are essential for fundamental cellular processes, and the diversity of such interactions enables the vast variety of functions essential for life. A persistent goal in biological research is to develop assays that can faithfully capture different types of protein interactions to allow their study. A major step forward in this direction came with a family of methods that delineates spatial proximity of proteins as an indirect measure of protein-protein interaction. A variety of enzyme- and DNA ligation-based methods measure protein co-localization in space, capturing novel interactions that were previously too transient or low affinity to be identified. Here we review some of the methods that have been successfully used to measure spatially proximal protein-protein interactions. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Mini Heme-Proteins: Designability of Structure and Diversity of Functions.

    Science.gov (United States)

    Rai, Jagdish

    2017-08-30

    Natural heme proteins may have heme bound to poly-peptide chain as a cofactor via noncovalent forces or heme as a prosthetic group may be covalently bound to the proteins. Nature has used porphyrins in diverse functions like electron transfer, oxidation, reduction, ligand binding, photosynthesis, signaling, etc. by modulating its properties through diverse protein matrices. Synthetic chemists have tried to utilize these molecules in equally diverse industrial and medical applications due to their versatile electro-chemical and optical properties. The heme iron has catalytic activity which can be modulated and enhanced for specific applications by protein matrix around it. Heme proteins can be designed into novel enzymes for sterio specific catalysis ranging from oxidation to reduction. These designed heme-proteins can have applications in industrial catalysis and biosensing. A peptide folds around heme easily due to hydrophobic effect of the large aromatic ring of heme. The directional property of co-ordinate bonding between peptide and metal ion in heme further specifies the structure. Therefore heme proteins can be easily designed for targeted structure and catalytic activity. The central aromatic chemical entity in heme viz. porphyrin is a very ancient molecule. Its presence in the prebiotic soup and in all forms of life suggests that it has played a vital role in the origin and progressive evolution of living organisms. Porphyrin macrocycles are highly conjugated systems composed of four modified pyrrole subunits interconnected at their α -carbon atoms via methine (=CH-) bridges. Initial minimalist models of hemoproteins focused on effect of heme-ligand co-ordinate bonding on chemical reactivity, spectroscopy, electrochemistry and magnetic properties of heme. The great sensitivity of these spectroscopic features of heme to its surrounding makes them extremely useful in structural elucidation of designed heme-peptide complexes. Therefore heme proteins are

  15. A Review of Research Methods in Children's Technology Design

    DEFF Research Database (Denmark)

    Jensen, Janne Jul; Skov, Mikael B.

    2005-01-01

    Research methods have been objects of discussions for dec-ades and defining research methods is still a quite substan-tial challenge. However, it is important to understand how research methods have been adapted in different disciplines as it potentially informs us on future directions and influ......-ences on the discipline. Inspired by previous studies from other disciplines, we conduct a survey of research methods in paper publications. 105 papers on children's technology design are classified on a two-dimensional matrix on research method and pur-pose. Our results show a strong focus on engineering of products...... as applied research and on evaluation of devel-oped products in the field or in the lab. Also, we find that much research is conducted in natural setting environments with strong focus on field studies....

  16. PL-PatchSurfer: a novel molecular local surface-based method for exploring protein-ligand interactions.

    Science.gov (United States)

    Hu, Bingjie; Zhu, Xiaolei; Monroe, Lyman; Bures, Mark G; Kihara, Daisuke

    2014-08-27

    Structure-based computational methods have been widely used in exploring protein-ligand interactions, including predicting the binding ligands of a given protein based on their structural complementarity. Compared to other protein and ligand representations, the advantages of a surface representation include reduced sensitivity to subtle changes in the pocket and ligand conformation and fast search speed. Here we developed a novel method named PL-PatchSurfer (Protein-Ligand PatchSurfer). PL-PatchSurfer represents the protein binding pocket and the ligand molecular surface as a combination of segmented surface patches. Each patch is characterized by its geometrical shape and the electrostatic potential, which are represented using the 3D Zernike descriptor (3DZD). We first tested PL-PatchSurfer on binding ligand prediction and found it outperformed the pocket-similarity based ligand prediction program. We then optimized the search algorithm of PL-PatchSurfer using the PDBbind dataset. Finally, we explored the utility of applying PL-PatchSurfer to a larger and more diverse dataset and showed that PL-PatchSurfer was able to provide a high early enrichment for most of the targets. To the best of our knowledge, PL-PatchSurfer is the first surface patch-based method that treats ligand complementarity at protein binding sites. We believe that using a surface patch approach to better understand protein-ligand interactions has the potential to significantly enhance the design of new ligands for a wide array of drug-targets.

  17. Tuning Parameters in Heuristics by Using Design of Experiments Methods

    Science.gov (United States)

    Arin, Arif; Rabadi, Ghaith; Unal, Resit

    2010-01-01

    With the growing complexity of today's large scale problems, it has become more difficult to find optimal solutions by using exact mathematical methods. The need to find near-optimal solutions in an acceptable time frame requires heuristic approaches. In many cases, however, most heuristics have several parameters that need to be "tuned" before they can reach good results. The problem then turns into "finding best parameter setting" for the heuristics to solve the problems efficiently and timely. One-Factor-At-a-Time (OFAT) approach for parameter tuning neglects the interactions between parameters. Design of Experiments (DOE) tools can be instead employed to tune the parameters more effectively. In this paper, we seek the best parameter setting for a Genetic Algorithm (GA) to solve the single machine total weighted tardiness problem in which n jobs must be scheduled on a single machine without preemption, and the objective is to minimize the total weighted tardiness. Benchmark instances for the problem are available in the literature. To fine tune the GA parameters in the most efficient way, we compare multiple DOE models including 2-level (2k ) full factorial design, orthogonal array design, central composite design, D-optimal design and signal-to-noise (SIN) ratios. In each DOE method, a mathematical model is created using regression analysis, and solved to obtain the best parameter setting. After verification runs using the tuned parameter setting, the preliminary results for optimal solutions of multiple instances were found efficiently.

  18. Novel TMS coils designed using an inverse boundary element method

    Science.gov (United States)

    Cobos Sánchez, Clemente; María Guerrero Rodriguez, Jose; Quirós Olozábal, Ángel; Blanco-Navarro, David

    2017-01-01

    In this work, a new method to design TMS coils is presented. It is based on the inclusion of the concept of stream function of a quasi-static electric current into a boundary element method. The proposed TMS coil design approach is a powerful technique to produce stimulators of arbitrary shape, and remarkably versatile as it permits the prototyping of many different performance requirements and constraints. To illustrate the power of this approach, it has been used for the design of TMS coils wound on rectangular flat, spherical and hemispherical surfaces, subjected to different constraints, such as minimum stored magnetic energy or power dissipation. The performances of such coils have been additionally described; and the torque experienced by each stimulator in the presence of a main magnetic static field have theoretically found in order to study the prospect of using them to perform TMS and fMRI concurrently. The obtained results show that described method is an efficient tool for the design of TMS stimulators, which can be applied to a wide range of coil geometries and performance requirements.

  19. THE METHOD OF DESIGNING ASSISTED ON COMPUTER OF THE

    Directory of Open Access Journals (Sweden)

    LUCA Cornelia

    2015-05-01

    Full Text Available To the base of the footwear soles designing, is the shoe last. The shoe lasts have irregular shapes, with various curves witch can’t be represented by a simple mathematic function. In order to design the footwear’s soles it’s necessary to take from the shoe last some base contours. These contours are obtained with high precision in a 3D CAD system. In the paper, it will be presented a method of designing of the soles for footwear, computer assisted. The copying process of the shoe last is done using the 3D digitizer. For digitizing, the shoe last spatial shape is positioned on the peripheral of data gathering, witch follows automatically the shoe last’s surface. The wire network obtained through digitizing is numerically interpolated with the interpolator functions in order to obtain the spatial numerical shape of the shoe last. The 3D designing of the sole will be realized on the numerical shape of the shoe last following the next steps: the manufacture of the sole’s surface, the lateral surface realization of the sole’s shape, obtaining the link surface between the lateral side and the planner one of the sole, of the sole’s margin, the sole’s designing contains the skid proof area. The main advantage of the designing method is the design precision, visualization in 3D space of the sole and the possibility to take the best decision viewing the acceptance of new sole’s pattern.

  20. A Testable Design Method for Memories by Boundary Scan Technique

    Directory of Open Access Journals (Sweden)

    Qiao Guo-Hui

    2016-01-01

    Full Text Available This paper presents a design for test the embedded flash in an object System-on-a-chip (SoC. The feature of the Flash TAP (Test Access Port complies with the IEEE std.1149.1, and it can select different scan chains and other control registers for other test. By the trade-off between the test time and the circuit area, an IST (In System Test circuit is designed in the SoC. Experiment results on the embedded memory have shown that the proposed method costs small testing timing by the use of IST.

  1. Design of A Cyclone Separator Using Approximation Method

    Science.gov (United States)

    Sin, Bong-Su; Choi, Ji-Won; Lee, Kwon-Hee

    2017-12-01

    A Separator is a device installed in industrial applications to separate mixed objects. The separator of interest in this research is a cyclone type, which is used to separate a steam-brine mixture in a geothermal plant. The most important performance of the cyclone separator is the collection efficiency. The collection efficiency in this study is predicted by performing the CFD (Computational Fluid Dynamics) analysis. This research defines six shape design variables to maximize the collection efficiency. Thus, the collection efficiency is set up as the objective function in optimization process. Since the CFD analysis requires a lot of calculation time, it is impossible to obtain the optimal solution by linking the gradient-based optimization algorithm. Thus, two approximation methods are introduced to obtain an optimum design. In this process, an L18 orthogonal array is adopted as a DOE method, and kriging interpolation method is adopted to generate the metamodel for the collection efficiency. Based on the 18 analysis results, the relative importance of each variable to the collection efficiency is obtained through the ANOVA (analysis of variance). The final design is suggested considering the results obtained from two optimization methods. The fluid flow analysis of the cyclone separator is conducted by using the commercial CFD software, ANSYS-CFX.

  2. A probabilistic design method for LMFBR fuel rods

    International Nuclear Information System (INIS)

    Peck, S.O.; Lovejoy, W.S.

    1977-01-01

    Fuel rod performance analyses for design purposes are dependent upon material properties, dimensions, and loads that are statistical in nature. Conventional design practice accounts for the uncertainties in relevant parameters by designing to a 'safety factor', set so as to assure safe operation. Arbitrary assignment of these safety factors, based upon a number of 'worst case' assumptions, may result in costly over-design. Probabilistic design methods provide a systematic way to reflect the uncertainties in design parameters. PECS-III is a computer code which employs Monte Carlo techniques to generate the probability density and distribution functions for time-to-failure and cumulative damage for sealed plenum LMFBR fuel rods on a single rod or whole core basis. In Monte Carlo analyses, a deterministic model (that maps single-valued inputs into single-valued outputs) is coupled to a statistical 'driver'. Uncertainties in the input are reflected by assigning probability densities to the input parameters. Dependent input variables are considered multivariate normal. Independent input variables may be arbitrarily distributed. Sample values are drawn from these input densities, and a complete analysis is done by the deterministic model to generate a sample point in the output distribution. This process is repeated many times, and the number of times each output value occurs is accumulated. The probability that some measure of rod performance will fall within given limits is estimated by the relative frequency with which the Monte Carlo samples fall within tho

  3. Tuning calcite morphology and growth acceleration by a rational design of highly stable protein-mimetics

    Science.gov (United States)

    Chen, Chun-Long; Qi, Jiahui; Tao, Jinhui; Zuckermann, Ronald N.; DeYoreo, James J.

    2014-01-01

    In nature, proteins play a significant role in biomineral formation. One of the ultimate goals of bioinspired materials science is to develop highly stable synthetic molecules that mimic the function of these natural proteins by controlling crystal formation. Here, we demonstrate that both the morphology and the degree of acceleration or inhibition observed during growth of calcite in the presence of peptoids can be rationally tuned by balancing the electrostatic and hydrophobic interactions, with hydrophobic interactions playing the dominant role. While either strong electrostatic or hydrophobic interactions inhibit growth and reduces expression of the {104} faces, correlations between peptoid-crystal binding energies and observed changes in calcite growth indicate moderate electrostatic interactions allow peptoids to weakly adsorb while moderate hydrophobic interactions cause disruption of surface-adsorbed water layers, leading to growth acceleration with retained expression of the {104} faces. This study provides fundamental principles for designing peptoids as crystallization promoters, and offers a straightforward screening method based on macroscopic crystal morphology. Because peptoids are sequence-specific, highly stable, and easily synthesized, peptoid-enhanced crystallization offers a broad range of potential applications. PMID:25189418

  4. Designing coarse grained-and atom based-potentials for protein-protein docking

    Directory of Open Access Journals (Sweden)

    Tobi Dror

    2010-11-01

    Full Text Available Abstract Background Protein-protein docking is a challenging computational problem in functional genomics, particularly when one or both proteins undergo conformational change(s upon binding. The major challenge is to define a scoring function soft enough to tolerate these changes and specific enough to distinguish between near-native and "misdocked" conformations. Results Using a linear programming (LP technique, we developed two types of potentials: (i Side chain-based and (ii Heavy atom-based. To achieve this we considered a set of 161 transient complexes and generated a large set of putative docked structures (decoys, based on a shape complementarity criterion, for each complex. The demand on the potentials was to yield, for the native (correctly docked structure, a potential energy lower than those of any of the non-native (misdocked structures. We show that the heavy atom-based potentials were able to comply with this requirement but not the side chain-based one. Thus, despite the smaller number of parameters, the capability of heavy atom-based potentials to discriminate between native and "misdocked" conformations is improved relative to those of the side chain-based potentials. The performance of the atom-based potentials was evaluated by a jackknife test on a set of 50 complexes taken from the Zdock2.3 decoys set. Conclusions Our results show that, using the LP approach, we were able to train our potentials using a dataset of transient complexes only the newly developed potentials outperform three other known potentials in this test.

  5. A Rapid Method for Determining the Concentration of Recombinant Protein Secreted from Pichia pastoris

    International Nuclear Information System (INIS)

    Sun, L W; Zhao, Y; Jiang, R; Song, Y; Feng, H; Feng, K; Niu, L P; Qi, C

    2011-01-01

    Pichia secretive expression system is one of powerful eukaryotic expression systems in genetic engineering, which is especially suitable for industrial utilization. Because of the low concentration of the target protein in initial experiment, the methods and conditions for expression of the target protein should be optimized according to the protein yield repetitively. It is necessary to set up a rapid, simple and convenient analysis method for protein expression levels instead of the generally used method such as ultrafiltration, purification, dialysis, lyophilization and so on. In this paper, acetone precipitation method was chosen to concentrate the recombinant protein firstly after comparing with four different protein precipitation methods systematically, and then the protein was analyzed by SDS-Polyacrylamide Gel Electrophoresis. The recombinant protein was determined with the feature of protein band by the Automated Image Capture and 1-D Analysis Software directly. With this method, the optimized expression conditions of basic fibroblast growth factor secreted from pichia were obtained, which is as the same as using traditional methods. Hence, a convenient tool to determine the optimized conditions for the expression of recombinant proteins in Pichia was established.

  6. Biocontainment of genetically modified organisms by synthetic protein design

    Science.gov (United States)

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

    2015-02-01

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

  7. Systems and methods for the secretion of recombinant proteins in gram negative bacteria

    Science.gov (United States)

    Withers, III, Sydnor T.; Dominguez, Miguel A; DeLisa, Matthew P.; Haitjema, Charles H.

    2016-08-09

    Disclosed herein are systems and methods for producing recombinant proteins utilizing mutant E. coli strains containing expression vectors carrying nucleic acids encoding the proteins, and secretory signal sequences to direct the secretion of the proteins to the culture medium. Host cells transformed with the expression vectors are also provided.

  8. Systems and methods for the secretion of recombinant proteins in gram negative bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Withers, III, Sydnor T.; Dominguez, Miguel A.; DeLisa, Matthew P.; Haitjema, Charles H.

    2017-02-21

    Disclosed herein are systems and methods for producing recombinant proteins utilizing mutant E. coli strains containing expression vectors carrying nucleic acids encoding the proteins, and secretory signal sequences to direct the secretion of the proteins to the culture medium. Host cells transformed with the expression vectors are also provided.

  9. The Folding of de Novo Designed Protein DS119 via Molecular Dynamics Simulations

    Directory of Open Access Journals (Sweden)

    Moye Wang

    2016-04-01

    Full Text Available As they are not subjected to natural selection process, de novo designed proteins usually fold in a manner different from natural proteins. Recently, a de novo designed mini-protein DS119, with a βαβ motif and 36 amino acids, has folded unusually slowly in experiments, and transient dimers have been detected in the folding process. Here, by means of all-atom replica exchange molecular dynamics (REMD simulations, several comparably stable intermediate states were observed on the folding free-energy landscape of DS119. Conventional molecular dynamics (CMD simulations showed that when two unfolded DS119 proteins bound together, most binding sites of dimeric aggregates were located at the N-terminal segment, especially residues 5–10, which were supposed to form β-sheet with its own C-terminal segment. Furthermore, a large percentage of individual proteins in the dimeric aggregates adopted conformations similar to those in the intermediate states observed in REMD simulations. These results indicate that, during the folding process, DS119 can easily become trapped in intermediate states. Then, with diffusion, a transient dimer would be formed and stabilized with the binding interface located at N-terminals. This means that it could not quickly fold to the native structure. The complicated folding manner of DS119 implies the important influence of natural selection on protein-folding kinetics, and more improvement should be achieved in rational protein design.

  10. Morphing methods to visualize coarse-grained protein dynamics.

    Science.gov (United States)

    Weiss, Dahlia R; Koehl, Patrice

    2014-01-01

    Morphing was initially developed as a cinematic effect, where one image is seamlessly transformed into another image. The technique was widely adopted by biologists to visualize the transition between protein conformational states, generating an interpolated pathway from an initial to a final protein structure. Geometric morphing seeks to create visually suggestive movies that illustrate structural changes between conformations but do not necessarily represent a biologically relevant pathway, while minimum energy path (MEP) interpolations aim at describing the true transition state between the crystal structure minima in the energy landscape.

  11. Design methods of Coanda effect nozzle with two streams

    Directory of Open Access Journals (Sweden)

    Michele TRANCOSSI

    2014-03-01

    Full Text Available This paper continues recent research of the authors about the ACHEON Coanda effect two streams nozzle. This nozzle aims to produce an effective deflection of a propulsive jet with a correspondent deviation of the thrust vector in a 2D plane. On the basis of a previously published mathematical model, based on integral equations, it tries to produce an effective design guideline, which can be adopted for design activities of the nozzle for aeronautic propulsion. The presented model allows defining a governing method for this innovative two stream synthetic jet nozzle. The uncertainness level of the model are discussed and novel aircraft architectures based on it are presented. A CFD validation campaign is produced focusing on validating the model and the designs produced.

  12. Developing an Engineering Design Process Assessment using Mixed Methods.

    Science.gov (United States)

    Wind, Stefanie A; Alemdar, Meltem; Lingle, Jeremy A; Gale, Jessica D; Moore, Roxanne A

    Recent reforms in science education worldwide include an emphasis on engineering design as a key component of student proficiency in the Science, Technology, Engineering, and Mathematics disciplines. However, relatively little attention has been directed to the development of psychometrically sound assessments for engineering. This study demonstrates the use of mixed methods to guide the development and revision of K-12 Engineering Design Process (EDP) assessment items. Using results from a middle-school EDP assessment, this study illustrates the combination of quantitative and qualitative techniques to inform item development and revisions. Overall conclusions suggest that the combination of quantitative and qualitative evidence provides an in-depth picture of item quality that can be used to inform the revision and development of EDP assessment items. Researchers and practitioners can use the methods illustrated here to gather validity evidence to support the interpretation and use of new and existing assessments.

  13. A novel design method for ground source heat pump

    Directory of Open Access Journals (Sweden)

    Dong Xing-Jie

    2014-01-01

    Full Text Available This paper proposes a novel design method for ground source heat pump. The ground source heat pump operation is controllable by using several parameters, such as the total meters of buried pipe, the space between wells, the thermal properties of soil, thermal resistance of the well, the initial temperature of soil, and annual dynamic load. By studying the effect of well number and well space, we conclude that with the increase of the well number, the inlet and outlet water temperatures decrease in summer and increase in winter, which enhance the efficiency of ground source heat pump. The well space slightly affects the water temperatures, but it affects the soil temperature to some extent. Also the ground source heat pump operations matching with cooling tower are investigated to achieve the thermal balance. This method greatly facilitates ground source heat pump design.

  14. The application of advanced rotor (performance) methods for design calculations

    Energy Technology Data Exchange (ETDEWEB)

    Bussel, G.J.W. van [Delft Univ. of Technology, Inst. for Wind Energy, Delft (Netherlands)

    1997-08-01

    The calculation of loads and performance of wind turbine rotors has been a topic for research over the last century. The principles for the calculation of loads on rotor blades with a given specific geometry, as well as the development of optimal shaped rotor blades have been published in the decades that significant aircraft development took place. Nowadays advanced computer codes are used for specific problems regarding modern aircraft, and application to wind turbine rotors has also been performed occasionally. The engineers designing rotor blades for wind turbines still use methods based upon global principles developed in the beginning of the century. The question what to expect in terms of the type of methods to be applied in a design environment for the near future is addressed here. (EG) 14 refs.

  15. Methods for validating the presence of and characterizing proteins deposited onto an array

    Science.gov (United States)

    Schabacker, Daniel S.

    2010-09-21

    A method of determining if proteins have been transferred from liquid-phase protein fractions to an array comprising staining the array with a total protein stain and imaging the array, optionally comparing the staining with a standard curve generated by staining known amounts of a known protein on the same or a similar array; a method of characterizing proteins transferred from liquid-phase protein fractions to an array including staining the array with a post-translational modification-specific (PTM-specific) stain and imaging the array and, optionally, after staining the array with a PTM-specific stain and imaging the array, washing the array, re-staining the array with a total protein stain, imaging the array, and comparing the imaging with the PTM-specific stain with the imaging with the total protein stain; stained arrays; and images of stained arrays.

  16. Applying Human-Centered Design Methods to Scientific Communication Products

    Science.gov (United States)

    Burkett, E. R.; Jayanty, N. K.; DeGroot, R. M.

    2016-12-01

    Knowing your users is a critical part of developing anything to be used or experienced by a human being. User interviews, journey maps, and personas are all techniques commonly employed in human-centered design practices because they have proven effective for informing the design of products and services that meet the needs of users. Many non-designers are unaware of the usefulness of personas and journey maps. Scientists who are interested in developing more effective products and communication can adopt and employ user-centered design approaches to better reach intended audiences. Journey mapping is a qualitative data-collection method that captures the story of a user's experience over time as related to the situation or product that requires development or improvement. Journey maps help define user expectations, where they are coming from, what they want to achieve, what questions they have, their challenges, and the gaps and opportunities that can be addressed by designing for them. A persona is a tool used to describe the goals and behavioral patterns of a subset of potential users or customers. The persona is a qualitative data model that takes the form of a character profile, built upon data about the behaviors and needs of multiple users. Gathering data directly from users avoids the risk of basing models on assumptions, which are often limited by misconceptions or gaps in understanding. Journey maps and user interviews together provide the data necessary to build the composite character that is the persona. Because a persona models the behaviors and needs of the target audience, it can then be used to make informed product design decisions. We share the methods and advantages of developing and using personas and journey maps to create more effective science communication products.

  17. Achieving integration in mixed methods designs-principles and practices.

    Science.gov (United States)

    Fetters, Michael D; Curry, Leslie A; Creswell, John W

    2013-12-01

    Mixed methods research offers powerful tools for investigating complex processes and systems in health and health care. This article describes integration principles and practices at three levels in mixed methods research and provides illustrative examples. Integration at the study design level occurs through three basic mixed method designs-exploratory sequential, explanatory sequential, and convergent-and through four advanced frameworks-multistage, intervention, case study, and participatory. Integration at the methods level occurs through four approaches. In connecting, one database links to the other through sampling. With building, one database informs the data collection approach of the other. When merging, the two databases are brought together for analysis. With embedding, data collection and analysis link at multiple points. Integration at the interpretation and reporting level occurs through narrative, data transformation, and joint display. The fit of integration describes the extent the qualitative and quantitative findings cohere. Understanding these principles and practices of integration can help health services researchers leverage the strengths of mixed methods. © Health Research and Educational Trust.

  18. Designing a mixed methods study in primary care.

    Science.gov (United States)

    Creswell, John W; Fetters, Michael D; Ivankova, Nataliya V

    2004-01-01

    Mixed methods or multimethod research holds potential for rigorous, methodologically sound investigations in primary care. The objective of this study was to use criteria from the literature to evaluate 5 mixed methods studies in primary care and to advance 3 models useful for designing such investigations. We first identified criteria from the social and behavioral sciences to analyze mixed methods studies in primary care research. We then used the criteria to evaluate 5 mixed methods investigations published in primary care research journals. Of the 5 studies analyzed, 3 included a rationale for mixing based on the need to develop a quantitative instrument from qualitative data or to converge information to best understand the research topic. Quantitative data collection involved structured interviews, observational checklists, and chart audits that were analyzed using descriptive and inferential statistical procedures. Qualitative data consisted of semistructured interviews and field observations that were analyzed using coding to develop themes and categories. The studies showed diverse forms of priority: equal priority, qualitative priority, and quantitative priority. Data collection involved quantitative and qualitative data gathered both concurrently and sequentially. The integration of the quantitative and qualitative data in these studies occurred between data analysis from one phase and data collection from a subsequent phase, while analyzing the data, and when reporting the results. We recommend instrument-building, triangulation, and data transformation models for mixed methods designs as useful frameworks to add rigor to investigations in primary care. We also discuss the limitations of our study and the need for future research.

  19. Medicinal Chemistry Projects Requiring Imaginative Structure-Based Drug Design Methods.

    Science.gov (United States)

    Moitessier, Nicolas; Pottel, Joshua; Therrien, Eric; Englebienne, Pablo; Liu, Zhaomin; Tomberg, Anna; Corbeil, Christopher R

    2016-09-20

    Computational methods for docking small molecules to proteins are prominent in drug discovery. There are hundreds, if not thousands, of documented examples-and several pertinent cases within our research program. Fifteen years ago, our first docking-guided drug design project yielded nanomolar metalloproteinase inhibitors and illustrated the potential of structure-based drug design. Subsequent applications of docking programs to the design of integrin antagonists, BACE-1 inhibitors, and aminoglycosides binding to bacterial RNA demonstrated that available docking programs needed significant improvement. At that time, docking programs primarily considered flexible ligands and rigid proteins. We demonstrated that accounting for protein flexibility, employing displaceable water molecules, and using ligand-based pharmacophores improved the docking accuracy of existing methods-enabling the design of bioactive molecules. The success prompted the development of our own program, Fitted, implementing all of these aspects. The primary motivation has always been to respond to the needs of drug design studies; the majority of the concepts behind the evolution of Fitted are rooted in medicinal chemistry projects and collaborations. Several examples follow: (1) Searching for HDAC inhibitors led us to develop methods considering drug-zinc coordination and its effect on the pKa of surrounding residues. (2) Targeting covalent prolyl oligopeptidase (POP) inhibitors prompted an update to Fitted to identify reactive groups and form bonds with a given residue (e.g., a catalytic residue) when the geometry allows it. Fitted-the first fully automated covalent docking program-was successfully applied to the discovery of four new classes of covalent POP inhibitors. As a result, efficient stereoselective syntheses of a few screening hits were prioritized rather than synthesizing large chemical libraries-yielding nanomolar inhibitors. (3) In order to study the metabolism of POP inhibitors by

  20. Fuel rod design by statistical methods for MOX fuel

    International Nuclear Information System (INIS)

    Heins, L.; Landskron, H.

    2000-01-01

    Statistical methods in fuel rod design have received more and more attention during the last years. One of different possible ways to use statistical methods in fuel rod design can be described as follows: Monte Carlo calculations are performed using the fuel rod code CARO. For each run with CARO, the set of input data is modified: parameters describing the design of the fuel rod (geometrical data, density etc.) and modeling parameters are randomly selected according to their individual distributions. Power histories are varied systematically in a way that each power history of the relevant core management calculation is represented in the Monte Carlo calculations with equal frequency. The frequency distributions of the results as rod internal pressure and cladding strain which are generated by the Monte Carlo calculation are evaluated and compared with the design criteria. Up to now, this methodology has been applied to licensing calculations for PWRs and BWRs, UO 2 and MOX fuel, in 3 countries. Especially for the insertion of MOX fuel resulting in power histories with relatively high linear heat generation rates at higher burnup, the statistical methodology is an appropriate approach to demonstrate the compliance of licensing requirements. (author)

  1. Numerical Verification Methods for Spherical $t$-Designs

    OpenAIRE

    Chen, Xiaojun

    2009-01-01

    The construction of spherical $t$-designs with $(t+1)^2$ points on the unit sphere $S^2$ in $\\mathbb{R}^3$ can be reformulated as an underdetermined system of nonlinear equations. This system is highly nonlinear and involves the evaluation of a degree $t$ polynomial in $(t+1)^4$ arguments. This paper reviews numerical verification methods using the Brouwer fixed point theorem and Krawczyk interval operator for solutions of the underdetermined system of nonlinear equations...

  2. Shielding design method for LMFBR validation on the Phenix factor

    International Nuclear Information System (INIS)

    Cabrillat, J.C.; Crouzet, J.; Misrakis, J.; Salvatores, M.; Rado, V.; Palmiotti, G.

    1983-05-01

    Shielding design methods, developed at CEA for shielding calculations find a global validation by the means of Phenix power reactor (250 MWe) measurements. Particularly, the secondary sodium activation of pool type LMFBR such as Super Phenix (1200 MWe) which is subject to strict safety limitation is well calculated by the adapted scheme, i.e. a two dimension transport calculation of shielding coupled to a Monte-Carlo calculation of secondary sodium activation

  3. Ultra-compact SWIR telephoto lens design with SMS method

    OpenAIRE

    Wang, Lin; Benitez Gimenez, Pablo; Miñano Dominguez, Juan Carlos; Infante Herrero, Jose Manuel; Fuente, Marta de la; Biot Marí, Guillermo

    2011-01-01

    In this work, we propose two new optical structures, using the Simultaneous Multiple Surfaces (SMS) method, comprised of 2 reflecting surfaces and 2 refracting surfaces, 800mm focal length, f/8 (aperture diameter 100 mm) and 1.18 0 diagonal field of view in the SWIR band. The lens surfaces are rotational symmetric and calculated to have good control of non-paraxial rays. We have achieved designs with excellent performance, and with total system length of less than 60 mm.

  4. comparison of protein extraction methods for the leaves of ficus

    African Journals Online (AJOL)

    F. I. Abdullah

    2017-05-01

    May 1, 2017 ... extraction technique is highly relied on the protein structure and its chemical characteristics. ..... EDTA, 1% Triton X 100, 80% glycerol, 1M DTT and distilled water) and vortexed ..... prot5438, doi : 10.1101/pdb.prot5438.

  5. Improving Machining Accuracy of CNC Machines with Innovative Design Methods

    Science.gov (United States)

    Yemelyanov, N. V.; Yemelyanova, I. V.; Zubenko, V. L.

    2018-03-01

    The article considers achieving the machining accuracy of CNC machines by applying innovative methods in modelling and design of machining systems, drives and machine processes. The topological method of analysis involves visualizing the system as matrices of block graphs with a varying degree of detail between the upper and lower hierarchy levels. This approach combines the advantages of graph theory and the efficiency of decomposition methods, it also has visual clarity, which is inherent in both topological models and structural matrices, as well as the resiliency of linear algebra as part of the matrix-based research. The focus of the study is on the design of automated machine workstations, systems, machines and units, which can be broken into interrelated parts and presented as algebraic, topological and set-theoretical models. Every model can be transformed into a model of another type, and, as a result, can be interpreted as a system of linear and non-linear equations which solutions determine the system parameters. This paper analyses the dynamic parameters of the 1716PF4 machine at the stages of design and exploitation. Having researched the impact of the system dynamics on the component quality, the authors have developed a range of practical recommendations which have enabled one to reduce considerably the amplitude of relative motion, exclude some resonance zones within the spindle speed range of 0...6000 min-1 and improve machining accuracy.

  6. A simple method for labelling proteins with 211At via diazotized aromatic diamine

    International Nuclear Information System (INIS)

    Wunderlich, G.; Franke, W.-G.; Fischer, S.; Dreyer, R.

    1987-01-01

    A simple and rapid method for labelling proteins with 211 At by means of a 1,4-diaminobenzene link is described. This link is transformed into the diazonium salt and subsequently reactions of both 211 At and proteins with the diazonium salt take place simultaneously. For possibly high yields of astatized protein an appropriate temperature of 273 K was found. The results demonstrate the difference between the reaction mechanisms of iodine and astatine with proteins. (author)

  7. Methods for the design and optimization of shaped tokamaks

    International Nuclear Information System (INIS)

    Haney, S.W.

    1988-05-01

    Two major questions associated with the design and optimization of shaped tokamaks are considered. How do physics and engineering constraints affect the design of shaped tokamaks? How can the process of designing shaped tokamaks be improved? The first question is addressed with the aid of a completely analytical procedure for optimizing the design of a resistive-magnet tokamak reactor. It is shown that physics constraints---particularly the MHD beta limits and the Murakami density limit---have an enormous, and sometimes, unexpected effect on the final design. The second question is addressed through the development of a series of computer models for calculating plasma equilibria, estimating poloidal field coil currents, and analyzing axisymmetric MHD stability in the presence of resistive conductors and feedback. The models offer potential advantages over conventional methods since they are characterized by extremely fast computer execution times, simplicity, and robustness. Furthermore, evidence is presented that suggests that very little loss of accuracy is required to achieve these desirable features. 94 refs., 66 figs., 14 tabs

  8. Normal mode analysis as a method to derive protein dynamics information from the Protein Data Bank.

    Science.gov (United States)

    Wako, Hiroshi; Endo, Shigeru

    2017-12-01

    Normal mode analysis (NMA) can facilitate quick and systematic investigation of protein dynamics using data from the Protein Data Bank (PDB). We developed an elastic network model-based NMA program using dihedral angles as independent variables. Compared to the NMA programs that use Cartesian coordinates as independent variables, key attributes of the proposed program are as follows: (1) chain connectivity related to the folding pattern of a polypeptide chain is naturally embedded in the model; (2) the full-atom system is acceptable, and owing to a considerably smaller number of independent variables, the PDB data can be used without further manipulation; (3) the number of variables can be easily reduced by some of the rotatable dihedral angles; (4) the PDB data for any molecule besides proteins can be considered without coarse-graining; and (5) individual motions of constituent subunits and ligand molecules can be easily decomposed into external and internal motions to examine their mutual and intrinsic motions. Its performance is illustrated with an example of a DNA-binding allosteric protein, a catabolite activator protein. In particular, the focus is on the conformational change upon cAMP and DNA binding, and on the communication between their binding sites remotely located from each other. In this illustration, NMA creates a vivid picture of the protein dynamics at various levels of the structures, i.e., atoms, residues, secondary structures, domains, subunits, and the complete system, including DNA and cAMP. Comparative studies of the specific protein in different states, e.g., apo- and holo-conformations, and free and complexed configurations, provide useful information for studying structurally and functionally important aspects of the protein.

  9. [Better performance of Western blotting: quick vs slow protein transfer, blotting membranes and the visualization methods].

    Science.gov (United States)

    Kong, Ling-Quan; Pu, Ying-Hui; Ma, Shi-Kun

    2008-01-01

    To study how the choices of the quick vs slow protein transfer, the blotting membranes and the visualization methods influence the performance of Western blotting. The cellular proteins were abstracted from human breast cell line MDA-MB-231 for analysis with Western blotting using quick (2 h) and slow (overnight) protein transfer, different blotting membranes (nitrocellulose, PVDF and nylon membranes) and different visualization methods (ECL and DAB). In Western blotting with slow and quick protein transfer, the prestained marker presented more distinct bands on nitrocellulose membrane than on the nylon and PVDF membranes, and the latter also showed clear bands on the back of the membrane to very likely cause confusion, which did not occur with nitrocellulose membrane. PVDF membrane allowed slightly clearer visualization of the proteins with DAB method as compared with nitrocellulose and nylon membranes, and on the latter two membranes, quick protein transfer was likely to result in somehow irregular bands in comparison with slow protein transfer. With slow protein transfer and chemiluminescence for visualization, all the 3 membranes showed clear background, while with quick protein transfer, nylon membrane gave rise to obvious background noise but the other two membranes did not. Different membranes should be selected for immunoblotting according to the actual needs of the experiment. Slow transfer of the proteins onto the membranes often has better effect than quick transfer, and enhanced chemiluminescence is superior to DAB for protein visualization and allows highly specific and sensitive analysis of the protein expressions.

  10. Rational design of highly potent HIV-1 fusion inhibitory proteins: Implication for developing antiviral therapeutics

    International Nuclear Information System (INIS)

    Ni Ling; Gao, George F.; Tien Po

    2005-01-01

    Recombinant protein containing one heptad-repeat 1 (HR1) segment and one HR2 segment of the HIV-1 gp41 (HR1-HR2) has been shown to fold into thermally stable six-helix bundle, representing the fusogenic core of gp41. In this study, we have used the fusogenic core as a scaffold to design HIV-1 fusion inhibitory proteins by linking another HR1 to the C terminus of HR1-HR2 (HR121) or additional HR2 to the N terminus of HR1-HR2 (HR212). Both recombinant proteins could be abundantly and solubly expressed and easily purified, exhibiting high stability and potent inhibitory activity on HIV-1 fusion with IC 50 values of 16.2 ± 2.8 and 2.8 ± 0.63 nM, respectively. These suggest that these rationally designed proteins can be further developed as novel anti-HIV-1 therapeutics

  11. Statistical methods in the mechanical design of fuel assemblies

    Energy Technology Data Exchange (ETDEWEB)

    Radsak, C.; Streit, D.; Muench, C.J. [AREVA NP GmbH, Erlangen (Germany)

    2013-07-01

    The mechanical design of a fuel assembly is still being mainly performed in a de terministic way. This conservative approach is however not suitable to provide a realistic quantification of the design margins with respect to licensing criter ia for more and more demanding operating conditions (power upgrades, burnup increase,..). This quantification can be provided by statistical methods utilizing all available information (e.g. from manufacturing, experience feedback etc.) of the topic under consideration. During optimization e.g. of the holddown system certain objectives in the mechanical design of a fuel assembly (FA) can contradict each other, such as sufficient holddown forces enough to prevent fuel assembly lift-off and reducing the holddown forces to minimize axial loads on the fuel assembly structure to ensure no negative effect on the control rod movement.By u sing a statistical method the fuel assembly design can be optimized much better with respect to these objectives than it would be possible based on a deterministic approach. This leads to a more realistic assessment and safer way of operating fuel assemblies. Statistical models are defined on the one hand by the quanti le that has to be maintained concerning the design limit requirements (e.g. one FA quantile) and on the other hand by the confidence level which has to be met. Using the above example of the holddown force, a feasible quantile can be define d based on the requirement that less than one fuel assembly (quantile > 192/19 3 [%] = 99.5 %) in the core violates the holddown force limit w ith a confidence of 95%. (orig.)

  12. Computational design of trimeric influenza-neutralizing proteins targeting the hemagglutinin receptor binding site

    Energy Technology Data Exchange (ETDEWEB)

    Strauch, Eva-Maria; Bernard, Steffen M.; La, David; Bohn, Alan J.; Lee, Peter S.; Anderson, Caitlin E.; Nieusma, Travis; Holstein, Carly A.; Garcia, Natalie K.; Hooper, Kathryn A.; Ravichandran, Rashmi; Nelson, Jorgen W.; Sheffler, William; Bloom, Jesse D.; Lee, Kelly K.; Ward, Andrew B.; Yager, Paul; Fuller, Deborah H.; Wilson, Ian A.; Baker , David (UWASH); (Scripps); (FHCRC)

    2017-06-12

    Many viral surface glycoproteins and cell surface receptors are homo-oligomers1, 2, 3, 4, and thus can potentially be targeted by geometrically matched homo-oligomers that engage all subunits simultaneously to attain high avidity and/or lock subunits together. The adaptive immune system cannot generally employ this strategy since the individual antibody binding sites are not arranged with appropriate geometry to simultaneously engage multiple sites in a single target homo-oligomer. We describe a general strategy for the computational design of homo-oligomeric protein assemblies with binding functionality precisely matched to homo-oligomeric target sites5, 6, 7, 8. In the first step, a small protein is designed that binds a single site on the target. In the second step, the designed protein is assembled into a homo-oligomer such that the designed binding sites are aligned with the target sites. We use this approach to design high-avidity trimeric proteins that bind influenza A hemagglutinin (HA) at its conserved receptor binding site. The designed trimers can both capture and detect HA in a paper-based diagnostic format, neutralizes influenza in cell culture, and completely protects mice when given as a single dose 24 h before or after challenge with influenza.

  13. An experimental design method leading to chemical Turing patterns.

    Science.gov (United States)

    Horváth, Judit; Szalai, István; De Kepper, Patrick

    2009-05-08

    Chemical reaction-diffusion patterns often serve as prototypes for pattern formation in living systems, but only two isothermal single-phase reaction systems have produced sustained stationary reaction-diffusion patterns so far. We designed an experimental method to search for additional systems on the basis of three steps: (i) generate spatial bistability by operating autoactivated reactions in open spatial reactors; (ii) use an independent negative-feedback species to produce spatiotemporal oscillations; and (iii) induce a space-scale separation of the activatory and inhibitory processes with a low-mobility complexing agent. We successfully applied this method to a hydrogen-ion autoactivated reaction, the thiourea-iodate-sulfite (TuIS) reaction, and noticeably produced stationary hexagonal arrays of spots and parallel stripes of pH patterns attributed to a Turing bifurcation. This method could be extended to biochemical reactions.

  14. A hybrid optimization method for biplanar transverse gradient coil design

    International Nuclear Information System (INIS)

    Qi Feng; Tang Xin; Jin Zhe; Jiang Zhongde; Shen Yifei; Meng Bin; Zu Donglin; Wang Weimin

    2007-01-01

    The optimization of transverse gradient coils is one of the fundamental problems in designing magnetic resonance imaging gradient systems. A new approach is presented in this paper to optimize the transverse gradient coils' performance. First, in the traditional spherical harmonic target field method, high order coefficients, which are commonly ignored, are used in the first stage of the optimization process to give better homogeneity. Then, some cosine terms are introduced into the series expansion of stream function. These new terms provide simulated annealing optimization with new freedoms. Comparison between the traditional method and the optimized method shows that the inhomogeneity in the region of interest can be reduced from 5.03% to 1.39%, the coil efficiency increased from 3.83 to 6.31 mT m -1 A -1 and the minimum distance of these discrete coils raised from 1.54 to 3.16 mm

  15. Guidance for using mixed methods design in nursing practice research.

    Science.gov (United States)

    Chiang-Hanisko, Lenny; Newman, David; Dyess, Susan; Piyakong, Duangporn; Liehr, Patricia

    2016-08-01

    The mixed methods approach purposefully combines both quantitative and qualitative techniques, enabling a multi-faceted understanding of nursing phenomena. The purpose of this article is to introduce three mixed methods designs (parallel; sequential; conversion) and highlight interpretive processes that occur with the synthesis of qualitative and quantitative findings. Real world examples of research studies conducted by the authors will demonstrate the processes leading to the merger of data. The examples include: research questions; data collection procedures and analysis with a focus on synthesizing findings. Based on experience with mixed methods studied, the authors introduce two synthesis patterns (complementary; contrasting), considering application for practice and implications for research. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Salt-bridge networks within globular and disordered proteins: characterizing trends for designable interactions.

    Science.gov (United States)

    Basu, Sankar; Mukharjee, Debasish

    2017-07-01

    There has been considerable debate about the contribution of salt bridges to the stabilization of protein folds, in spite of their participation in crucial protein functions. Salt bridges appear to contribute to the activity-stability trade-off within proteins by bringing high-entropy charged amino acids into close contacts during the course of their functions. The current study analyzes the modes of association of salt bridges (in terms of networks) within globular proteins and at protein-protein interfaces. While the most common and trivial type of salt bridge is the isolated salt bridge, bifurcated salt bridge appears to be a distinct salt-bridge motif having a special topology and geometry. Bifurcated salt bridges are found ubiquitously in proteins and interprotein complexes. Interesting and attractive examples presenting different modes of interaction are highlighted. Bifurcated salt bridges appear to function as molecular clips that are used to stitch together large surface contours at interacting protein interfaces. The present work also emphasizes the key role of salt-bridge-mediated interactions in the partial folding of proteins containing long stretches of disordered regions. Salt-bridge-mediated interactions seem to be pivotal to the promotion of "disorder-to-order" transitions in small disordered protein fragments and their stabilization upon binding. The results obtained in this work should help to guide efforts to elucidate the modus operandi of these partially disordered proteins, and to conceptualize how these proteins manage to maintain the required amount of disorder even in their bound forms. This work could also potentially facilitate explorations of geometrically specific designable salt bridges through the characterization of composite salt-bridge networks. Graphical abstract ᅟ.

  17. Metal binding proteins, recombinant host cells and methods

    Science.gov (United States)

    Summers, Anne O.; Caguiat, Jonathan J.

    2004-06-15

    The present disclosure provides artificial heavy metal binding proteins termed chelons by the inventors. These chelons bind cadmium and/or mercuric ions with relatively high affinity. Also disclosed are coding sequences, recombinant DNA molecules and recombinant host cells comprising those recombinant DNA molecules for expression of the chelon proteins. In the recombinant host cells or transgenic plants, the chelons can be used to bind heavy metals taken up from contaminated soil, groundwater or irrigation water and to concentrate and sequester those ions. Recombinant enteric bacteria can be used within the gastrointestinal tracts of animals or humans exposed to toxic metal ions such as mercury and/or cadmium, where the chelon recombinantly expressed in chosen in accordance with the ion to be rededicated. Alternatively, the chelons can be immobilized to solid supports to bind and concentrate heavy metals from a contaminated aqueous medium including biological fluids.

  18. Simplified Method for Predicting a Functional Class of Proteins in Transcription Factor Complexes

    KAUST Repository

    Piatek, Marek J.

    2013-07-12

    Background:Initiation of transcription is essential for most of the cellular responses to environmental conditions and for cell and tissue specificity. This process is regulated through numerous proteins, their ligands and mutual interactions, as well as interactions with DNA. The key such regulatory proteins are transcription factors (TFs) and transcription co-factors (TcoFs). TcoFs are important since they modulate the transcription initiation process through interaction with TFs. In eukaryotes, transcription requires that TFs form different protein complexes with various nuclear proteins. To better understand transcription regulation, it is important to know the functional class of proteins interacting with TFs during transcription initiation. Such information is not fully available, since not all proteins that act as TFs or TcoFs are yet annotated as such, due to generally partial functional annotation of proteins. In this study we have developed a method to predict, using only sequence composition of the interacting proteins, the functional class of human TF binding partners to be (i) TF, (ii) TcoF, or (iii) other nuclear protein. This allows for complementing the annotation of the currently known pool of nuclear proteins. Since only the knowledge of protein sequences is required in addition to protein interaction, the method should be easily applicable to many species.Results:Based on experimentally validated interactions between human TFs with different TFs, TcoFs and other nuclear proteins, our two classification systems (implemented as a web-based application) achieve high accuracies in distinguishing TFs and TcoFs from other nuclear proteins, and TFs from TcoFs respectively.Conclusion:As demonstrated, given the fact that two proteins are capable of forming direct physical interactions and using only information about their sequence composition, we have developed a completely new method for predicting a functional class of TF interacting protein partners

  19. Analysis of proteins and peptides by electromigration methods in microchips

    Czech Academy of Sciences Publication Activity Database

    Štěpánová, Sille; Kašička, Václav

    2017-01-01

    Roč. 40, č. 1 (2017), s. 228-250 ISSN 1615-9306 R&D Projects: GA ČR(CZ) GA15-01948S Institutional support: RVO:61388963 Keywords : microchip electrophoresis * microfluidics * peptides * proteins Subject RIV: CB - Analytical Chemistry, Separation OBOR OECD: Analytical chemistry Impact factor: 2.557, year: 2016 http://onlinelibrary.wiley.com/doi/10.1002/jssc.201600962/full

  20. Tracking of protein folding by chiral spectroscopic methods

    Czech Academy of Sciences Publication Activity Database

    Krupová, Monika; Andrushchenko, Valery; Bouř, Petr

    2016-01-01

    Roč. 23, č. 1 (2016), s. 36 ISSN 1211-5894. [Discussions in Structural Molecular Biology /14./. 17.03.2016-19.03.2016, Nové Hrady] R&D Projects: GA ČR(CZ) GA16-04902S; GA ČR GA15-09072S Institutional support: RVO:61388963 Keywords : proteins * fibrils * lanthanides * vibrational circular dichroism * circularly polarised luminescence Subject RIV: CF - Physical ; Theoretical Chemistry

  1. Formulation of probabilistic models of protein structure in atomic detail using the reference ratio method

    DEFF Research Database (Denmark)

    Valentin, Jan B.; Andreetta, Christian; Boomsma, Wouter

    2014-01-01

    We propose a method to formulate probabilistic models of protein structure in atomic detail, for a given amino acid sequence, based on Bayesian principles, while retaining a close link to physics. We start from two previously developed probabilistic models of protein structure on a local length s....... The results indicate that the proposed method and the probabilistic models show considerable promise for probabilistic protein structure prediction and related applications. © 2013 Wiley Periodicals, Inc....

  2. ProtaBank: A repository for protein design and engineering data.

    Science.gov (United States)

    Wang, Connie Y; Chang, Paul M; Ary, Marie L; Allen, Benjamin D; Chica, Roberto A; Mayo, Stephen L; Olafson, Barry D

    2018-03-25

    We present ProtaBank, a repository for storing, querying, analyzing, and sharing protein design and engineering data in an actively maintained and updated database. ProtaBank provides a format to describe and compare all types of protein mutational data, spanning a wide range of properties and techniques. It features a user-friendly web interface and programming layer that streamlines data deposition and allows for batch input and queries. The database schema design incorporates a standard format for reporting protein sequences and experimental data that facilitates comparison of results across different data sets. A suite of analysis and visualization tools are provided to facilitate discovery, to guide future designs, and to benchmark and train new predictive tools and algorithms. ProtaBank will provide a valuable resource to the protein engineering community by storing and safeguarding newly generated data, allowing for fast searching and identification of relevant data from the existing literature, and exploring correlations between disparate data sets. ProtaBank invites researchers to contribute data to the database to make it accessible for search and analysis. ProtaBank is available at https://protabank.org. © 2018 The Authors Protein Science published by Wiley Periodicals, Inc. on behalf of The Protein Society.

  3. A scalable and accurate method for classifying protein-ligand binding geometries using a MapReduce approach.

    Science.gov (United States)

    Estrada, T; Zhang, B; Cicotti, P; Armen, R S; Taufer, M

    2012-07-01

    We present a scalable and accurate method for classifying protein-ligand binding geometries in molecular docking. Our method is a three-step process: the first step encodes the geometry of a three-dimensional (3D) ligand conformation into a single 3D point in the space; the second step builds an octree by assigning an octant identifier to every single point in the space under consideration; and the third step performs an octree-based clustering on the reduced conformation space and identifies the most dense octant. We adapt our method for MapReduce and implement it in Hadoop. The load-balancing, fault-tolerance, and scalability in MapReduce allow screening of very large conformation spaces not approachable with traditional clustering methods. We analyze results for docking trials for 23 protein-ligand complexes for HIV protease, 21 protein-ligand complexes for Trypsin, and 12 protein-ligand complexes for P38alpha kinase. We also analyze cross docking trials for 24 ligands, each docking into 24 protein conformations of the HIV protease, and receptor ensemble docking trials for 24 ligands, each docking in a pool of HIV protease receptors. Our method demonstrates significant improvement over energy-only scoring for the accurate identification of native ligand geometries in all these docking assessments. The advantages of our clustering approach make it attractive for complex applications in real-world drug design efforts. We demonstrate that our method is particularly useful for clustering docking results using a minimal ensemble of representative protein conformational states (receptor ensemble docking), which is now a common strategy to address protein flexibility in molecular docking. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Designing A Mixed Methods Study In Primary Care

    Science.gov (United States)

    Creswell, John W.; Fetters, Michael D.; Ivankova, Nataliya V.

    2004-01-01

    BACKGROUND Mixed methods or multimethod research holds potential for rigorous, methodologically sound investigations in primary care. The objective of this study was to use criteria from the literature to evaluate 5 mixed methods studies in primary care and to advance 3 models useful for designing such investigations. METHODS We first identified criteria from the social and behavioral sciences to analyze mixed methods studies in primary care research. We then used the criteria to evaluate 5 mixed methods investigations published in primary care research journals. RESULTS Of the 5 studies analyzed, 3 included a rationale for mixing based on the need to develop a quantitative instrument from qualitative data or to converge information to best understand the research topic. Quantitative data collection involved structured interviews, observational checklists, and chart audits that were analyzed using descriptive and inferential statistical procedures. Qualitative data consisted of semistructured interviews and field observations that were analyzed using coding to develop themes and categories. The studies showed diverse forms of priority: equal priority, qualitative priority, and quantitative priority. Data collection involved quantitative and qualitative data gathered both concurrently and sequentially. The integration of the quantitative and qualitative data in these studies occurred between data analysis from one phase and data collection from a subsequent phase, while analyzing the data, and when reporting the results. DISCUSSION We recommend instrument-building, triangulation, and data transformation models for mixed methods designs as useful frameworks to add rigor to investigations in primary care. We also discuss the limitations of our study and the need for future research. PMID:15053277

  5. Forming a method mindset: The role of knowledge and preference in facilitating heuristic method usage in design

    DEFF Research Database (Denmark)

    Daalhuizen, Jaap; Person, Oscar; Gattol, Valentin

    2013-01-01

    Both systematic and heuristic methods are common practice when designing. Yet, in teaching students how to design, heuristic methods are typically only granted a secondary role. So, how do designers and students develop a mindset for using heuristic methods? In this paper, we study how prior...... knowledge (about heuristic methods and their usage) and preference (for using heuristic methods) relate to the reported use of heuristic methods when designing. Drawing on a survey among 304 students enrolled in a master-level course on design theory and methodology, we investigated method usage for five...... indirectly influenced method usage through a 'complementary' mediation of method preference....

  6. Method for determining the concentration of adsorbed protein and cell biomass in cellulose fermentations

    Energy Technology Data Exchange (ETDEWEB)

    Moreira, A R; Phillips, J A; Humphrey, A E

    1978-09-01

    The method presented is based on the determination of the total Lowry protein of the solids and the total Kjeldahl nitrogen of the solids. Experimental data proving the validity of the method are reported. (JSR)

  7. Methods for promoting wound healing and muscle regeneration with the cell signaling protein nell1

    Energy Technology Data Exchange (ETDEWEB)

    Culiat, Cymbeline T.

    2018-03-20

    The present invention provides methods for promoting wound healing and treating muscle atrophy in a mammal in need. The method comprises administering to the mammal a Nell1 protein or a Nell1 nucleic acid molecule.

  8. Serum protein profile of Malaria patients through SDS-PAGE method ...

    African Journals Online (AJOL)

    Serum protein profile of Malaria patients through SDS-PAGE method. ... reliable method in the diagnosis of antibodies produced against Plasmodium spps. ... of malaria patients may be undertaken for study to develop possible future vaccine.

  9. Methods for promoting wound healing and muscle regeneration with the cell signaling protein Nell1

    Science.gov (United States)

    Culiat, Cymbeline T [Oak Ridge, TN

    2011-03-22

    The present invention provides methods for promoting wound healing and treating muscle atrophy in a mammal in need. The method comprises administering to the mammal a Nell1 protein or a Nell1 nucleic acid molecule.

  10. A NEW DESIGN METHOD FOR FLAT FOOTWEAR SOLES

    Directory of Open Access Journals (Sweden)

    IONESCU Cozmin

    2016-05-01

    Full Text Available Carried research regarding footwear soles reveald that by moulding footwear details can be obtained in a wide variety of models. Shoe soles are complex three dimensional objects and for attaching them with the uppers, the interor countour of the soles has to correspond to the featherline contour of the last. That’s why, is necessary that soles design to be done with high accuracy and in strict accordance to the last. Nowadays, there are specialized software applications which can perform various computer aided design processes for footwear. Among the high performance systems used for the design of footwear soles and injection moulds for shoe soles, we may mention: Delcam Shoe Solution, Delcam PowerSHAPE-e, Padsy II and Padsy III, Shoe Master System, Lectra System, Parmel System and ATOS II System. This paper presents a 3D design method, developed by the authors, for footwear flat soles using PowerSHAPE-e software programm from of Delcam Crispin. The computer-aided design technique used in this paper highlights several important advantages that include: increased design quality; three dimensional viewing of soles, which can lead to immediate decisions, regarding the acceptance of newly developed models; it can be appreciated the complexity of mould cavities execution, without the need of making prototypes; the outlines of construction templates are accurately obtained for the mould cavities and for all size numbers; calculations can easily be done for determining the soles volume for the entire size number, with implications on estimating polymer blend consumption and so on.

  11. Design of time interval generator based on hybrid counting method

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Yuan [State Key Laboratory of Particle Detection and Electronics, University of Science and Technology of China, Hefei, Anhui 230026 (China); Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); Wang, Zhaoqi [State Key Laboratory of Particle Detection and Electronics, University of Science and Technology of China, Hefei, Anhui 230026 (China); Lu, Houbing [State Key Laboratory of Particle Detection and Electronics, University of Science and Technology of China, Hefei, Anhui 230026 (China); Hefei Electronic Engineering Institute, Hefei 230037 (China); Chen, Lian [State Key Laboratory of Particle Detection and Electronics, University of Science and Technology of China, Hefei, Anhui 230026 (China); Jin, Ge, E-mail: goldjin@ustc.edu.cn [State Key Laboratory of Particle Detection and Electronics, University of Science and Technology of China, Hefei, Anhui 230026 (China)

    2016-10-01

    Time Interval Generators (TIGs) are frequently used for the characterizations or timing operations of instruments in particle physics experiments. Though some “off-the-shelf” TIGs can be employed, the necessity of a custom test system or control system makes the TIGs, being implemented in a programmable device desirable. Nowadays, the feasibility of using Field Programmable Gate Arrays (FPGAs) to implement particle physics instrumentation has been validated in the design of Time-to-Digital Converters (TDCs) for precise time measurement. The FPGA-TDC technique is based on the architectures of Tapped Delay Line (TDL), whose delay cells are down to few tens of picosecond. In this case, FPGA-based TIGs with high delay step are preferable allowing the implementation of customized particle physics instrumentations and other utilities on the same FPGA device. A hybrid counting method for designing TIGs with both high resolution and wide range is presented in this paper. The combination of two different counting methods realizing an integratable TIG is described in detail. A specially designed multiplexer for tap selection is emphatically introduced. The special structure of the multiplexer is devised for minimizing the different additional delays caused by the unpredictable routings from different taps to the output. A Kintex-7 FPGA is used for the hybrid counting-based implementation of a TIG, providing a resolution up to 11 ps and an interval range up to 8 s.

  12. Design of time interval generator based on hybrid counting method

    International Nuclear Information System (INIS)

    Yao, Yuan; Wang, Zhaoqi; Lu, Houbing; Chen, Lian; Jin, Ge

    2016-01-01

    Time Interval Generators (TIGs) are frequently used for the characterizations or timing operations of instruments in particle physics experiments. Though some “off-the-shelf” TIGs can be employed, the necessity of a custom test system or control system makes the TIGs, being implemented in a programmable device desirable. Nowadays, the feasibility of using Field Programmable Gate Arrays (FPGAs) to implement particle physics instrumentation has been validated in the design of Time-to-Digital Converters (TDCs) for precise time measurement. The FPGA-TDC technique is based on the architectures of Tapped Delay Line (TDL), whose delay cells are down to few tens of picosecond. In this case, FPGA-based TIGs with high delay step are preferable allowing the implementation of customized particle physics instrumentations and other utilities on the same FPGA device. A hybrid counting method for designing TIGs with both high resolution and wide range is presented in this paper. The combination of two different counting methods realizing an integratable TIG is described in detail. A specially designed multiplexer for tap selection is emphatically introduced. The special structure of the multiplexer is devised for minimizing the different additional delays caused by the unpredictable routings from different taps to the output. A Kintex-7 FPGA is used for the hybrid counting-based implementation of a TIG, providing a resolution up to 11 ps and an interval range up to 8 s.

  13. Designation and verification of road markings detection and guidance method

    Science.gov (United States)

    Wang, Runze; Jian, Yabin; Li, Xiyuan; Shang, Yonghong; Wang, Jing; Zhang, JingChuan

    2018-01-01

    With the rapid development of China's space industry, digitization and intelligent is the tendency of the future. This report is present a foundation research about guidance system which based on the HSV color space. With the help of these research which will help to design the automatic navigation and parking system for the frock transport car and the infrared lamp homogeneity intelligent test equipment. The drive mode, steer mode as well as the navigation method was selected. In consideration of the practicability, it was determined to use the front-wheel-steering chassis. The steering mechanism was controlled by the stepping motors, and it is guided by Machine Vision. The optimization and calibration of the steering mechanism was made. A mathematical model was built and the objective functions was constructed for the steering mechanism. The extraction method of the steering line was studied and the motion controller was designed and optimized. The theory of HSV, RGB color space and analysis of the testing result will be discussed Using the function library OPENCV on the Linux system to fulfill the camera calibration. Based on the HSV color space to design the guidance algorithm.

  14. Centrifugal compressor shape modification using a proposed inverse design method

    International Nuclear Information System (INIS)

    Niliahmadabadi, Mahdi; Poursadegh, Farzad

    2013-01-01

    This paper is concerned with a quasi-3D design method for the radial and axial diffusers of a centrifugal compressor on the meridional plane. The method integrates a novel inverse design algorithm, called ball-spine algorithm (BSA), and a quasi-3D analysis code. The Euler equation is solved on the meridional plane for a numerical domain, of which unknown boundaries (hub and shroud) are iteratively modified under the BSA until a prescribed pressure distribution is reached. In BSA, unknown walls are composed of a set of virtual balls that move freely along specified directions called spines. The difference between target and current pressure distributions causes the flexible boundary to deform at each modification step. In validating the quasi-3D analysis code, a full 3D Navier-Stokes code is used to analyze the existing and designed compressors numerically. Comparison of the quasi-3D analysis results with full 3D analysis results shows viable agreement. The 3D numerical analysis of the current compressor shows a huge total pressure loss on the 90 .deg. bend between the radial and axial diffusers. Geometric modification of the meridional plane causes the efficiency to improve by about 10%.

  15. Task-Based Method for Designing Underactuated Mechanisms

    Directory of Open Access Journals (Sweden)

    Shoichiro Kamada

    2012-03-01

    Full Text Available In this paper we introduce a task-based method for designing underactuated multi-joint prosthetic hands for specific grasping tasks. The designed robotic hands or prosthetic hands contain fewer independent actuators than joints. We chose a few specific grasping tasks that are frequently repeated in everyday life and analysed joint motions of the hand during the completion of each task and the level of participation of each joint. The information was used for the synthesis of dedicated underactuated mechanisms that can operate in a low dimensional task coordinate space. We propose two methods for reducing the actuators' number. The kinematic parameters of the synthesized mechanism are determined by using a numerical approach. In this study the joint angles of the synthesized hand are considered as linearly dependent on the displacements of the actuators. We introduced a special error index that allowed us to compare the original trajectory and the trajectory performed by the synthesized mechanism, and to select the kinematic parameters of the new kinematic structure as a way to reduce the error. The approach allows the design of simple gripper mechanisms with good accuracy for the preliminary defined tasks.

  16. Centrifugal compressor shape modification using a proposed inverse design method

    Energy Technology Data Exchange (ETDEWEB)

    Niliahmadabadi, Mahdi [Isfahan University of Technology, Isfahan (Iran, Islamic Republic of); Poursadegh, Farzad [Sharif University of Technology, Tehran (Iran, Islamic Republic of)

    2013-03-15

    This paper is concerned with a quasi-3D design method for the radial and axial diffusers of a centrifugal compressor on the meridional plane. The method integrates a novel inverse design algorithm, called ball-spine algorithm (BSA), and a quasi-3D analysis code. The Euler equation is solved on the meridional plane for a numerical domain, of which unknown boundaries (hub and shroud) are iteratively modified under the BSA until a prescribed pressure distribution is reached. In BSA, unknown walls are composed of a set of virtual balls that move freely along specified directions called spines. The difference between target and current pressure distributions causes the flexible boundary to deform at each modification step. In validating the quasi-3D analysis code, a full 3D Navier-Stokes code is used to analyze the existing and designed compressors numerically. Comparison of the quasi-3D analysis results with full 3D analysis results shows viable agreement. The 3D numerical analysis of the current compressor shows a huge total pressure loss on the 90 .deg. bend between the radial and axial diffusers. Geometric modification of the meridional plane causes the efficiency to improve by about 10%.

  17. A simple immunoblotting method after separation of proteins in agarose gel

    DEFF Research Database (Denmark)

    Koch, C; Skjødt, K; Laursen, I

    1985-01-01

    A simple and sensitive method for immunoblotting of proteins after separation in agarose gels is described. It involves transfer of proteins onto nitrocellulose paper simply by diffusion through pressure, a transfer which only takes about 10 min. By this method we have demonstrated the existence ...

  18. Discrete method for design of flow distribution in manifolds

    International Nuclear Information System (INIS)

    Wang, Junye; Wang, Hualin

    2015-01-01

    Flow in manifold systems is encountered in designs of various industrial processes, such as fuel cells, microreactors, microchannels, plate heat exchanger, and radial flow reactors. The uniformity of flow distribution in manifold is a key indicator for performance of the process equipment. In this paper, a discrete method for a U-type arrangement was developed to evaluate the uniformity of the flow distribution and the pressure drop and then was used for direct comparisons between the U-type and the Z-type. The uniformity of the U-type is generally better than that of the Z-type in most of cases for small ζ and large M. The U-type and the Z-type approach each other as ζ increases or M decreases. However, the Z-type is more sensitive to structures than the U-type and approaches uniform flow distribution faster than the U-type as M decreases or ζ increases. This provides a simple yet powerful tool for the designers to evaluate and select a flow arrangement and offers practical measures for industrial applications. - Highlights: • Discrete methodology of flow field designs in manifolds with U-type arrangements. • Quantitative comparison between U-type and Z-type arrangements. • Discrete solution of flow distribution with varying flow coefficients. • Practical measures and guideline to design of manifold systems.

  19. Comparison of new immunofluorescence method for detection of soy protein in meat products with immunohistochemical, histochemical, and ELISA methods

    Directory of Open Access Journals (Sweden)

    Michaela Petrášová

    2014-01-01

    Full Text Available Soy proteins are commonly used in the food industry thanks to their technological properties. However, soy is, along with cow’s milk, eggs, wheat, peanuts, tree nuts, fish, crustaceans, and molluscs, responsible for around 90% of food allergies, and is also one of the foodstuffs that can cause anaphylaxis. The aim of this work was to compare the immunofluorescence method for the detection of soy protein in meat products purchased from the retail market with other microscopic methods (immunohistochemical and histochemical, with the ELISA reference method and with the confirmatory results. Within the research, 127 meat products purchased in the retail network were examined using the immunofluorescence method used for the detection of soy protein. The method was compared to Enzyme-Linked ImmunoSorbent Assay (ELISA, immunohistochemical, and histochemical methods. According to McNemar’s test, non-compliance between the immunofluorescence method and immunohistochemical method was low. In addition, a significant difference between the fluorescence method and ELISA (P P < 0.01 was found. The immunofluorescence method was also compared with confirmatory results. According to McNemar’s test, non-compliance between the immunofluorescence method and confirmatory results was low. The results showed the possibilities of this new method to detect the content of soy protein in meat products.

  20. Measuring Protein Synthesis Rate In Living Object Using Flooding Dose And Constant Infusion Methods

    OpenAIRE

    Ulyarti, Ulyarti

    2018-01-01

    Constant infusion is a method used for measuring protein synthesis rate in living object which uses low concentration of amino acid tracers. Flooding dose method is another technique used to measure the rate of protein synthesis which uses labelled amino acid together with large amount of unlabelled amino acid.  The latter method was firstly developed to solve the problem in determination of precursor pool arise from constant infusion method.  The objective of this writing is to com...