Recombinant and epitope-based vaccines on the road to the market and implications for vaccine design and production.

PubMed

Oyarzún, Patricio; Kobe, Bostjan

2016-03-03

Novel vaccination approaches based on rational design of B- and T-cell epitopes - epitope-based vaccines - are making progress in the clinical trial pipeline. The epitope-focused recombinant protein-based malaria vaccine (termed RTS,S) is a next-generation approach that successfully reached phase-III trials, and will potentially become the first commercial vaccine against a human parasitic disease. Progress made on methods such as recombinant DNA technology, advanced cell-culture techniques, immunoinformatics and rational design of immunogens are driving the development of these novel concepts. Synthetic recombinant proteins comprising both B- and T-cell epitopes can be efficiently produced through modern biotechnology and bioprocessing methods, and can enable the induction of large repertoires of immune specificities. In particular, the inclusion of appropriate CD4+ T-cell epitopes is increasingly considered a key vaccine component to elicit robust immune responses, as suggested by results coming from HIV-1 clinical trials. In silico strategies for vaccine design are under active development to address genetic variation in pathogens and several broadly protective "universal" influenza and HIV-1 vaccines are currently at different stages of clinical trials. Other methods focus on improving population coverage in target populations by rationally considering specificity and prevalence of the HLA proteins, though a proof-of-concept in humans has not been demonstrated yet. Overall, we expect immunoinformatics and bioprocessing methods to become a central part of the next-generation epitope-based vaccine development and production process.

Structural optimization of large ocean-going structures

NASA Technical Reports Server (NTRS)

Hughes, O. F.

1984-01-01

Ocean-going vehicles and platforms are among the largest structures in the world and are subjected to relatively harsh conditions of motions and loads. Some of them, such as semi-submersible platforms, are a relatively new type of structure and hence there is no formal, well evolved and established structural design code as there is for more traditional structures. More recently, efforts have also been made to develop a design method of this type for ships and other ocean structures. One of the many advantages of a rationally based design method is versatility; it can be used for structures that have widely differing purposes, measures of merit, shapes and sizes. The purpose is to describe a rationally based design method that has been developed within the field of ocean structures, in order that persons dealing with other types of structure can judge whether and to what extent its various features may be useful for those other types. Also, even though some features may not be applicable they might stimulate some useful ideas.

Rationally reduced libraries for combinatorial pathway optimization minimizing experimental effort.

PubMed

Jeschek, Markus; Gerngross, Daniel; Panke, Sven

2016-03-31

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

Precise Composition Tailoring of Mixed-Cation Hybrid Perovskites for Efficient Solar Cells by Mixture Design Methods.

PubMed

Li, Liang; Liu, Na; Xu, Ziqi; Chen, Qi; Wang, Xindong; Zhou, Huanping

2017-09-26

Mixed anion/cation perovskites absorber has been recently implemented to construct highly efficient single junction solar cells and tandem devices. However, considerable efforts are still required to map the composition-property relationship of the mixed perovskites absorber, which is essential to facilitate device design. Here we report the intensive exploration of mixed-cation perovskites in their compositional space with the assistance of a rational mixture design (MD) methods. Different from the previous linear search of the cation ratios, it is found that by employing the MD methods, the ternary composition can be tuned simultaneously following simplex lattice designs or simplex-centroid designs, which enable significantly reduced experiment/sampling size to unveil the composition-property relationship for mixed perovskite materials and to boost the resultant device efficiency. We illustrated the composition-property relationship of the mixed perovskites in multidimension and achieved an optimized power conversion efficiency of 20.99% in the corresponding device. Moreover, the method is demonstrated to be feasible to help adjust the bandgap through rational materials design, which can be further extended to other materials systems, not limited in polycrystalline perovskites films for photovoltaic applications only.

On the Numerical Formulation of Parametric Linear Fractional Transformation (LFT) Uncertainty Models for Multivariate Matrix Polynomial Problems

NASA Technical Reports Server (NTRS)

Belcastro, Christine M.

1998-01-01

Robust control system analysis and design is based on an uncertainty description, called a linear fractional transformation (LFT), which separates the uncertain (or varying) part of the system from the nominal system. These models are also useful in the design of gain-scheduled control systems based on Linear Parameter Varying (LPV) methods. Low-order LFT models are difficult to form for problems involving nonlinear parameter variations. This paper presents a numerical computational method for constructing and LFT model for a given LPV model. The method is developed for multivariate polynomial problems, and uses simple matrix computations to obtain an exact low-order LFT representation of the given LPV system without the use of model reduction. Although the method is developed for multivariate polynomial problems, multivariate rational problems can also be solved using this method by reformulating the rational problem into a polynomial form.

Solving rational matrix equations in the state space with applications to computer-aided control-system design

NASA Technical Reports Server (NTRS)

Packard, A. K.; Sastry, S. S.

1986-01-01

A method of solving a class of linear matrix equations over various rings is proposed, using results from linear geometric control theory. An algorithm, successfully implemented, is presented, along with non-trivial numerical examples. Applications of the method to the algebraic control system design methodology are discussed.

Multi-Step Usage of in Vivo Models During Rational Drug Design and Discovery

PubMed Central

Williams, Charles H.; Hong, Charles C.

2011-01-01

In this article we propose a systematic development method for rational drug design while reviewing paradigms in industry, emerging techniques and technologies in the field. Although the process of drug development today has been accelerated by emergence of computational methodologies, it is a herculean challenge requiring exorbitant resources; and often fails to yield clinically viable results. The current paradigm of target based drug design is often misguided and tends to yield compounds that have poor absorption, distribution, metabolism, and excretion, toxicology (ADMET) properties. Therefore, an in vivo organism based approach allowing for a multidisciplinary inquiry into potent and selective molecules is an excellent place to begin rational drug design. We will review how organisms like the zebrafish and Caenorhabditis elegans can not only be starting points, but can be used at various steps of the drug development process from target identification to pre-clinical trial models. This systems biology based approach paired with the power of computational biology; genetics and developmental biology provide a methodological framework to avoid the pitfalls of traditional target based drug design. PMID:21731440

Development of a Preventive HIV Vaccine Requires Solving Inverse Problems Which Is Unattainable by Rational Vaccine Design

PubMed Central

Van Regenmortel, Marc H. V.

2018-01-01

Hypotheses and theories are essential constituents of the scientific method. Many vaccinologists are unaware that the problems they try to solve are mostly inverse problems that consist in imagining what could bring about a desired outcome. An inverse problem starts with the result and tries to guess what are the multiple causes that could have produced it. Compared to the usual direct scientific problems that start with the causes and derive or calculate the results using deductive reasoning and known mechanisms, solving an inverse problem uses a less reliable inductive approach and requires the development of a theoretical model that may have different solutions or none at all. Unsuccessful attempts to solve inverse problems in HIV vaccinology by reductionist methods, systems biology and structure-based reverse vaccinology are described. The popular strategy known as rational vaccine design is unable to solve the multiple inverse problems faced by HIV vaccine developers. The term “rational” is derived from “rational drug design” which uses the 3D structure of a biological target for designing molecules that will selectively bind to it and inhibit its biological activity. In vaccine design, however, the word “rational” simply means that the investigator is concentrating on parts of the system for which molecular information is available. The economist and Nobel laureate Herbert Simon introduced the concept of “bounded rationality” to explain why the complexity of the world economic system makes it impossible, for instance, to predict an event like the financial crash of 2007–2008. Humans always operate under unavoidable constraints such as insufficient information, a limited capacity to process huge amounts of data and a limited amount of time available to reach a decision. Such limitations always prevent us from achieving the complete understanding and optimization of a complex system that would be needed to achieve a truly rational design process. This is why the complexity of the human immune system prevents us from rationally designing an HIV vaccine by solving inverse problems. PMID:29387066

Final Report: Rational Design of Anode Surface Chemistry in Microbial Fuel Cells for Improved Exoelectrogen Attachment and Electron Transfer

DTIC Science & Technology

2015-12-21

SECURITY CLASSIFICATION OF: The overall goal of this project is to determine how electrode surface chemistry can be rationally designed to decrease...2015 Approved for Public Release; Distribution Unlimited Final Report: Rational Design of Anode Surface Chemistry in Microbial Fuel Cells for...ABSTRACT Final Report: Rational Design of Anode Surface Chemistry in Microbial Fuel Cells for Improved Exoelectrogen Attachment and Electron Transfer

Muck Utilization Planning - Urban Transportation Tunneling : A Handbook of Rational Practices for Planners and Designers

DOT National Transportation Integrated Search

1977-05-01

This handbook alerts transportation system planners and designers to planning methods which can lead to more efficient use of earth and rock materials produced during excavation for transportation tunnels and large excavations. The earth and rock mat...

Artificial intelligence approaches for rational drug design and discovery.

PubMed

Duch, Włodzisław; Swaminathan, Karthikeyan; Meller, Jarosław

2007-01-01

Pattern recognition, machine learning and artificial intelligence approaches play an increasingly important role in rational drug design, screening and identification of candidate molecules and studies on quantitative structure-activity relationships (QSAR). In this review, we present an overview of basic concepts and methodology in the fields of machine learning and artificial intelligence (AI). An emphasis is put on methods that enable an intuitive interpretation of the results and facilitate gaining an insight into the structure of the problem at hand. We also discuss representative applications of AI methods to docking, screening and QSAR studies. The growing trend to integrate computational and experimental efforts in that regard and some future developments are discussed. In addition, we comment on a broader role of machine learning and artificial intelligence approaches in biomedical research.

Beyond directed evolution - semi-rational protein engineering and design

PubMed Central

Lutz, Stefan

2010-01-01

Over the last two decades, directed evolution has transformed the field of protein engineering. The advances in understanding protein structure and function, in no insignificant part a result of directed evolution studies, are increasingly empowering scientists and engineers to device more effective methods for manipulating and tailoring biocatalysts. Abandoning large combinatorial libraries, the focus has shifted to small, functionally-rich libraries and rational design. A critical component to the success of these emerging engineering strategies are computational tools for the evaluation of protein sequence datasets and the analysis of conformational variations of amino acids in proteins. Highlighting the opportunities and limitations of such approaches, this review focuses on recent engineering and design examples that require screening or selection of small libraries. PMID:20869867

Evolutionary and Comparative Genomics to Drive Rational Drug Design, with Particular Focus on Neuropeptide Seven-Transmembrane Receptors.

PubMed

Furlong, Michael; Seong, Jae Young

2017-01-01

Seven transmembrane receptors (7TMRs), also known as G protein-coupled receptors, are popular targets of drug development, particularly 7TMR systems that are activated by peptide ligands. Although many pharmaceutical drugs have been discovered via conventional bulk analysis techniques the increasing availability of structural and evolutionary data are facilitating change to rational, targeted drug design. This article discusses the appeal of neuropeptide-7TMR systems as drug targets and provides an overview of concepts in the evolution of vertebrate genomes and gene families. Subsequently, methods that use evolutionary concepts and comparative analysis techniques to aid in gene discovery, gene function identification, and novel drug design are provided along with case study examples.

Evolutionary and Comparative Genomics to Drive Rational Drug Design, with Particular Focus on Neuropeptide Seven-Transmembrane Receptors

PubMed Central

Furlong, Michael; Seong, Jae Young

2017-01-01

Seven transmembrane receptors (7TMRs), also known as G protein-coupled receptors, are popular targets of drug development, particularly 7TMR systems that are activated by peptide ligands. Although many pharmaceutical drugs have been discovered via conventional bulk analysis techniques the increasing availability of structural and evolutionary data are facilitating change to rational, targeted drug design. This article discusses the appeal of neuropeptide-7TMR systems as drug targets and provides an overview of concepts in the evolution of vertebrate genomes and gene families. Subsequently, methods that use evolutionary concepts and comparative analysis techniques to aid in gene discovery, gene function identification, and novel drug design are provided along with case study examples. PMID:28035082

Applications of different design methodologies in navigation systems and development at JPL

NASA Technical Reports Server (NTRS)

Thurman, S. W.

1990-01-01

The NASA/JPL deep space navigation system consists of a complex array of measurement systems, data processing systems, and support facilities, with components located both on the ground and on-board interplanetary spacecraft. From its beginings nearly 30 years ago, this system has steadily evolved and grown to meet the demands for ever-increasing navigation accuracy placed on it by a succession of unmanned planetary missions. Principal characteristics of this system are its capabilities and great complexity. Three examples in the design and development of interplanetary space navigation systems are examined in order to make a brief assessment of the usefulness of three basic design theories, known as normative, rational, and heuristic. Evaluation of the examples indicates that a heuristic approach, coupled with rational-based mathematical and computational analysis methods, is used most often in problems such as orbit determination strategy development and mission navigation system design, while normative methods have seen only limited use is such applications as the development of large software systems and in the design of certain operational navigation subsystems.

Evaluation of design flood frequency methods for Iowa streams : final report, June 2009.

DOT National Transportation Integrated Search

2009-06-01

The objective of this project was to assess the predictive accuracy of flood frequency estimation for small Iowa streams based : on the Rational Method, the NRCS curve number approach, and the Iowa Runoff Chart. The evaluation was based on : comparis...

Using Caspar Creek flow records to test peak flow estimation methods applicable to crossing design

Treesearch

Peter H. Cafferata; Leslie M. Reid

2017-01-01

Long-term flow records from sub-watersheds in the Caspar Creek Experimental Watersheds were used to test the accuracy of four methods commonly used to estimate peak flows in small forested watersheds: the Rational Method, the updated USGS Magnitude and Frequency Method, flow transference methods, and the NRCS curve number method. Comparison of measured and calculated...

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

PubMed

Tepper, Naama; Shlomi, Tomer

2011-01-21

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

Do Students Use Contextual Protective Behaviors to Reduce Alcohol-Related Sexual Risk? Examination of a Dual-Process Decision-Making Model

PubMed Central

Scaglione, Nichole M.; Hultgren, Brittney A.; Reavy, Racheal; Mallett, Kimberly A.; Turrisi, Rob; Cleveland, Michael J.; Sell, Nichole M.

2015-01-01

Objective Recent studies suggest drinking protective behaviors (DPBs) and contextual protective behaviors (CPBs) can uniquely reduce alcohol-related sexual risk in college students. Few studies have examined CPBs independently, and even fewer have utilized theory to examine modifiable psychosocial predictors of students’ decisions to use CPBs. The current study used a prospective design to examine 1) rational and reactive pathways and psychosocial constructs predictive of CPB use, and 2) how gender might moderate these influences in a sample of college students. Method Students (n = 508) completed web-based baseline (mid-spring semester) and 1- and 6-month follow-up assessments of CPB use; psychosocial constructs (expectancies, normative beliefs, attitudes, and self-concept); and rational and reactive pathways (intentions and willingness). Regression was used to examine rational and reactive influences as proximal predictors of CPB use at the 6-month follow-up. Subsequent path analyses examined the effects of psychosocial constructs, as distal predictors of CPB use, mediated through the rational and reactive pathways. Results Both rational (intentions to use CPB) and reactive (willingness to use CPB) influences were significantly associated with increased CPB use. The examined distal predictors were found to effect CPB use differentially through the rational and reactive pathways. Gender did not significantly moderate any relationships within in the model. Discussion Findings suggest potential entry points for increasing CPB use that include both rational and reactive pathways. Overall, this study demonstrates the mechanisms underlying how to increase the use of CPBs in programs designed to reduce alcohol-related sexual consequences and victimization. PMID:26415062

Method for automation of tool preproduction

NASA Astrophysics Data System (ADS)

Rychkov, D. A.; Yanyushkin, A. S.; Lobanov, D. V.; Arkhipov, P. V.

2018-03-01

The primary objective of tool production is a creation or selection of such tool design which could make it possible to secure high process efficiency, tool availability as well as a quality of received surfaces with minimum means and resources spent on it. It takes much time of application people, being engaged in tool preparation, to make a correct selection of the appropriate tool among the set of variants. Program software has been developed to solve the problem, which helps to create, systematize and carry out a comparative analysis of tool design to identify the rational variant under given production conditions. The literature indicates that systematization and selection of the tool rational design has been carried out in accordance with the developed modeling technology and comparative design analysis. Software application makes it possible to reduce the period of design by 80....85% and obtain a significant annual saving.

Computerized pigment design based on property hypersurfaces

NASA Astrophysics Data System (ADS)

Halova, Jaroslava; Sulcova, Petra; Kupka, Karel

2007-05-01

Competition is tough in the pigment market. Rational pigment design has therefore a competitive advantage, saving time and money. The aim of this work is to provide methods that can assist in designing pigments with defined properties. These methods include partial least squares regression (PLSR), neural network (NN) and generalized regression ANOVA model. Authors show how PLS bi-plot can be used to identify market gaps poorly covered by pigment manufacturers, thus giving an opportunity to develop pigments with potentially profitable properties.

Heat generation in aircraft tires under free rolling conditions

NASA Technical Reports Server (NTRS)

Clark, S. K.; Dodge, R. N.

1980-01-01

Effort is directed toward construction of a rational method for evaluating internal temperatures of aircraft tires. Enhanced predictability of tire temperature buildup is a design tool in both the tire and airframe industries.

Molecular Docking of Enzyme Inhibitors: A Computational Tool for Structure-Based Drug Design

ERIC Educational Resources Information Center

Rudnitskaya, Aleksandra; Torok, Bela; Torok, Marianna

2010-01-01

Molecular docking is a frequently used method in structure-based rational drug design. It is used for evaluating the complex formation of small ligands with large biomolecules, predicting the strength of the bonding forces and finding the best geometrical arrangements. The major goal of this advanced undergraduate biochemistry laboratory exercise…

Designing Genetics Instruction for a Socratic Approach

ERIC Educational Resources Information Center

Idros, Sharifah Norhaidah Syed

2004-01-01

Science is at heart a rational activity. Reasoning, being an important component of critical thinking has been successfully taught using Socratic methods. As an approach, the instructor or designer of instruction models an inquiring and probing mind focusing on providing questions and not answers. The main aim has been to allow learners to…

Non-parametric identification of multivariable systems: A local rational modeling approach with application to a vibration isolation benchmark

NASA Astrophysics Data System (ADS)

Voorhoeve, Robbert; van der Maas, Annemiek; Oomen, Tom

2018-05-01

Frequency response function (FRF) identification is often used as a basis for control systems design and as a starting point for subsequent parametric system identification. The aim of this paper is to develop a multiple-input multiple-output (MIMO) local parametric modeling approach for FRF identification of lightly damped mechanical systems with improved speed and accuracy. The proposed method is based on local rational models, which can efficiently handle the lightly-damped resonant dynamics. A key aspect herein is the freedom in the multivariable rational model parametrizations. Several choices for such multivariable rational model parametrizations are proposed and investigated. For systems with many inputs and outputs the required number of model parameters can rapidly increase, adversely affecting the performance of the local modeling approach. Therefore, low-order model structures are investigated. The structure of these low-order parametrizations leads to an undesired directionality in the identification problem. To address this, an iterative local rational modeling algorithm is proposed. As a special case recently developed SISO algorithms are recovered. The proposed approach is successfully demonstrated on simulations and on an active vibration isolation system benchmark, confirming good performance of the method using significantly less parameters compared with alternative approaches.

Rational Design of Hyperbranched Nanowire Systems for Tunable Superomniphobic Surfaces Enabled by Atomic Layer Deposition

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

Bielinski, Ashley R.; Boban, Mathew; He, Yang

2017-01-24

A method for tunable control of geometry in hyperbranched ZnO nanowire (NW) systems is reported, which enables the rational design and fabrication of superomniphobic surfaces. Branched NWs with tunable density and orientation were grown via a sequential hydrothermal process, in which atomic layer deposition (ALD) was used for NW seeding, disruption of epitaxy, and selective blocking of NW nucleation. This approach allows for the rational design and optimization of three-level hierarchical structures, in which the geometric parameters of each level of hierarchy can be individually controlled. We demonstrate the coupled relationships between geometry and contact angle for a variety ofmore » liquids, which is supported by mathematical models of structural superomniphobicity. The highest performing superomniphobic surface was designed with three levels of hierarchy and achieved the following advancing/receding contact angles, water: 172°/170°, hexadecane: 166°/156°, octane: 162°/145°, and heptane: 160°/130°. Low surface tension liquids were shown to bounce off the surface from a height of 7 cm without breaking through and wetting. This approach demonstrates the power of ALD as an enabling technique for hierarchical materials by design, spanning the macro, micro, and nano length scales.« less

Rational protein design: developing next-generation biological therapeutics and nanobiotechnological tools.

PubMed

Wilson, Corey J

2015-01-01

Proteins are the most functionally diverse macromolecules observed in nature, participating in a broad array of catalytic, biosensing, transport, scaffolding, and regulatory functions. Fittingly, proteins have become one of the most promising nanobiotechnological tools to date, and through the use of recombinant DNA and other laboratory methods we have produced a vast number of biological therapeutics derived from human genes. Our emerging ability to rationally design proteins (e.g., via computational methods) holds the promise of significantly expanding the number and diversity of protein therapies and has opened the gateway to realizing true and uncompromised personalized medicine. In the last decade computational protein design has been transformed from a set of fundamental strategies to stringently test our understanding of the protein structure-function relationship, to practical tools for developing useful biological processes, nano-devices, and novel therapeutics. As protein design strategies improve (i.e., in terms of accuracy and efficiency) clinicians will be able to leverage individual genetic data and biological metrics to develop and deliver personalized protein therapeutics with minimal delay. © 2014 Wiley Periodicals, Inc.

On computing closed forms for summations. [polynomials and rational functions

NASA Technical Reports Server (NTRS)

Moenck, R.

1977-01-01

The problem of finding closed forms for a summation involving polynomials and rational functions is considered. A method closely related to Hermite's method for integration of rational functions derived. The method expresses the sum of a rational function as a rational function part and a transcendental part involving derivatives of the gamma function.

Rational Design of High-Number dsDNA Fragments Based on Thermodynamics for the Construction of Full-Length Genes in a Single Reaction.

PubMed

Birla, Bhagyashree S; Chou, Hui-Hsien

2015-01-01

Gene synthesis is frequently used in modern molecular biology research either to create novel genes or to obtain natural genes when the synthesis approach is more flexible and reliable than cloning. DNA chemical synthesis has limits on both its length and yield, thus full-length genes have to be hierarchically constructed from synthesized DNA fragments. Gibson Assembly and its derivatives are the simplest methods to assemble multiple double-stranded DNA fragments. Currently, up to 12 dsDNA fragments can be assembled at once with Gibson Assembly according to its vendor. In practice, the number of dsDNA fragments that can be assembled in a single reaction are much lower. We have developed a rational design method for gene construction that allows high-number dsDNA fragments to be assembled into full-length genes in a single reaction. Using this new design method and a modified version of the Gibson Assembly protocol, we have assembled 3 different genes from up to 45 dsDNA fragments at once. Our design method uses the thermodynamic analysis software Picky that identifies all unique junctions in a gene where consecutive DNA fragments are specifically made to connect to each other. Our novel method is generally applicable to most gene sequences, and can improve both the efficiency and cost of gene assembly.

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

PubMed

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.

Complete magnesiothermic reduction reaction of vertically aligned mesoporous silica channels to form pure silicon nanoparticles

PubMed Central

Kim, Kyoung Hwan; Lee, Dong Jin; Cho, Kyeong Min; Kim, Seon Joon; Park, Jung-Ki; Jung, Hee-Tae

2015-01-01

Owing to its simplicity and low temperature conditions, magnesiothermic reduction of silica is one of the most powerful methods for producing silicon nanostructures. However, incomplete reduction takes place in this process leaving unconverted silica under the silicon layer. This phenomenon limits the use of this method for the rational design of silicon structures. In this effort, a technique that enables complete magnesiothermic reduction of silica to form silicon has been developed. The procedure involves magnesium promoted reduction of vertically oriented mesoporous silica channels on reduced graphene oxides (rGO) sheets. The mesopores play a significant role in effectively enabling magnesium gas to interact with silica through a large number of reaction sites. Utilizing this approach, highly uniform, ca. 10 nm sized silicon nanoparticles are generated without contamination by unreacted silica. The new method for complete magnesiothermic reduction of mesoporous silica approach provides a foundation for the rational design of silicon structures. PMID:25757800

Rational Design Methodology.

DTIC Science & Technology

1978-09-01

This report describes an effort to specify a software design methodology applicable to the Air Force software environment . Available methodologies...of techniques for proof of correctness, design specification, and performance assessment of static designs. The rational methodology selected is a

Limited Rationality and Its Quantification Through the Interval Number Judgments With Permutations.

PubMed

Liu, Fang; Pedrycz, Witold; Zhang, Wei-Guo

2017-12-01

The relative importance of alternatives expressed in terms of interval numbers in the fuzzy analytic hierarchy process aims to capture the uncertainty experienced by decision makers (DMs) when making a series of comparisons. Under the assumption of full rationality, the judgements of DMs in the typical analytic hierarchy process could be consistent. However, since the uncertainty in articulating the opinions of DMs is unavoidable, the interval number judgements are associated with the limited rationality. In this paper, we investigate the concept of limited rationality by introducing interval multiplicative reciprocal comparison matrices. By analyzing the consistency of interval multiplicative reciprocal comparison matrices, it is observed that the interval number judgements are inconsistent. By considering the permutations of alternatives, the concepts of approximation-consistency and acceptable approximation-consistency of interval multiplicative reciprocal comparison matrices are proposed. The exchange method is designed to generate all the permutations. A novel method of determining the interval weight vector is proposed under the consideration of randomness in comparing alternatives, and a vector of interval weights is determined. A new algorithm of solving decision making problems with interval multiplicative reciprocal preference relations is provided. Two numerical examples are carried out to illustrate the proposed approach and offer a comparison with the methods available in the literature.

Rational design of DNA sequences for nanotechnology, microarrays and molecular computers using Eulerian graphs.

PubMed

Pancoska, Petr; Moravek, Zdenek; Moll, Ute M

2004-01-01

Nucleic acids are molecules of choice for both established and emerging nanoscale technologies. These technologies benefit from large functional densities of 'DNA processing elements' that can be readily manufactured. To achieve the desired functionality, polynucleotide sequences are currently designed by a process that involves tedious and laborious filtering of potential candidates against a series of requirements and parameters. Here, we present a complete novel methodology for the rapid rational design of large sets of DNA sequences. This method allows for the direct implementation of very complex and detailed requirements for the generated sequences, thus avoiding 'brute force' filtering. At the same time, these sequences have narrow distributions of melting temperatures. The molecular part of the design process can be done without computer assistance, using an efficient 'human engineering' approach by drawing a single blueprint graph that represents all generated sequences. Moreover, the method eliminates the necessity for extensive thermodynamic calculations. Melting temperature can be calculated only once (or not at all). In addition, the isostability of the sequences is independent of the selection of a particular set of thermodynamic parameters. Applications are presented for DNA sequence designs for microarrays, universal microarray zip sequences and electron transfer experiments.

Medicinal chemistry inspired fragment-based drug discovery.

PubMed

Lanter, James; Zhang, Xuqing; Sui, Zhihua

2011-01-01

Lead generation can be a very challenging phase of the drug discovery process. The two principal methods for this stage of research are blind screening and rational design. Among the rational or semirational design approaches, fragment-based drug discovery (FBDD) has emerged as a useful tool for the generation of lead structures. It is particularly powerful as a complement to high-throughput screening approaches when the latter failed to yield viable hits for further development. Engagement of medicinal chemists early in the process can accelerate the progression of FBDD efforts by incorporating drug-friendly properties in the earliest stages of the design process. Medium-chain acyl-CoA synthetase 2b and ketohexokinase are chosen as examples to illustrate the importance of close collaboration of medicinal chemists, crystallography, and modeling. Copyright © 2011 Elsevier Inc. All rights reserved.

Revealing Nucleic Acid Mutations Using Förster Resonance Energy Transfer-Based Probes

PubMed Central

Junager, Nina P. L.; Kongsted, Jacob; Astakhova, Kira

2016-01-01

Nucleic acid mutations are of tremendous importance in modern clinical work, biotechnology and in fundamental studies of nucleic acids. Therefore, rapid, cost-effective and reliable detection of mutations is an object of extensive research. Today, Förster resonance energy transfer (FRET) probes are among the most often used tools for the detection of nucleic acids and in particular, for the detection of mutations. However, multiple parameters must be taken into account in order to create efficient FRET probes that are sensitive to nucleic acid mutations. In this review; we focus on the design principles for such probes and available computational methods that allow for their rational design. Applications of advanced, rationally designed FRET probes range from new insights into cellular heterogeneity to gaining new knowledge of nucleic acid structures directly in living cells. PMID:27472344

Spotting and designing promiscuous ligands for drug discovery.

PubMed

Schneider, P; Röthlisberger, M; Reker, D; Schneider, G

2016-01-21

The promiscuous binding behavior of bioactive compounds forms a mechanistic basis for understanding polypharmacological drug action. We present the development and prospective application of a computational tool for identifying potential promiscuous drug-like ligands. In combination with computational target prediction methods, the approach provides a working concept for rationally designing such molecular structures. We could confirm the multi-target binding of a de novo generated compound in a proof-of-concept study relying on the new method.

The Application of Ligand-Mapping Molecular Dynamics Simulations to the Rational Design of Peptidic Modulators of Protein-Protein Interactions.

PubMed

Tan, Yaw Sing; Spring, David R; Abell, Chris; Verma, Chandra S

2015-07-14

A computational ligand-mapping approach to detect protein surface pockets that interact with hydrophobic moieties is presented. In this method, we incorporated benzene molecules into explicit solvent molecular dynamics simulations of various protein targets. The benzene molecules successfully identified the binding locations of hydrophobic hot-spot residues and all-hydrocarbon cross-links from known peptidic ligands. They also unveiled cryptic binding sites that are occluded by side chains and the protein backbone. Our results demonstrate that ligand-mapping molecular dynamics simulations hold immense promise to guide the rational design of peptidic modulators of protein-protein interactions, including that of stapled peptides, which show promise as an exciting new class of cell-penetrating therapeutic molecules.

Hot-spot analysis for drug discovery targeting protein-protein interactions.

PubMed

Rosell, Mireia; Fernández-Recio, Juan

2018-04-01

Protein-protein interactions are important for biological processes and pathological situations, and are attractive targets for drug discovery. However, rational drug design targeting protein-protein interactions is still highly challenging. Hot-spot residues are seen as the best option to target such interactions, but their identification requires detailed structural and energetic characterization, which is only available for a tiny fraction of protein interactions. Areas covered: In this review, the authors cover a variety of computational methods that have been reported for the energetic analysis of protein-protein interfaces in search of hot-spots, and the structural modeling of protein-protein complexes by docking. This can help to rationalize the discovery of small-molecule inhibitors of protein-protein interfaces of therapeutic interest. Computational analysis and docking can help to locate the interface, molecular dynamics can be used to find suitable cavities, and hot-spot predictions can focus the search for inhibitors of protein-protein interactions. Expert opinion: A major difficulty for applying rational drug design methods to protein-protein interactions is that in the majority of cases the complex structure is not available. Fortunately, computational docking can complement experimental data. An interesting aspect to explore in the future is the integration of these strategies for targeting PPIs with large-scale mutational analysis.

Development of quantitative structure-activity relationships and its application in rational drug design.

PubMed

Yang, Guang-Fu; Huang, Xiaoqin

2006-01-01

Over forty years have elapsed since Hansch and Fujita published their pioneering work of quantitative structure-activity relationships (QSAR). Following the introduction of Comparative Molecular Field Analysis (CoMFA) by Cramer in 1998, other three-dimensional QSAR methods have been developed. Currently, combination of classical QSAR and other computational techniques at three-dimensional level is of greatest interest and generally used in the process of modern drug discovery and design. During the last several decades, a number of different mythologies incorporating a range of molecular descriptors and different statistical regression ways have been proposed and successfully applied in developing of new drugs, thus QSAR method has been proven to be indispensable in not only the reliable prediction of specific properties of new compounds, but also the help to elucidate the possible molecular mechanism of the receptor-ligand interactions. Here, we review the recent developments in QSAR and their applications in rational drug design, focusing on the reasonable selection of novel molecular descriptors and the construction of predictive QSAR models by the help of advanced computational techniques.

Solution Synthesis of Atomically Precise Graphene Nanoribbons

NASA Astrophysics Data System (ADS)

Shekhirev, Mikhail; Sinitskii, Alexander

2017-05-01

Bottom-up fabrication of narrow strips of graphene, also known as graphene nanoribbons or GNRs, is an attractive way to open a bandgap in semimetallic graphene. In this chapter, we review recent progress in solution-based synthesis of GNRs with atomically precise structures. We discuss a variety of atomically precise GNRs and highlight theoretical and practical aspects of their structural design and solution synthesis. These GNRs are typically synthesized through a polymerization of rationally designed molecular precursors followed by a planarization through a cyclodehydrogenation reaction. We discuss various synthetic techniques for polymerization and planarization steps, possible approaches for chemical modification of GNRs, and compare the properties of GNRs that could be achieved by different synthetic methods. We also discuss the importance of the rational design of molecular precursors to avoid isomerization during the synthesis and achieve GNRs that have only one possible structure. Significant attention in this chapter is paid to the methods of material characterization of solution-synthesized GNRs. The chapter is concluded with the discussion of the most significant challenges in the field and the future outlook.

In-vitro engineering of novel bioactivity in the natural enzymes

NASA Astrophysics Data System (ADS)

Tiwari, Vishvanath

2016-10-01

Enzymes catalyze various biochemical functions with high efficiency and specificity. In-vitro design of the enzyme leads to novel bioactivity in this natural biomolecule that give answers of some vital questions like crucial residues in binding with substrate, molecular evolution, cofactor specificity etc. Enzyme engineering technology involves directed evolution, rational designing, semi-rational designing and structure-based designing using chemical modifications. Similarly, combined computational and in-vitro evolution approaches together help in artificial designing of novel bioactivity in the natural enzyme. DNA shuffling, error prone PCR and staggered extension process are used to artificially redesign active site of enzyme, which can alter its efficiency and specificity. Modifications of the enzyme can lead to the discovery of new path of molecular evolution, designing of efficient enzymes, locating active sites and crucial residues, shift in substrate and cofactor specificity. The methods and thermodynamics of in-vitro designing of the enzyme are also discussed. Similarly, engineered thermophilic and psychrophilic enzymes attain substrate specificity and activity of mesophilic enzymes that may also be beneficial for industry and therapeutics.

Academic Dishonesty: A Mixed-Method Study of Rational Choice among Students at the College of Basic Education in Kuwait

ERIC Educational Resources Information Center

Alsuwaileh, Bader Ghannam; Russ-Eft, Darlene F.; Alshurai, Saad R.

2016-01-01

The research herein used a sequential mixed methods design to investigate why academic dishonesty is widespread among the students at the College of Basic Education in Kuwait. Qualitative interviews were conducted to generate research hypotheses. Then, using questionnaire survey, the research hypotheses were quantitatively tested. The findings…

Rational design of capillary-driven flows for paper-based microfluidics.

PubMed

Elizalde, Emanuel; Urteaga, Raúl; Berli, Claudio L A

2015-05-21

The design of paper-based assays that integrate passive pumping requires a precise programming of the fluid transport, which has to be encoded in the geometrical shape of the substrate. This requirement becomes critical in multiple-step processes, where fluid handling must be accurate and reproducible for each operation. The present work theoretically investigates the capillary imbibition in paper-like substrates to better understand fluid transport in terms of the macroscopic geometry of the flow domain. A fluid dynamic model was derived for homogeneous porous substrates with arbitrary cross-sectional shapes, which allows one to determine the cross-sectional profile required for a prescribed fluid velocity or mass transport rate. An extension of the model to slit microchannels is also demonstrated. Calculations were validated by experiments with prototypes fabricated in our lab. The proposed method constitutes a valuable tool for the rational design of paper-based assays.

Log D versus HPLC derived hydrophobicity: The development of predictive tools to aid in the rational design of bioactive peptoids

DOE PAGES

Bolt, H. L.; Williams, C. E. J.; Brooks, R. V.; ...

2017-01-13

Hydrophobicity has proven to be an extremely useful parameter in small molecule drug discovery programmes given that it can be used as a predictive tool to enable rational design. For larger molecules, including peptoids, where folding is possible, the situation is more complicated and the average hydrophobicity (as determined by RP-HPLC retention time) may not always provide an effective predictive tool for rational design. Herein, we report the first ever application of partitioning experiments to determine the log D values for a series of peptoids. By comparing log D and average hydrophobicities we highlight the potential advantage of employing themore » former as a predictive tool in the rational design of biologically active peptoids.« less

Log D versus HPLC derived hydrophobicity: The development of predictive tools to aid in the rational design of bioactive peptoids

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

Bolt, H. L.; Williams, C. E. J.; Brooks, R. V.

Hydrophobicity has proven to be an extremely useful parameter in small molecule drug discovery programmes given that it can be used as a predictive tool to enable rational design. For larger molecules, including peptoids, where folding is possible, the situation is more complicated and the average hydrophobicity (as determined by RP-HPLC retention time) may not always provide an effective predictive tool for rational design. Herein, we report the first ever application of partitioning experiments to determine the log D values for a series of peptoids. By comparing log D and average hydrophobicities we highlight the potential advantage of employing themore » former as a predictive tool in the rational design of biologically active peptoids.« less

Treatment of ice cover and other thin elastic layers with the parabolic equation method.

PubMed

Collins, Michael D

2015-03-01

The parabolic equation method is extended to handle problems involving ice cover and other thin elastic layers. Parabolic equation solutions are based on rational approximations that are designed using accuracy constraints to ensure that the propagating modes are handled properly and stability constrains to ensure that the non-propagating modes are annihilated. The non-propagating modes are especially problematic for problems involving thin elastic layers. It is demonstrated that stable results may be obtained for such problems by using rotated rational approximations [Milinazzo, Zala, and Brooke, J. Acoust. Soc. Am. 101, 760-766 (1997)] and generalizations of these approximations. The approach is applied to problems involving ice cover with variable thickness and sediment layers that taper to zero thickness.

Automated design of genetic toggle switches with predetermined bistability.

PubMed

Chen, Shuobing; Zhang, Haoqian; Shi, Handuo; Ji, Weiyue; Feng, Jingchen; Gong, Yan; Yang, Zhenglin; Ouyang, Qi

2012-07-20

Synthetic biology aims to rationally construct biological devices with required functionalities. Methods that automate the design of genetic devices without post-hoc adjustment are therefore highly desired. Here we provide a method to predictably design genetic toggle switches with predetermined bistability. To accomplish this task, a biophysical model that links ribosome binding site (RBS) DNA sequence to toggle switch bistability was first developed by integrating a stochastic model with RBS design method. Then, to parametrize the model, a library of genetic toggle switch mutants was experimentally built, followed by establishing the equivalence between RBS DNA sequences and switch bistability. To test this equivalence, RBS nucleotide sequences for different specified bistabilities were in silico designed and experimentally verified. Results show that the deciphered equivalence is highly predictive for the toggle switch design with predetermined bistability. This method can be generalized to quantitative design of other probabilistic genetic devices in synthetic biology.

Rational Design of Si@SiO2/C Composites Using Sustainable Cellulose as a Carbon Resource for Anodes in Lithium-Ion Batteries.

PubMed

Shen, Dazhi; Huang, Chaofan; Gan, Lihui; Liu, Jian; Gong, Zhengliang; Long, Minnan

2018-03-07

In this work, we propose a novel and facile route for the rational design of Si@SiO 2 /C anode materials by using sustainable and environment-friendly cellulose as a carbon resource. To simultaneously obtain a SiO 2 layer and a carbon scaffold, a specially designed homogeneous cellulose solution and commercial Si nanopowder are used as the starting materials, and the cellulose/Si composite is directly assembled by an in situ regenerating method. Subsequently, Si@SiO 2 /C composite is obtained after carbonization. As expected, Si@SiO 2 is homogeneously encapsulated in the cellulose-derived carbon network. The obtained Si@SiO 2 /C composite shows a high reversible capacity of 1071 mA h g -1 at a current density of 420 mA g -1 and 70% capacity retention after 200 cycles. This novel, sustainable, and effective design is a promising approach to obtain high-performance and cost-effective composite anodes for practical applications.

Designing Artificial Enzymes by Intuition and Computation

PubMed Central

Nanda, Vikas; Koder, Ronald L.

2012-01-01

The rational design of artificial enzymes either by applying physio-chemical intuition of protein structure and function or with the aid of computation methods is a promising area of research with the potential to tremendously impact medicine, industrial chemistry and energy production. Designed proteins also provide a powerful platform for dissecting enzyme mechanisms of natural systems. Artificial enzymes have come a long way, from simple α-helical peptide catalysts to proteins that facilitate multi-step chemical reactions designed by state-of-the-art computational methods. Looking forward, we examine strategies employed by natural enzymes which could be used to improve the speed and selectivity of artificial catalysts. PMID:21124375

The “shape” and “meaning” of the roof arts in Chinese classical architecture

NASA Astrophysics Data System (ADS)

Li, Xianda; liu, Yu

2017-04-01

This paper takes the “roof” in Chinese classical architecture as the research object. The breakthrough point of this paper would be the perspective of design aesthetics. Through the rational and perceptual analysis of the roof art, this paper would reveal that the roof shape has the double artistic features: “beauty of shape” and “beauty of idea”. This paper would have a comprehensive analysis for the following aspects: the rational method of roof construction, the emotional feeling of the roof construction and the implied meaning of beauty in the roof construction.

On the rational design of compressible flow ejectors

NASA Technical Reports Server (NTRS)

Ortwerth, P. J.

1979-01-01

A fluid mechanics review of chemical laser ejectors is presented. The characteristics of ejectors with single and multiple driver nozzles are discussed. Methods to compute an optimized performance map in which secondary Mach number and performance are computed versus mass ratio, to compute the flow distortion at each optimized condition, and to determine the thrust area for the design point to match diffuser impedence are examined.

On implementation of the extended interior penalty function. [optimum structural design

NASA Technical Reports Server (NTRS)

Cassis, J. H.; Schmit, L. A., Jr.

1976-01-01

The extended interior penalty function formulation is implemented. A rational method for determining the transition between the interior and extended parts is set forth. The formulation includes a straightforward method for avoiding design points with some negative components, which are physically meaningless in structural analysis. The technique, when extended to problems involving parametric constraints, can facilitate closed form integration of the penalty terms over the most important parts of the parameter interval. The method lends itself well to the use of approximation concepts, such as design variable linking, constraint deletion and Taylor series expansions of response quantities in terms of design variables. Examples demonstrating the algorithm, in the context of planar orthogonal frames subjected to ground motion, are included.

Target-cancer-cell-specific activatable fluorescence imaging probes: rational design and in vivo applications.

PubMed

Kobayashi, Hisataka; Choyke, Peter L

2011-02-15

Conventional imaging methods, such as angiography, computed tomography (CT), magnetic resonance imaging (MRI), and radionuclide imaging, rely on contrast agents (iodine, gadolinium, and radioisotopes, for example) that are "always on." Although these indicators have proven clinically useful, their sensitivity is lacking because of inadequate target-to-background signal ratio. A unique aspect of optical imaging is that fluorescence probes can be designed to be activatable, that is, only "turned on" under certain conditions. These probes are engineered to emit signal only after binding a target tissue; this design greatly increases sensitivity and specificity in the detection of disease. Current research focuses on two basic types of activatable fluorescence probes. The first developed were conventional enzymatically activatable probes. These fluorescent molecules exist in the quenched state until activated by enzymatic cleavage, which occurs mostly outside of the cells. However, more recently, researchers have begun designing target-cell-specific activatable probes. These fluorophores exist in the quenched state until activated within targeted cells by endolysosomal processing, which results when the probe binds specific receptors on the cell surface and is subsequently internalized. In this Account, we present a review of the rational design and in vivo applications of target-cell-specific activatable probes. In engineering these probes, researchers have asserted control over a variety of factors, including photochemistry, pharmacological profile, and biological properties. Their progress has recently allowed the rational design and synthesis of target-cell-specific activatable fluorescence imaging probes, which can be conjugated to a wide variety of targeting molecules. Several different photochemical mechanisms have been utilized, each of which offers a unique capability for probe design. These include self-quenching, homo- and hetero-fluorescence resonance energy transfer (FRET), H-dimer formation, and photon-induced electron transfer (PeT). In addition, the repertoire is further expanded by the option for reversibility or irreversibility of the signal emitted through these mechanisms. Given the wide range of photochemical mechanisms and properties, target-cell-specific activatable probes have considerable flexibility and can be adapted to specific diagnostic needs. A multitude of cell surface molecules, such as overexpressed growth factor receptors, are directly related to carcinogenesis and thus provide numerous targets highly specific for cancer. This discussion of the chemical, pharmacological, and biological basis of target-cell-specific activatable imaging probes, and methods for successfully designing them, underscores the systematic, rational basis for further developing in vivo cancer imaging.

Target-cancer cell specific activatable fluorescence imaging Probes: Rational Design and in vivo Applications

PubMed Central

Kobayashi, Hisataka; Choyke, Peter L.

2010-01-01

CONSPECTUS Conventional imaging methods, such as angiography, computed tomography, magnetic resonance imaging and radionuclide imaging, rely on contrast agents (iodine, gadolinium, radioisotopes) that are “always on”. While these agents have proven clinically useful, they are not sufficiently sensitive because of the inadequate target to background ratio. A unique aspect of optical imaging is that fluorescence probes can be designed to be activatable, i.e. only “turned on” under certain conditions. These probes can be designed to emit signal only after binding a target tissue, greatly increasing sensitivity and specificity in the detection of disease. There are two basic types of activatable fluorescence probes; 1) conventional enzymatically activatable probes, which exist in the quenched state until activated by enzymatic cleavage mostly outside of the cells, and 2) newly designed target-cell specific activatable probes, which are quenched until activated in targeted cells by endolysosomal processing that results when the probe binds specific cell-surface receptors and is subsequently internalized. Herein, we present a review of the rational design and in vivo applications of target-cell specific activatable probes. Designing these probes based on their photo-chemical (e.g. activation strategy), pharmacological (e.g. biodistribution), and biological (e.g. target specificity) properties has recently allowed the rational design and synthesis of target-cell specific activatable fluorescence imaging probes, which can be conjugated to a wide variety of targeting molecules. Several different photo-chemical mechanisms have been utilized, each of which offers a unique capability for probe design. These include: self-quenching, homo- and hetero-fluorescence resonance energy transfer (FRET), H-dimer formation and photon-induced electron transfer (PeT). In addition, the repertoire is further expanded by the option for reversibility or irreversibility of the signal emitted using the aforementioned mechanisms. Given the wide range of photochemical mechanisms and properties, target-cell specific activatable probes possess considerable flexibility and can be adapted to specific diagnostic needs. Herein, we summarize the chemical, pharmacological, and biological basis of target-cell specific activatable imaging probes and discuss methods to successfully design such target-cell specific activatable probes for in vivo cancer imaging. PMID:21062101

14 CFR 29.427 - Unsymmetrical loads.

Code of Federal Regulations, 2010 CFR

2010-01-01

... conditions. (b) To meet the design criteria of paragraph (a) of this section, in the absence of more rational... selected so that the maximum design loads are obtained on each surface. In the absence of more rational...

14 CFR 27.427 - Unsymmetrical loads.

Code of Federal Regulations, 2010 CFR

2010-01-01

... conditions. (b) To meet the design criteria of paragraph (a) of this section, in the absence of more rational... selected so the maximum design loads are obtained on each surface. In the absence of more rational data...

Rational drug therapy education in clinical phase carried out by task-based learning

PubMed Central

Bilge, S. Sırrı; Akyüz, Bahar; Ağrı, Arzu Erdal; Özlem, Mıdık

2017-01-01

Objectives: Irrational drug use results in drug interactions, treatment noncompliance, and drug resistance. Rational pharmacotherapy education is being implemented in many faculties of medicine. Our aim is to introduce rational pharmacotherapy education by clinicians and to evaluate task-based rational drug therapy education in the clinical context. Methods: The Kirkpatrick's evaluation model was used for the evaluation of the program. The participants evaluated the program in terms of constituents of the program, utilization, and contribution to learning. Voluntary participants responded to the evaluation forms after the educational program. Data are evaluated using both quantitative and qualitative tools. SPSS (version 21) used for quantitative data for determining mean and standard deviation values. Descriptive qualitative analysis approach is used for the analysis of open-ended questions. Results: It was revealed that the program and its components have been favorable. A total 95.9% of the students consider the education to be beneficial. Simulated patients practice and personal drug choice/problem-based learning sessions were appreciated by the students in particular. 93.9% of the students stated that all students of medicine should undergo this educational program. Among the five presentations contained in the program, “The Principles of Prescribing” received the highest points (9 ± 1.00) from participating students in general evaluation of the educational program. Conclusion: This study was carried out to improve task-based rational drug therapy education. According to feedback from the students concerning content, method, resource, assessment, and program design; some important changes, especially in number of facilitators and indications, are made in rational pharmacotherapy education in clinical task-based learning program. PMID:28458432

Model-based rational feedback controller design for closed-loop deep brain stimulation of Parkinson's disease

NASA Astrophysics Data System (ADS)

Gorzelic, P.; Schiff, S. J.; Sinha, A.

2013-04-01

Objective. To explore the use of classical feedback control methods to achieve an improved deep brain stimulation (DBS) algorithm for application to Parkinson's disease (PD). Approach. A computational model of PD dynamics was employed to develop model-based rational feedback controller design. The restoration of thalamocortical relay capabilities to patients suffering from PD is formulated as a feedback control problem with the DBS waveform serving as the control input. Two high-level control strategies are tested: one that is driven by an online estimate of thalamic reliability, and another that acts to eliminate substantial decreases in the inhibition from the globus pallidus interna (GPi) to the thalamus. Control laws inspired by traditional proportional-integral-derivative (PID) methodology are prescribed for each strategy and simulated on this computational model of the basal ganglia network. Main Results. For control based upon thalamic reliability, a strategy of frequency proportional control with proportional bias delivered the optimal control achieved for a given energy expenditure. In comparison, control based upon synaptic inhibitory output from the GPi performed very well in comparison with those of reliability-based control, with considerable further reduction in energy expenditure relative to that of open-loop DBS. The best controller performance was amplitude proportional with derivative control and integral bias, which is full PID control. We demonstrated how optimizing the three components of PID control is feasible in this setting, although the complexity of these optimization functions argues for adaptive methods in implementation. Significance. Our findings point to the potential value of model-based rational design of feedback controllers for Parkinson's disease.

Model-based rational feedback controller design for closed-loop deep brain stimulation of Parkinson's disease.

PubMed

Gorzelic, P; Schiff, S J; Sinha, A

2013-04-01

To explore the use of classical feedback control methods to achieve an improved deep brain stimulation (DBS) algorithm for application to Parkinson's disease (PD). A computational model of PD dynamics was employed to develop model-based rational feedback controller design. The restoration of thalamocortical relay capabilities to patients suffering from PD is formulated as a feedback control problem with the DBS waveform serving as the control input. Two high-level control strategies are tested: one that is driven by an online estimate of thalamic reliability, and another that acts to eliminate substantial decreases in the inhibition from the globus pallidus interna (GPi) to the thalamus. Control laws inspired by traditional proportional-integral-derivative (PID) methodology are prescribed for each strategy and simulated on this computational model of the basal ganglia network. For control based upon thalamic reliability, a strategy of frequency proportional control with proportional bias delivered the optimal control achieved for a given energy expenditure. In comparison, control based upon synaptic inhibitory output from the GPi performed very well in comparison with those of reliability-based control, with considerable further reduction in energy expenditure relative to that of open-loop DBS. The best controller performance was amplitude proportional with derivative control and integral bias, which is full PID control. We demonstrated how optimizing the three components of PID control is feasible in this setting, although the complexity of these optimization functions argues for adaptive methods in implementation. Our findings point to the potential value of model-based rational design of feedback controllers for Parkinson's disease.

Rational Design of Cancer-Targeted Benzoselenadiazole by RGD Peptide Functionalization for Cancer Theranostics.

PubMed

Yang, Liye; Li, Wenying; Huang, Yanyu; Zhou, Yangliang; Chen, Tianfeng

2015-09-01

A cancer-targeted conjugate of the selenadiazole derivative BSeC (benzo[1,2,5] selenadiazole-5-carboxylic acid) with RGD peptide as targeting molecule and PEI (polyethylenimine) as a linker is rationally designed and synthesized in the present study. The results show that RGD-PEI-BSeC forms nanoparticles in aqueous solution with a core-shell nanostructure and high stability under physiological conditions. This rational design effectively enhances the selective cellular uptake and cellular retention of BSeC in human glioma cells, and increases its selectivity between cancer and normal cells. The nanoparticles enter the cells through receptor-mediated endocytosis via clathrin-mediated and nystatin-dependent lipid raft-mediated pathways. Internalized nanoparticles trigger glioma cell apoptosis by activation of ROS-mediated p53 phosphorylation. Therefore, this study provides a strategy for the rational design of selenium-containing cancer-targeted theranostics. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Negotiating a Systems Development Method

NASA Astrophysics Data System (ADS)

Karlsson, Fredrik; Hedström, Karin

Systems development methods (or methods) are often applied in tailored version to fit the actual situation. Method tailoring is in most the existing literature viewed as either (a) a highly rational process with the method engineer as the driver where the project members are passive information providers or (b) an unstructured process where the systems developer makes individual choices, a selection process without any driver. The purpose of this chapter is to illustrate that important design decisions during method tailoring are made by project members through negotiation. The study has been carried out using the perspective of actor-network theory. Our narratives depict method tailoring as more complex than (a) and (b) show the driver role rotates between the project members, and design decisions are based on influences from several project members. However, these design decisions are not consensus decisions.

New directions in the rational design of electrical and magnetic seizure therapies: individualized Low Amplitude Seizure Therapy (iLAST) and Magnetic Seizure Therapy (MST).

PubMed

Radman, Thomas; Lisanby, Sarah H

2017-04-01

Electroconvulsive therapy remains a key treatment option for severe cases of depression, but undesirable side-effects continue to limit its use. Innovations in the design of novel seizure therapies seek to improve its risk benefit ratio through enhanced control of the focality of stimulation. The design of seizure therapies with increased spatial precision is motivated by avoiding stimulation of deep brain structures implicated in memory retention, including the hippocampus. The development of two innovations in seizure therapy-individualized low-amplitude seizure therapy (iLAST) and magnetic seizure therapy (MST), are detailed. iLAST is a method of seizure titration involving reducing current spread in the brain by titrating current amplitude from the traditional fixed amplitudes. MST, which can be used in conjunction with iLAST dosing methods, involves the use of magnetic stimulation to reduce shunting and spreading of current by the scalp occurring during electrical stimulation. Evidence is presented on the rationale for increasing the focality of ECT in hopes of preserving its effectiveness, while reducing cognitive side-effects. Finally, the value of electric field and neural modelling is illustrated to explain observed clinical effects of modifications to ECT technique, and their utility in the rational design of the next generation of seizure therapies.

Fibrin-based biomaterials: Modulation of macroscopic properties through rational design at the molecular level

PubMed Central

Brown, Ashley C.; Barker, Thomas H.

2013-01-01

Fibrinogen is one of the primary components of the coagulation cascade and rapidly forms an insoluble matrix following tissue injury. In addition to its important role in hemostasis, fibrin acts as a scaffold for tissue repair and provides important cues for directing cell phenotype following injury. Because of these properties and the ease of polymerization of the material, fibrin has been widely utilized as a biomaterial for over a century. Modifying the macroscopic properties of fibrin, such as elasticity and porosity, has been somewhat elusive until recently, yet with a molecular-level rational design approach can now be somewhat easily modified through alterations of molecular interactions key to the protein’s polymerization process. This review outlines the biochemistry of fibrin and discusses methods for modification of molecular interactions and their application to fibrin based biomaterials. PMID:24056097

Advanced optical manufacturing digital integrated system

NASA Astrophysics Data System (ADS)

Tao, Yizheng; Li, Xinglan; Li, Wei; Tang, Dingyong

2012-10-01

It is necessarily to adapt development of advanced optical manufacturing technology with modern science technology development. To solved these problems which low of ration, ratio of finished product, repetition, consistent in big size and high precision in advanced optical component manufacturing. Applied business driven and method of Rational Unified Process, this paper has researched advanced optical manufacturing process flow, requirement of Advanced Optical Manufacturing integrated System, and put forward architecture and key technology of it. Designed Optical component core and Manufacturing process driven of Advanced Optical Manufacturing Digital Integrated System. the result displayed effective well, realized dynamic planning Manufacturing process, information integration improved ratio of production manufactory.

Identification of novel targets for HIV-1: Molecular dynamics simulation and binding energy calculations

NASA Astrophysics Data System (ADS)

Pandey, Vishnudatt; Tiwari, Gargi; Mall, Vijaya Shri; Tiwari, Rakesh Kumar; Ojha, R. P.

2018-05-01

HIV-1 envelope glycoprotein-mediated fusion is managed by the concerted coalescence of the HIV-1 gp41 N- and C- helical regions, which is a product in the formation of 6-helix bundles. These two regions are considered prime targets for peptides and antibodies that inhibit HIV-1 entry. There are so many rational method aimed to attach a rationally designed artificial tail to the C-terminus of HIV-1 fusion inhibitors to increase their antiviral potency. Here M. D. simulation was performed to go insight for study of C-terminal tail of Ile-Asp-Leu (IDL).

Molecular and macro-scale analysis of enzyme-crosslinked silk hydrogels for rational biomaterial design.

PubMed

McGill, Meghan; Coburn, Jeannine M; Partlow, Benjamin P; Mu, Xuan; Kaplan, David L

2017-11-01

Silk fibroin-based hydrogels have exciting applications in tissue engineering and therapeutic molecule delivery; however, their utility is dependent on their diffusive properties. The present study describes a molecular and macro-scale investigation of enzymatically-crosslinked silk fibroin hydrogels, and demonstrates that these systems have tunable crosslink density and diffusivity. We developed a liquid chromatography tandem mass spectroscopy (LC-MS/MS) method to assess the quantity and order of covalent tyrosine crosslinks in the hydrogels. This analysis revealed between 28 and 56% conversion of tyrosine to dityrosine, which was dependent on the silk concentration and reactant concentration. The crosslink density was then correlated with storage modulus, revealing that both crosslinking and protein concentration influenced the mechanical properties of the hydrogels. The diffusive properties of the bulk material were studied by fluorescence recovery after photobleaching (FRAP), which revealed a non-linear relationship between silk concentration and diffusivity. As a result of this work, a model for synthesizing hydrogels with known crosslink densities and diffusive properties has been established, enabling the rational design of silk hydrogels for biomedical applications. Hydrogels from naturally-derived silk polymers offer versitile opportunities in the biomedical field, however, their design has largely been an empirical process. We present a fundamental study of the crosslink density, storage modulus, and diffusion behavior of enzymatically-crosslinked silk hydrogels to better inform scaffold design. These studies revealed unexpected non-linear trends in the crosslink density and diffusivity of silk hydrogels with respect to protein concentration and crosslink reagent concentration. This work demonstrates the tunable diffusivity and crosslinking in silk fibroin hydrogels, and enables the rational design of biomaterials. Further, the characterization methods presented have applications for other materials with dityrosine crosslinks, which are found in nature as post-translational modificaitons, as well as in engineered matrices such as tyramine-substituted hyaluronic acid and recombinant resilin. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Rational modification of protein stability by targeting surface sites leads to complicated results

PubMed Central

Xiao, Shifeng; Patsalo, Vadim; Shan, Bing; Bi, Yuan; Green, David F.; Raleigh, Daniel P.

2013-01-01

The rational modification of protein stability is an important goal of protein design. Protein surface electrostatic interactions are not evolutionarily optimized for stability and are an attractive target for the rational redesign of proteins. We show that surface charge mutants can exert stabilizing effects in distinct and unanticipated ways, including ones that are not predicted by existing methods, even when only solvent-exposed sites are targeted. Individual mutation of three solvent-exposed lysines in the villin headpiece subdomain significantly stabilizes the protein, but the mechanism of stabilization is very different in each case. One mutation destabilizes native-state electrostatic interactions but has a larger destabilizing effect on the denatured state, a second removes the desolvation penalty paid by the charged residue, whereas the third introduces unanticipated native-state interactions but does not alter electrostatics. Our results show that even seemingly intuitive mutations can exert their effects through unforeseen and complex interactions. PMID:23798426

Grid Based Technologies for in silico Screening and Drug Design.

PubMed

Potemkin, Vladimir; Grishina, Maria

2018-03-08

Various techniques for rational drug design are presented in the paper. The methods are based on a substitution of antipharmacophore atoms of the molecules of training dataset by new atoms and/or group of atoms increasing the atomic bioactivity increments obtained at a SAR study. Furthermore, a design methodology based on the genetic algorithm DesPot for discrete optimization and generation of new drug candidate structures is described. Additionally, wide spectra of SAR approaches (3D/4D QSAR interior and exterior-based methods - BiS, CiS, ConGO, CoMIn, high-quality docking method - ReDock) using MERA force field and/or AlteQ quantum chemical method for correct prognosis of bioactivity and bioactive probability is described. The design methods are implemented now at www.chemosophia.com web-site for online computational services. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Machine learning in the rational design of antimicrobial peptides.

PubMed

Rondón-Villarreal, Paola; Sierra, Daniel A; Torres, Rodrigo

2014-01-01

One of the most important public health issues is the microbial and bacterial resistance to conventional antibiotics by pathogen microorganisms. In recent years, many researches have been focused on the development of new antibiotics. Among these, antimicrobial peptides (AMPs) have raised as a promising alternative to combat antibioticresistant microorganisms. For this reason, many theoretical efforts have been done in the development of new computational tools for the rational design of both better and effective AMPs. In this review, we present an overview of the rational design of AMPs using machine learning techniques and new research fields.

Rational design of crystal contact-free space in protein crystals for analyzing spatial distribution of motions within protein molecules.

PubMed

Matsuoka, Rei; Shimada, Atsushi; Komuro, Yasuaki; Sugita, Yuji; Kohda, Daisuke

2016-03-01

Contacts with neighboring molecules in protein crystals inevitably restrict the internal motions of intrinsically flexible proteins. The resultant clear electron densities permit model building, as crystallographic snapshot structures. Although these still images are informative, they could provide biased pictures of the protein motions. If the mobile parts are located at a site lacking direct contacts in rationally designed crystals, then the amplitude of the movements can be experimentally analyzed. We propose a fusion protein method, to create crystal contact-free space (CCFS) in protein crystals and to place the mobile parts in the CCFS. Conventional model building fails when large amplitude motions exist. In this study, the mobile parts appear as smeared electron densities in the CCFS, by suitable processing of the X-ray diffraction data. We applied the CCFS method to a highly mobile presequence peptide bound to the mitochondrial import receptor, Tom20, and a catalytically relevant flexible segment in the oligosaccharyltransferase, AglB. These two examples demonstrated the general applicability of the CCFS method to the analysis of the spatial distribution of motions within protein molecules. © 2016 The Protein Society.

Designing Image Analysis Pipelines in Light Microscopy: A Rational Approach.

PubMed

Arganda-Carreras, Ignacio; Andrey, Philippe

2017-01-01

With the progress of microscopy techniques and the rapidly growing amounts of acquired imaging data, there is an increased need for automated image processing and analysis solutions in biological studies. Each new application requires the design of a specific image analysis pipeline, by assembling a series of image processing operations. Many commercial or free bioimage analysis software are now available and several textbooks and reviews have presented the mathematical and computational fundamentals of image processing and analysis. Tens, if not hundreds, of algorithms and methods have been developed and integrated into image analysis software, resulting in a combinatorial explosion of possible image processing sequences. This paper presents a general guideline methodology to rationally address the design of image processing and analysis pipelines. The originality of the proposed approach is to follow an iterative, backwards procedure from the target objectives of analysis. The proposed goal-oriented strategy should help biologists to better apprehend image analysis in the context of their research and should allow them to efficiently interact with image processing specialists.

Applicability of linearized-theory attached-flow methods to design and analysis of flap systems at low speeds for thin swept wings with sharp leading edges

NASA Technical Reports Server (NTRS)

Carlson, Harry W.; Darden, Christine M.

1987-01-01

Low-speed experimental force and data on a series of thin swept wings with sharp leading edges and leading and trailing-edge flaps are compared with predictions made using a linearized-theory method which includes estimates of vortex forces. These comparisons were made to assess the effectiveness of linearized-theory methods for use in the design and analysis of flap systems in subsonic flow. Results demonstrate that linearized-theory, attached-flow methods (with approximate representation of vortex forces) can form the basis of a rational system for flap design and analysis. Even attached-flow methods that do not take vortex forces into account can be used for the selection of optimized flap-system geometry, but design-point performance levels tend to be underestimated unless vortex forces are included. Illustrative examples of the use of these methods in the design of efficient low-speed flap systems are included.

Systems metabolic engineering: the creation of microbial cell factories by rational metabolic design and evolution.

PubMed

Furusawa, Chikara; Horinouchi, Takaaki; Hirasawa, Takashi; Shimizu, Hiroshi

2013-01-01

It is widely acknowledged that in order to establish sustainable societies, production processes should shift from petrochemical-based processes to bioprocesses. Because bioconversion technologies, in which biomass resources are converted to valuable materials, are preferable to processes dependent on fossil resources, the former should be further developed. The following two approaches can be adopted to improve cellular properties and obtain high productivity and production yield of target products: (1) optimization of cellular metabolic pathways involved in various bioprocesses and (2) creation of stress-tolerant cells that can be active even under severe stress conditions in the bioprocesses. Recent progress in omics analyses has facilitated the analysis of microorganisms based on bioinformatics data for molecular breeding and bioprocess development. Systems metabolic engineering is a new area of study, and it has been defined as a methodology in which metabolic engineering and systems biology are integrated to upgrade the designability of industrially useful microorganisms. This chapter discusses multi-omics analyses and rational design methods for molecular breeding. The first is an example of the rational design of metabolic networks for target production by flux balance analysis using genome-scale metabolic models. Recent progress in the development of genome-scale metabolic models and the application of these models to the design of desirable metabolic networks is also described in this example. The second is an example of evolution engineering with omics analyses for the creation of stress-tolerant microorganisms. Long-term culture experiments to obtain the desired phenotypes and omics analyses to identify the phenotypic changes are described here.

Rational Emotive Education

ERIC Educational Resources Information Center

Knaus, William

1977-01-01

Rational Emotive Education--an outgrowth of theories developed by Albert Ellis--is a teaching design of mental health concepts and problem-solving activities designed to help students to approach and cope with their problems through experiential learning, via a structured, thematic sequence of emotive education lessons. (MJB)

MDO can help resolve the designer's dilemma. [multidisciplinary design optimization

NASA Technical Reports Server (NTRS)

Sobieszczanski-Sobieski, Jaroslaw; Tulinius, Jan R.

1991-01-01

Multidisciplinary design optimization (MDO) is presented as a rapidly growing body of methods, algorithms, and techniques that will provide a quantum jump in the effectiveness and efficiency of the quantitative side of design, and will turn that side into an environment in which the qualitative side can thrive. MDO borrows from CAD/CAM for graphic visualization of geometrical and numerical data, data base technology, and in computer software and hardware. Expected benefits from this methodology are a rational, mathematically consistent approach to hypersonic aircraft designs, designs pushed closer to the optimum, and a design process either shortened or leaving time available for different concepts to be explored.

Return period adjustment for runoff coefficients based on analysis in undeveloped Texas watersheds

USGS Publications Warehouse

Dhakal, Nirajan; Fang, Xing; Asquith, William H.; Cleveland, Theodore G.; Thompson, David B.

2013-01-01

The rational method for peak discharge (Qp) estimation was introduced in the 1880s. The runoff coefficient (C) is a key parameter for the rational method that has an implicit meaning of rate proportionality, and the C has been declared a function of the annual return period by various researchers. Rate-based runoff coefficients as a function of the return period, C(T), were determined for 36 undeveloped watersheds in Texas using peak discharge frequency from previously published regional regression equations and rainfall intensity frequency for return periods T of 2, 5, 10, 25, 50, and 100 years. The C(T) values and return period adjustments C(T)/C(T=10  year) determined in this study are most applicable to undeveloped watersheds. The return period adjustments determined for the Texas watersheds in this study and those extracted from prior studies of non-Texas data exceed values from well-known literature such as design manuals and textbooks. Most importantly, the return period adjustments exceed values currently recognized in Texas Department of Transportation design guidance when T>10  years.

Linking patient satisfaction with nursing care: the case of care rationing - a correlational study

PubMed Central

2014-01-01

Background Implicit rationing of nursing care is the withholding of or failure to carry out all necessary nursing measures due to lack of resources. There is evidence supporting a link between rationing of nursing care, nurses’ perceptions of their professional environment, negative patient outcomes, and placing patient safety at risk. The aims of the study were: a) To explore whether patient satisfaction is linked to nurse-reported rationing of nursing care and to nurses’ perceptions of their practice environment while adjusting for patient and nurse characteristics. b) To identify the threshold score of rationing by comparing the level of patient satisfaction factors across rationing levels. Methods A descriptive, correlational design was employed. Participants in this study included 352 patients and 318 nurses from ten medical and surgical units of five general hospitals. Three measurement instruments were used: the BERNCA scale for rationing of care, the RPPE scale to explore nurses’ perceptions of their work environment and the Patient Satisfaction scale to assess the level of patient satisfaction with nursing care. The statistical analysis included the use of Kendall’s correlation coefficient to explore a possible relationship between the variables and multiple regression analysis to assess the effects of implicit rationing of nursing care together with organizational characteristics on patient satisfaction. Results The mean score of implicit rationing of nursing care was 0.83 (SD = 0.52, range = 0–3), the overall mean of RPPE was 2.76 (SD = 0.32, range = 1.28 – 3.69) and the two scales were significantly correlated (τ = −0.234, p < 0.001). The regression analysis showed that care rationing and work environment were related to patient satisfaction, even after controlling for nurse and patient characteristics. The results from the adjusted regression models showed that even at the lowest level of rationing (i.e. 0.5) patients indicated low satisfaction. Conclusions The results support the relationships between organizational and environmental variables, care rationing and patient satisfaction. The identification of thresholds at which rationing starts to influence patient outcomes in a negative way may allow nurse managers to introduce interventions so as to keep rationing at a level at which patient safety is not jeopardized. PMID:25285040

Abnormality, rationality, and sanity.

PubMed

Hertwig, Ralph; Volz, Kirsten G

2013-11-01

A growing body of studies suggests that neurological and mental abnormalities foster conformity to norms of rationality that are widely endorsed in economics and psychology, whereas normality stands in the way of rationality thus defined. Here, we outline the main findings of these studies, discuss their implications for experimental design, and consider how 'sane' some benchmarks of rationality really are. Copyright © 2013 Elsevier Ltd. All rights reserved.

Aeroservoelastic modeling and applications using minimum-state approximations of the unsteady aerodynamics

NASA Technical Reports Server (NTRS)

Tiffany, Sherwood H.; Karpel, Mordechay

1989-01-01

Various control analysis, design, and simulation techniques for aeroelastic applications require the equations of motion to be cast in a linear time-invariant state-space form. Unsteady aerodynamics forces have to be approximated as rational functions of the Laplace variable in order to put them in this framework. For the minimum-state method, the number of denominator roots in the rational approximation. Results are shown of applying various approximation enhancements (including optimization, frequency dependent weighting of the tabular data, and constraint selection) with the minimum-state formulation to the active flexible wing wind-tunnel model. The results demonstrate that good models can be developed which have an order of magnitude fewer augmenting aerodynamic equations more than traditional approaches. This reduction facilitates the design of lower order control systems, analysis of control system performance, and near real-time simulation of aeroservoelastic phenomena.

Evolving serodiagnostics by rationally designed peptide arrays: the Burkholderia paradigm in Cystic Fibrosis

NASA Astrophysics Data System (ADS)

Peri, Claudio; Gori, Alessandro; Gagni, Paola; Sola, Laura; Girelli, Daniela; Sottotetti, Samantha; Cariani, Lisa; Chiari, Marcella; Cretich, Marina; Colombo, Giorgio

2016-09-01

Efficient diagnosis of emerging and novel bacterial infections is fundamental to guide decisions on therapeutic treatments. Here, we engineered a novel rational strategy to design peptide microarray platforms, which combines structural and genomic analyses to predict the binding interfaces between diverse protein antigens and antibodies against Burkholderia cepacia complex infections present in the sera of Cystic Fibrosis (CF) patients. The predicted binding interfaces on the antigens are synthesized in the form of isolated peptides and chemically optimized for controlled orientation on the surface. Our platform displays multiple Burkholderia-related epitopes and is shown to diagnose infected individuals even in presence of superinfections caused by other prevalent CF pathogens, with limited cost and time requirements. Moreover, our data point out that the specific patterns determined by combined probe responses might provide a characterization of Burkholderia infections even at the subtype level (genomovars). The method is general and immediately applicable to other bacteria.

Coupled Triboelectric Nanogenerator Networks for Efficient Water Wave Energy Harvesting.

PubMed

Xu, Liang; Jiang, Tao; Lin, Pei; Shao, Jia Jia; He, Chuan; Zhong, Wei; Chen, Xiang Yu; Wang, Zhong Lin

2018-02-27

Water wave energy is a promising clean energy source, which is abundant but hard to scavenge economically. Triboelectric nanogenerator (TENG) networks provide an effective approach toward massive harvesting of water wave energy in oceans. In this work, a coupling design in TENG networks for such purposes is reported. The charge output of the rationally linked units is over 10 times of that without linkage. TENG networks of three different connecting methods are fabricated and show better performance for the ones with flexible connections. The network is based on an optimized ball-shell structured TENG unit with high responsivity to small agitations. The dynamic behavior of single and multiple TENG units is also investigated comprehensively to fully understand their performance in water. The study shows that a rational design on the linkage among the units could be an effective strategy for TENG clusters to operate collaboratively for reaching a higher performance.

Live Attenuated Influenza Vaccines by Computer-Aided Rational Design

PubMed Central

Mueller, Steffen; Coleman, J. Robert; Papamichail, Dimitris; Ward, Charles B.; Nimnual, Anjaruwee; Futcher, Bruce; Skiena, Steven; Wimmer, Eckard

2010-01-01

Influenza claims 250,000 - 500,000 lives annually worldwide. Despite existing vaccines and enormous efforts in biomedical research, these staggering numbers have not changed significantly over the last two decades1, motivating the search for new, more effective, vaccines that can be rapidly designed and easily produced. Using influenza virus strain A/PR/8/34, we describe a systematic, rational approach, termed Synthetic Attenuated Virus Engineering (SAVE), to develop new, efficacious live attenuated influenza virus vaccine candidates through genome-scale changes in codon pair bias. Attenuation is based on many hundreds of nucleotide changes across the viral genome, offering high genetic stability and a wide margin of safety. The method can be applied rapidly to any emerging influenza virus in its entirety, an advantage that is significant for dealing with seasonal epidemics and pandemic threats, such as H5N1- or 2009-H1N1 influenza. PMID:20543832

US neurologists: attitudes on rationing.

PubMed

Holloway, R G; Ringel, S P; Bernat, J L; Keran, C M; Lawyer, B L

2000-11-28

To assess neurologists' attitudes on rationing health care and to determine whether neurologists would set healthcare priorities in ways that are consistent with cost-effectiveness research. Cost-effectiveness research can suggest ways to maximize health benefits within fixed budgets but is currently being underused in resource allocation decisions. The authors surveyed a random sample of neurologists practicing in the United States (response rate, 44.4%) with three hypothetical scenarios. Two scenarios were designed to address general attitudes on allocating finite resources with emphasis on formulary decisions for costly drugs. The third scenario was designed to assess whether neurologists would optimize the allocation of a fixed budget as recommended by cost-effectiveness analysis. Three-quarters of respondents thought that neurologists make daily decisions that effectively ration healthcare resources, and 60% felt a professional responsibility to consider the financial impact of individualized treatment decisions on other patients. Only 25% of respondents thought that there should be no restrictions placed on any of the five newer antiepileptic agents. In a 1995 survey, 75% of similarly sampled neurologists agreed that no restrictions should be placed on the availability of FDA-approved medications. Nearly half (46%) of respondents favored a less effective test and would be willing to let patients die to ensure the offering of a more equitable alternative. Most neurologists recognize the need to ration health care, and although they think cost-effectiveness research is one method to achieve efficient distribution of resources, many think that considerable attention should also be given to equity.

The political economy of rationing health care in England and the US: the 'accidental logics' of political settlements.

PubMed

Bevan, Gwyn; Brown, Lawrence D

2014-07-01

This article considers how the 'accidental logics' of political settlements for the English National Health Service (NHS) and the Medicare and Medicaid programmes in the United States have resulted in different institutional arrangements and different implicit social contracts for rationing, which we define to be the denial of health care that is beneficial but is deemed to be too costly. This article argues that rationing is designed into the English NHS and designed out of US Medicare; and compares rationing for the elderly in the United States and in England for acute care, care at the end of life, and chronic care.

In silico methods for design of biological therapeutics.

PubMed

Roy, Ankit; Nair, Sanjana; Sen, Neeladri; Soni, Neelesh; Madhusudhan, M S

2017-12-01

It has been twenty years since the first rationally designed small molecule drug was introduced into the market. Since then, we have progressed from designing small molecules to designing biotherapeutics. This class of therapeutics includes designed proteins, peptides and nucleic acids that could more effectively combat drug resistance and even act in cases where the disease is caused because of a molecular deficiency. Computational methods are crucial in this design exercise and this review discusses the various elements of designing biotherapeutic proteins and peptides. Many of the techniques discussed here, such as the deterministic and stochastic design methods, are generally used in protein design. We have devoted special attention to the design of antibodies and vaccines. In addition to the methods for designing these molecules, we have included a comprehensive list of all biotherapeutics approved for clinical use. Also included is an overview of methods that predict the binding affinity, cell penetration ability, half-life, solubility, immunogenicity and toxicity of the designed therapeutics. Biotherapeutics are only going to grow in clinical importance and are set to herald a new generation of disease management and cure. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Vaccines: From Empirical Development to Rational Design

PubMed Central

Rueckert, Christine; Guzmán, Carlos A.

2012-01-01

Infectious diseases are responsible for an overwhelming number of deaths worldwide and their clinical management is often hampered by the emergence of multi-drug-resistant strains. Therefore, prevention through vaccination currently represents the best course of action to combat them. However, immune escape and evasion by pathogens often render vaccine development difficult. Furthermore, most currently available vaccines were empirically designed. In this review, we discuss why rational design of vaccines is not only desirable but also necessary. We introduce recent developments towards specifically tailored antigens, adjuvants, and delivery systems, and discuss the methodological gaps and lack of knowledge still hampering true rational vaccine design. Finally, we address the potential and limitations of different strategies and technologies for advancing vaccine development. PMID:23144616

The Rationality of Alcoholics Anonymous and the Spirituality of Rational Emotive Behavior Therapy.

ERIC Educational Resources Information Center

Velten, Emmett

1996-01-01

Argues that Alcoholics Anonymous (AA) and Rational Emotive Behavior Therapy (REBT) share important rational objectives and numerous cognitive-behavioral methods. Both emphasize a philosophical shift as a principal ingredient for change. Provides definitions of rationality and spirituality and explains how REBT and smart recovery are spiritual…

A Proposal for the use of the Consortium Method in the Design-build system

NASA Astrophysics Data System (ADS)

Miyatake, Ichiro; Kudo, Masataka; Kawamata, Hiroyuki; Fueta, Toshiharu

In view of the necessity for efficient implementation of public works projects, it is expected to utilize advanced technical skills of private firms, for the purpose of reducing project costs, improving performance and functions of construction objects, and reducing work periods, etc. The design-build system is a method to order design and construction as a single contract, including design of structural forms and main specifications of the construction object. This is a system in which high techniques of private firms can be utilized, as a means to ensure qualities of design and construction, rational design, and efficiency of the project. The objective of this study is to examine the use of a method to form a consortium of civil engineering consultants and construction companies, as it is an issue related to the implementation of the design-build method. Furthermore, by studying various forms of consortiums to be introduced in future, it proposes procedural items required to utilize this method, during the bid and after signing a contract, such as the estimate submission from the civil engineering consultants etc.

Global asymptotic stabilisation of rational dynamical systems based on solving BMI

NASA Astrophysics Data System (ADS)

Esmaili, Farhad; Kamyad, A. V.; Jahed-Motlagh, Mohammad Reza; Pariz, Naser

2017-08-01

In this paper, the global asymptotic stabiliser design of rational systems is studied in detail. To develop the idea, the state equations of the system are transformed to a new coordinate via polynomial transformation and the state feedback control law. This in turn is followed by the satisfaction of the linear growth condition (i.e. Lipschitz at zero). Based on a linear matrix inequality solution, the system in the new coordinate is globally asymptotically stabilised and then, leading to the global asymptotic stabilisation of the primary system. The polynomial transformation coefficients are derived by solving the bilinear matrix inequality problem. To confirm the capability of this method, three examples are highlighted.

An evaluation of a course on the rational use of medication in nursing from the perspective of the students.

PubMed

Unver, Vesile; Başak, Tülay; İyigün, Emine; Taştan, Sevinç; Demiralp, Meral; Yıldız, Dilek; Ayhan, Hatice; Köse, Gülşah; Yüksel, Çiğdem; Çelikel, Ayşegül Soydan; Hatipoglu, Sevgi

2013-11-01

The objectives of educational instruction on the rational use of medication are to teach students about frequent pharmaceutical applications, dosage calculations, observation of adverse side effects and patient training. A simulation project was used in nursing education/medical staff education to effectively gain knowledge and skills. In this study, our first aim was to investigate the effect of using a simulated patient as a teaching method on the performance of students in medication administration. Our second aim was to explore the students' views on the simulated patient teaching method in terms of the skills acquired in administering medication. The study was designed and carried out as a quasi-experimental investigation in Turkey between September 2011 and December 2011. The participants in the study were senior nursing students at a nursing school in Turkey. The data from eighty-five nursing students were obtained both at pretest and posttest. The views of all eighty-two students regarding a course on the rational use of medications were taken into consideration. Simulated patients were used throughout the entire course. An objectively constructed evaluation form (OCEF) was administered both at pretest and posttest to obtain participant feedback on a course on the rational use of medication. Descriptive statistics and a paired sample t-test were used in the data analyses. The mean pre-test score on the evaluation form was 24.02 ± 16.06, whereas the mean post-test score was 54.28 ± 14.54. Therefore, there was a statistically significant difference between the mean pre- and post-test scores (p<0.01; t=14.35). The use of a simulated patient in a course on the rational use of medication proved effective. Furthermore, the students gave positive feedback regarding the use of the simulated patient as a teaching method. Copyright © 2012 Elsevier Ltd. All rights reserved.

A method for estimating peak and time of peak streamflow from excess rainfall for 10- to 640-acre watersheds in the Houston, Texas, metropolitan area

USGS Publications Warehouse

Asquith, William H.; Cleveland, Theodore G.; Roussel, Meghan C.

2011-01-01

Estimates of peak and time of peak streamflow for small watersheds (less than about 640 acres) in a suburban to urban, low-slope setting are needed for drainage design that is cost-effective and risk-mitigated. During 2007-10, the U.S. Geological Survey (USGS), in cooperation with the Harris County Flood Control District and the Texas Department of Transportation, developed a method to estimate peak and time of peak streamflow from excess rainfall for 10- to 640-acre watersheds in the Houston, Texas, metropolitan area. To develop the method, 24 watersheds in the study area with drainage areas less than about 3.5 square miles (2,240 acres) and with concomitant rainfall and runoff data were selected. The method is based on conjunctive analysis of rainfall and runoff data in the context of the unit hydrograph method and the rational method. For the unit hydrograph analysis, a gamma distribution model of unit hydrograph shape (a gamma unit hydrograph) was chosen and parameters estimated through matching of modeled peak and time of peak streamflow to observed values on a storm-by-storm basis. Watershed mean or watershed-specific values of peak and time to peak ("time to peak" is a parameter of the gamma unit hydrograph and is distinct from "time of peak") of the gamma unit hydrograph were computed. Two regression equations to estimate peak and time to peak of the gamma unit hydrograph that are based on watershed characteristics of drainage area and basin-development factor (BDF) were developed. For the rational method analysis, a lag time (time-R), volumetric runoff coefficient, and runoff coefficient were computed on a storm-by-storm basis. Watershed-specific values of these three metrics were computed. A regression equation to estimate time-R based on drainage area and BDF was developed. Overall arithmetic means of volumetric runoff coefficient (0.41 dimensionless) and runoff coefficient (0.25 dimensionless) for the 24 watersheds were used to express the rational method in terms of excess rainfall (the excess rational method). Both the unit hydrograph method and excess rational method are shown to provide similar estimates of peak and time of peak streamflow. The results from the two methods can be combined by using arithmetic means. A nomograph is provided that shows the respective relations between the arithmetic-mean peak and time of peak streamflow to drainage areas ranging from 10 to 640 acres. The nomograph also shows the respective relations for selected BDF ranging from undeveloped to fully developed conditions. The nomograph represents the peak streamflow for 1 inch of excess rainfall based on drainage area and BDF; the peak streamflow for design storms from the nomograph can be multiplied by the excess rainfall to estimate peak streamflow. Time of peak streamflow is readily obtained from the nomograph. Therefore, given excess rainfall values derived from watershed-loss models, which are beyond the scope of this report, the nomograph represents a method for estimating peak and time of peak streamflow for applicable watersheds in the Houston metropolitan area. Lastly, analysis of the relative influence of BDF on peak streamflow is provided, and the results indicate a 0:04log10 cubic feet per second change of peak streamflow per positive unit of change in BDF. This relative change can be used to adjust peak streamflow from the method or other hydrologic methods for a given BDF to other BDF values; example computations are provided.

Concepts and Methods of Explicit Marital Negotiation Training with the Marriage Contract Game.

ERIC Educational Resources Information Center

Blechman, Elaine A.; Rabin, Claire

1982-01-01

Describes the Marriage Contract Game, designed to help couples negotiate relationship and task problems in an explicit, rational manner. Discusses the game's conceptual ties to modes of behavioral family intervention and to the social psychology of bargaining. Concludes with an example of the game's application to a distressed couple. (Author/JAC)

Meeting on Literacy Training, Berlin (West). Final Report. July 11-17, 1975.

ERIC Educational Resources Information Center

International Inst. for Adult Literacy Methods, Teheran (Iran).

This report's major points are highlighted in two sections: Section One sets forth the rational, design, and intended use of the training monograph series, "Literacy in Development", which (1) has been commissioned by the International Institute for Adult Literacy Methods, (2) is to be used as the basis for the Institute's future training…

One-pot synthesis of water soluble iron nanoparticles using rationally-designed peptides and ligand release.

PubMed

Papst, Stefanie; Cheong, Soshan; Banholzer, Moritz J; Brimble, Margaret A; Williams, David E; Tilley, Richard D

2013-05-18

Herein we report the rational design of new phosphopeptides for control of nucleation, growth and aggregation of water-soluble, superparamagnetic iron-iron oxide core-shell nanoparticles. The use of the designed peptides enables a one-pot synthesis that avoids utilizing unstable or toxic iron precursors, organic solvents, and the need for exchange of capping agent after synthesis of the NPs.

Effects of rational emotive occupational health therapy intervention on the perceptions of organizational climate and occupational risk management practices among electronics technology employees in Nigeria

PubMed Central

Ogbuanya, Theresa Chinyere; Eseadi, Chiedu; Orji, Chibueze Tobias; Ede, Moses Onyemaechi; Ohanu, Ifeanyi Benedict; Bakare, Jimoh

2017-01-01

Abstract Background: Improving employees’ perception of organizational climate, and coaching them to remain steadfast when managing occupational risks associated with their job, might have an important effect on their psychosocial wellbeing and occupational health. This study examined the effects of a rational emotive occupational health therapy intervention program on the perceptions of organizational climate and occupational risk management practices. Methods: The participants were 77 electronics technology employees in the south-east of Nigeria. The study used a pretest–posttest control group design. Results: The rational emotive occupational health therapy intervention program significantly improved perceptions of the organizational climate for the people in the treatment group compared to those in the waitlist control group at post-intervention and follow-up assessments. Occupational risk management practices of the employees in the treatment group were also significantly better than those in the waitlist control group at the same 2 assessments. Conclusions: Corporate application of a rational emotive behavior therapy as an occupational health therapy intervention program is essential for improving the perceptions of organizational climate and promoting the adoption of feasible occupational risk management strategies in the workplace. PMID:28471971

Scheduled power tracking control of the wind-storage hybrid system based on the reinforcement learning theory

NASA Astrophysics Data System (ADS)

Li, Ze

2017-09-01

In allusion to the intermittency and uncertainty of the wind electricity, energy storage and wind generator are combined into a hybrid system to improve the controllability of the output power. A scheduled power tracking control method is proposed based on the reinforcement learning theory and Q-learning algorithm. In this method, the state space of the environment is formed with two key factors, i.e. the state of charge of the energy storage and the difference value between the actual wind power and scheduled power, the feasible action is the output power of the energy storage, and the corresponding immediate rewarding function is designed to reflect the rationality of the control action. By interacting with the environment and learning from the immediate reward, the optimal control strategy is gradually formed. After that, it could be applied to the scheduled power tracking control of the hybrid system. Finally, the rationality and validity of the method are verified through simulation examples.

Application of the Quality by Design Approach to the Freezing Step of Freeze-Drying: Building the Design Space.

PubMed

Arsiccio, Andrea; Pisano, Roberto

2018-06-01

The present work shows a rational method for the development of the freezing step of a freeze-drying cycle. The current approach to the selection of freezing conditions is still empirical and nonsystematic, thus resulting in poor robustness of control strategy. The final aim of this work is to fill this gap, describing a rational procedure, based on mathematical modeling, for properly choosing the freezing conditions. Mechanistic models are used for the prediction of temperature profiles during freezing and dimension of ice crystals being formed. Mathematical description of the drying phase of freeze-drying is also coupled with the results obtained by freezing models, thus providing a comprehensive characterization of the lyophilization process. In this framework, deep understanding of the phenomena involved is required, and according to the Quality by Design approach, this knowledge can be used to build the design space. The step-by-step procedure for building the design space for freezing is thus described, and examples of applications are provided. The calculated design space is validated upon experimental data, and we show that it allows easy control of the freezing process and fast selection of appropriate operating conditions. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Rational first integrals of geodesic equations and generalised hidden symmetries

NASA Astrophysics Data System (ADS)

Aoki, Arata; Houri, Tsuyoshi; Tomoda, Kentaro

2016-10-01

We discuss novel generalisations of Killing tensors, which are introduced by considering rational first integrals of geodesic equations. We introduce the notion of inconstructible generalised Killing tensors, which cannot be constructed from ordinary Killing tensors. Moreover, we introduce inconstructible rational first integrals, which are constructed from inconstructible generalised Killing tensors, and provide a method for checking the inconstructibility of a rational first integral. Using the method, we show that the rational first integral of the Collinson-O’Donnell solution is not inconstructible. We also provide several examples of metrics admitting an inconstructible rational first integral in two and four-dimensions, by using the Maciejewski-Przybylska system. Furthermore, we attempt to generalise other hidden symmetries such as Killing-Yano tensors.

Rational design of a dual-mode optical and chemical prodrug.

PubMed

McCoy, Colin P; Rooney, Clare; Jones, David S; Gorman, Sean P; Nieuwenhuyzen, Mark

2007-01-01

The purpose of this study is to demonstrate the rational design and behaviour of the first dual-mode optical and chemical prodrug, exemplified by an acetyl salicylic acid-based system. A cyclic 1,4-benzodioxinone prodrug was synthesised by reaction of 3,5-dimethoxybenzoin and acetyl salicoyl chloride with pyridine. After purification by column chromatography and recrystallization, characterization was achieved using infrared and NMR spectroscopies, mass spectrometry, elemental analysis and single crystal X-ray diffraction. Light-triggered drug liberation was characterised via UV-visible spectroscopy following low-power 365 nm irradiation for controlled times. Chemical drug liberation was characterised via UV-visible spectroscopy in pH 5.5 solution. The synthetic method yielded pure prodrug, with full supporting characterisation. Light-triggered drug liberation proceeded at a rate of 8.30x10(-2) s-1, while chemical, hydrolytic liberation proceeded independently at 1.89x10(-3) s-1. The photochemical and hydrolytic reactions were both quantitative. This study demonstrates the first rational dual-mode optical and chemical prodrug, using acetyl salicylic acid as a model, acting as a paradigm for future dual-mode systems. Photochemical drug liberation proceeds 44 times faster than chemical liberation, suggesting potential use in drug-eluting medical devices where an additional burst of drug is required at the onset of infection.

Rational design of aptazyme riboswitches for efficient control of gene expression in mammalian cells

PubMed Central

Zhong, Guocai; Wang, Haimin; Bailey, Charles C; Gao, Guangping; Farzan, Michael

2016-01-01

Efforts to control mammalian gene expression with ligand-responsive riboswitches have been hindered by lack of a general method for generating efficient switches in mammalian systems. Here we describe a rational-design approach that enables rapid development of efficient cis-acting aptazyme riboswitches. We identified communication-module characteristics associated with aptazyme functionality through analysis of a 32-aptazyme test panel. We then developed a scoring system that predicts an aptazymes’s activity by integrating three characteristics of communication-module bases: hydrogen bonding, base stacking, and distance to the enzymatic core. We validated the power and generality of this approach by designing aptazymes responsive to three distinct ligands, each with markedly wider dynamic ranges than any previously reported. These aptayzmes efficiently regulated adeno-associated virus (AAV)-vectored transgene expression in cultured mammalian cells and mice, highlighting one application of these broadly usable regulatory switches. Our approach enables efficient, protein-independent control of gene expression by a range of small molecules. DOI: http://dx.doi.org/10.7554/eLife.18858.001 PMID:27805569

Milk Production, Physiological Condition and Performance of Etawa Crossbreed Goats Feed by Ration Supplemented with Mangosteen Peel Flour

NASA Astrophysics Data System (ADS)

Dzarnisa; Rachmadi, D.; Azhar, A.; Fakhrur Riza, R.; Hidayati, A.

2018-02-01

Study on the effect of the addition of mangosteen (Garcinia mangostana L.) peel flour on physiological condition and performance of Etawa crossbreed goats was done. This was to grant the use of mangosteen peel flour that rich of antioxidants and has variety good benefits for health as feed additive for cattle. This study used a Complete Randomized Block Design consisting of 4 treatment groups and 4 replications each. Subjects were 16 female Etawa crossbreed goats randomly designed into treatments group based on lactation periods. Subjects were feed with traditional rations (control, A), traditional rations and 2.5% mangosteen peel flour (B), tradition rations and 5% mangosteen peel flour (C), and traditional rations and 7,5 % mangosteen peel flour (D). Data on performance (milk production) and physiological condition (respiratory frequency, rectal temperature, and heart rate) obtained were analyzed using analysis of variance (ANOVA). The results showed that the addition of mangosteen peel flour as food additive in the rations resulted in variations in the milk production, physiological condition (rectal temperature, heart rate and respiration frequency) and performances (daily weigh gain, food consumption, ration conversion and breast volume) of Etawa crossbreed goats, but significant effect was only observed in the respiration frequency. The addition of 2.5% mangosteen peel flour in the ration caused the best, expected effects on milk production physiological condition and performance of Etawa crossbreed goats.

Models for Rational Number Bases

ERIC Educational Resources Information Center

Pedersen, Jean J.; Armbruster, Frank O.

1975-01-01

This article extends number bases to negative integers, then to positive rationals and finally to negative rationals. Methods and rules for operations in positive and negative rational bases greater than one or less than negative one are summarized in tables. Sample problems are explained and illustrated. (KM)

Computerized structural mechanics for 1990's: Advanced aircraft needs

NASA Technical Reports Server (NTRS)

Viswanathan, A. V.; Backman, B. F.

1989-01-01

The needs for computerized structural mechanics (CSM) as seen from the standpoint of the aircraft industry are discussed. These needs are projected into the 1990's with special focus on the new advanced materials. Preliminary design/analysis, research, and detail design/analysis are identified as major areas. The role of local/global analyses in these different areas is discussed. The lessons learned in the past are used as a basis for the design of a CSM framework that could modify and consolidate existing technology and include future developments in a rational and useful way. A philosophy is stated, and a set of analyses needs driven by the emerging advanced composites is enumerated. The roles of NASA, the universities, and the industry are identified. Finally, a set of rational research targets is recommended based on both the new types of computers and the increased complexity the industry faces. Computerized structural mechanics should be more than new methods in structural mechanics and numerical analyses. It should be a set of engineering applications software products that combines innovations in structural mechanics, numerical analysis, data processing, search and display features, and recent hardware advances and is organized in a framework that directly supports the design process.

Nutritional Criteria for Military Rations and Effects of Prolonged Feeding on Acceptability

NASA Technical Reports Server (NTRS)

Schnakenberg, D.

1985-01-01

Broad nutritional policies for operational rations are designed to insure that the nutritional content of the rations served will sustain combat effectiveness. Concern exists that these rations, although nutritionally complete, would become monotonous because of limited variety causing nutrient intake to decrease and body weight losses to occur with adverse effects on morale and combat effectiveness. Whenever possible, troops are now fed one or two hot meals per day containing fresh foods and a much greater variety of foods than are available in packaged rations. A laboratory test was conducted with student volunteers and the results are discussed.

A rational-emotive stress management intervention for reducing job burnout and dysfunctional distress among special education teachers

PubMed Central

Ugwoke, Samuel C.; Eseadi, Chiedu; Onuigbo, Liziana N.; Aye, Eucharia N.; Akaneme, Immaculata N.; Oboegbulem, Angie I.; Ezenwaji, Ifeyinwa O.; Nwobi, Anthonia U.; Nwaubani, Okechukwu O.; Ezegbe, Bernedeth N.; Ede, Moses O.; Orji, Chibueze T.; Onuoha, Joseph C.; Onu, Eucharia U.; Okeke, Francisca; Agu, Patricia; Omeje, Joachim C.; Omeke, Faith; Ugwu, Romanus; Arumede, Florence; Eneh, Annastasia

2018-01-01

Abstract Background: Job-related burnout and distress are adverse stress responses which affect individuals in their occupational environment. This study aimed at investigating the effect of a rational-emotive stress management program on job burnout and dysfunctional distress among special education teachers in Nigeria. Methods: A pretest–posttest randomized control group design was used. The participants in the study were 54 special education teachers. Data were collected using self-report questionnaires. Participants were allocated to either the treatment group (n = 28 [59.1%]) or the waitlist control group (n = 26 [48.1%]), respectively. A rational-emotive stress management manual was used to deliver the intervention. We statistically analyzed the data collected at three-time points with repeated-measures analysis of variance. Results: At baseline, the job-related burnout symptoms and distress scores of participants were high. However, an intention-to-treat analysis showed that the rational-emotive stress management intervention program was efficacious in reducing the levels of job-related burnout symptoms and dysfunctional distress among participants assigned to the treatment group, compared to a waitlisted group at post-treatment and follow-up meetings. Conclusion: Our study demonstrates the effectiveness of a rational-emotive stress management intervention in reducing the level of job-related burnout and distress in a sample of special education teachers in Nigeria. Occupational health counsellors and other clinicians with sufficient knowledge of rational-emotive behavior therapy framework are urged to employ this approach in assisting other employees in managing job burnout symptoms, and distress. PMID:29703004

Cloaking of arbitrarily shaped objects with homogeneous coatings

NASA Astrophysics Data System (ADS)

Forestiere, Carlo; Dal Negro, Luca; Miano, Giovanni

2014-05-01

We present a theory for the cloaking of arbitrarily shaped objects and demonstrate electromagnetic scattering cancellation through designed homogeneous coatings. First, in the small-particle limit, we expand the dipole moment of a coated object in terms of its resonant modes. By zeroing the numerator of the resulting rational function, we accurately predict the permittivity values of the coating layer that abates the total scattered power. Then, we extend the applicability of the method beyond the small-particle limit, deriving the radiation corrections of the scattering-cancellation permittivity within a perturbation approach. Our method permits the design of invisibility cloaks for irregularly shaped devices such as complex sensors and detectors.

Rational Behavior Training: A Seven Lesson Sequence for Teaching Rational Behavior Skills to Students with Social and Emotional Disabilities.

ERIC Educational Resources Information Center

Patton, Patricia Lucey

This seven lesson curriculum sequence is designed to help teachers teach principles of Rational Behavior Training (RBT) which targets thinking behaviors, feeling behaviors, and behavioral responses to the environment. The program is appropriate for students with social and emotional disabilities and also develops reading, writing, spelling,…

Reforming Educator Compensation. The Productivity for Results Series No. 1

ERIC Educational Resources Information Center

Podgursky, Michael

2014-01-01

If a rational system of teacher compensation, aimed at recruiting and retaining high-quality teachers, were designed from scratch, it is unlikely it would bear any resemblance to the system that is currently in place. In this paper, the author takes a deep look into how the method of paying teachers evolved. He shows that compensation systems have…

Diagnosis of the Ill-condition of the RFM Based on Condition Index and Variance Decomposition Proportion (CIVDP)

NASA Astrophysics Data System (ADS)

Qing, Zhou; Weili, Jiao; Tengfei, Long

2014-03-01

The Rational Function Model (RFM) is a new generalized sensor model. It does not need the physical parameters of sensors to achieve a high accuracy that is compatible to the rigorous sensor models. At present, the main method to solve RPCs is the Least Squares Estimation. But when coefficients has a large number or the distribution of the control points is not even, the classical least square method loses its superiority due to the ill-conditioning problem of design matrix. Condition Index and Variance Decomposition Proportion (CIVDP) is a reliable method for diagnosing the multicollinearity among the design matrix. It can not only detect the multicollinearity, but also can locate the parameters and show the corresponding columns in the design matrix. In this paper, the CIVDP method is used to diagnose the ill-condition problem of the RFM and to find the multicollinearity in the normal matrix.

Rational design of new electrolyte materials for electrochemical double layer capacitors

NASA Astrophysics Data System (ADS)

Schütter, Christoph; Husch, Tamara; Viswanathan, Venkatasubramanian; Passerini, Stefano; Balducci, Andrea; Korth, Martin

2016-09-01

The development of new electrolytes is a centerpiece of many strategies to improve electrochemical double layer capacitor (EDLC) devices. We present here a computational screening-based rational design approach to find new electrolyte materials. As an example application, the known chemical space of almost 70 million compounds is investigated in search of electrochemically more stable solvents. Cyano esters are identified as especially promising new compound class. Theoretical predictions are validated with subsequent experimental studies on a selected case. These studies show that based on theoretical predictions only, a previously untested, but very well performing compound class was identified. We thus find that our rational design strategy is indeed able to successfully identify completely new materials with substantially improved properties.

Special Course on Engineering Methods in Aerodynamic Analysis and Design of Aircraft (Les Methodes d’Ingenierie Employee lors de l’Analyse et de la Conception des Aeronefs)

DTIC Science & Technology

1992-01-01

study assumed to the VLM-SA method (solid carve), obtained by combininglie between 15 and 75% of the local wing chord) The ex - the potential-flow...the Consultant and Lxt hange Programme and the Aeroslace Apphations Studies Programme The results oa AGARD work are reported it) the member rations...Testing AGARD CP.429, July 1988 Aerodynamics of Hypersonic, Lifting Vehicles AGARD CP-428, Novemnber 1987 Aerodynamic and Related Hydr dynamic Studies

Rational Thinking in School-Based Practice

ERIC Educational Resources Information Center

Clark, Mary Kristen; Flynn, Perry

2011-01-01

Purpose: We reflect on Alan Kamhi's (2011) prologue on balancing certainty and uncertainty as it pertains to school-based practice. Method: In schools, rational thinking depends on effective team processes, much like professional learning communities. We consider the conditions that are required for rational thinking and how rational team dialogue…

Modeling charge transport in organic photovoltaic materials.

PubMed

Nelson, Jenny; Kwiatkowski, Joe J; Kirkpatrick, James; Frost, Jarvist M

2009-11-17

The performance of an organic photovoltaic cell depends critically on the mobility of charge carriers within the constituent molecular semiconductor materials. However, a complex combination of phenomena that span a range of length and time scales control charge transport in disordered organic semiconductors. As a result, it is difficult to rationalize charge transport properties in terms of material parameters. Until now, efforts to improve charge mobilities in molecular semiconductors have proceeded largely by trial and error rather than through systematic design. However, recent developments have enabled the first predictive simulation studies of charge transport in disordered organic semiconductors. This Account describes a set of computational methods, specifically molecular modeling methods, to simulate molecular packing, quantum chemical calculations of charge transfer rates, and Monte Carlo simulations of charge transport. Using case studies, we show how this combination of methods can reproduce experimental mobilities with few or no fitting parameters. Although currently applied to material systems of high symmetry or well-defined structure, further developments of this approach could address more complex systems such anisotropic or multicomponent solids and conjugated polymers. Even with an approximate treatment of packing disorder, these computational methods simulate experimental mobilities within an order of magnitude at high electric fields. We can both reproduce the relative values of electron and hole mobility in a conjugated small molecule and rationalize those values based on the symmetry of frontier orbitals. Using fully atomistic molecular dynamics simulations of molecular packing, we can quantitatively replicate vertical charge transport along stacks of discotic liquid crystals which vary only in the structure of their side chains. We can reproduce the trends in mobility with molecular weight for self-organizing polymers using a cheap, coarse-grained structural simulation method. Finally, we quantitatively reproduce the field-effect mobility in disordered C60 films. On the basis of these results, we conclude that all of the necessary building blocks are in place for the predictive simulation of charge transport in macromolecular electronic materials and that such methods can be used as a tool toward the future rational design of functional organic electronic materials.

Core/shell PLGA microspheres with controllable in vivo release profile via rational core phase design.

PubMed

Yu, Meiling; Yao, Qing; Zhang, Yan; Chen, Huilin; He, Haibing; Zhang, Yu; Yin, Tian; Tang, Xing; Xu, Hui

2018-02-27

Highly soluble drugs tend to release from preparations at high speeds, which make them need to be taken at frequent intervals. Additionally, some drugs need to be controlled to release in vivo at certain periods, so as to achieve therapeutic effects. Thus, the objective of this study is to design injectable microparticulate systems with controllable in vivo release profile. Biodegradable PLGA was used as the matrix material to fabricate microspheres using the traditional double emulsification-solvent evaporation method as well as improved techniques, with gel (5% gelatine or 25% F127) or LP powders as the inner phases. Their physicochemical properties were systemically investigated. Microspheres prepared by modified methods had an increase in drug loading (15.50, 16.72, 15.66%, respectively) and encapsulation efficiencies (73.46, 79.42, 74.40%, respectively) when compared with traditional methods (12.01 and 57.06%). The morphology of the particles was characterized by optical microscope (OM) and scanning electron microscopy (SEM), and the amorphous nature of the encapsulated drug was confirmed by differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis. To evaluate their release behaviour, the in vitro degradation, in vitro release and in vivo pharmacodynamics were subsequently studied. Traditional microspheres prepared in this study with water as the inner phase had a relatively short release period within 16 d when compared with modified microspheres with 5% gelatine as the inner phase, which resulted in a smooth release profile and appropriate plasma LP concentrations over 21 d. Thus this type of modified microspheres can be better used in drugs requiring sustained release. The other two formulations containing 25% F127 and LP micropowders presented two-stage release profiles, resulting in fluctuant plasma LP concentrations which may be suitable for drugs requiring controlled release. All the results suggested that drug release rates from the microspheres prepared by various methods were mainly controlled by either the porosity inside the microspheres or the degradation of materials, which could, therefore, lead to different release behaviours. This results indicated great potential of the PLGA microsphere formulation as an injectable depot for controllable in vivo release profile via rational core phase design. Core/shell microspheres fabricated by modified double emulsification-solvent evaporation methods, with various inner phases, to obtain high loading drugs system, as well as appropriate release behaviours. Accordingly, control in vivo release profile via rational core phase design.

Proposing water balance method for water availability estimation in Indonesian regional spatial planning

NASA Astrophysics Data System (ADS)

Juniati, A. T.; Sutjiningsih, D.; Soeryantono, H.; Kusratmoko, E.

2018-01-01

The water availability (WA) of a region is one of important consideration in both the formulation of spatial plans and the evaluation of the effectiveness of actual land use in providing sustainable water resources. Information on land-water needs vis-a-vis their availability in a region determines the state of the surplus or deficit to inform effective land use utilization. How to calculate water availability have been described in the Guideline in Determining the Carrying Capacity of the Environment in Regional Spatial Planning. However, the method of determining the supply and demand of water on these guidelines is debatable since the determination of WA in this guideline used a rational method. The rational method is developed the basis for storm drain design practice and it is essentially a peak discharge method peak discharge calculation method. This paper review the literature in methods of water availability estimation which is described descriptively, and present arguments to claim that water balance method is a more fundamental and appropriate tool in water availability estimation. A better water availability estimation method would serve to improve the practice in preparing formulations of Regional Spatial Plan (RSP) as well as evaluating land use capacity in providing sustainable water resources.

Does rational selection of training and test sets improve the outcome of QSAR modeling?

PubMed

Martin, Todd M; Harten, Paul; Young, Douglas M; Muratov, Eugene N; Golbraikh, Alexander; Zhu, Hao; Tropsha, Alexander

2012-10-22

Prior to using a quantitative structure activity relationship (QSAR) model for external predictions, its predictive power should be established and validated. In the absence of a true external data set, the best way to validate the predictive ability of a model is to perform its statistical external validation. In statistical external validation, the overall data set is divided into training and test sets. Commonly, this splitting is performed using random division. Rational splitting methods can divide data sets into training and test sets in an intelligent fashion. The purpose of this study was to determine whether rational division methods lead to more predictive models compared to random division. A special data splitting procedure was used to facilitate the comparison between random and rational division methods. For each toxicity end point, the overall data set was divided into a modeling set (80% of the overall set) and an external evaluation set (20% of the overall set) using random division. The modeling set was then subdivided into a training set (80% of the modeling set) and a test set (20% of the modeling set) using rational division methods and by using random division. The Kennard-Stone, minimal test set dissimilarity, and sphere exclusion algorithms were used as the rational division methods. The hierarchical clustering, random forest, and k-nearest neighbor (kNN) methods were used to develop QSAR models based on the training sets. For kNN QSAR, multiple training and test sets were generated, and multiple QSAR models were built. The results of this study indicate that models based on rational division methods generate better statistical results for the test sets than models based on random division, but the predictive power of both types of models are comparable.

Semantics and technologies in modern design of interior stairs

NASA Astrophysics Data System (ADS)

Kukhta, M.; Sokolov, A.; Pelevin, E.

2015-10-01

Use of metal in the design of interior stairs presents new features for shaping, and can be implemented using different technologies. The article discusses the features of design and production technologies of forged metal spiral staircase considering the image semantics based on the historical and cultural heritage. To achieve the objective was applied structural- semantic method (to identify the organization of structure and semantic features of the artistic image), engineering methods (to justify the construction of the object), anthropometry method and ergonomics (to provide usability), methods of comparative analysis (to reveale the features of the way the ladder in different periods of culture). According to the research results are as follows. Was revealed the semantics influence on the design of interior staircase that is based on the World Tree image. Also was suggested rational calculation of steps to ensure the required strength. And finally was presented technology, providing the realization of the artistic image. In the practical part of the work is presented version of forged staircase.

Improvement of Biocatalysts for Industrial and Environmental Purposes by Saturation Mutagenesis

PubMed Central

Valetti, Francesca; Gilardi, Gianfranco

2013-01-01

Laboratory evolution techniques are becoming increasingly widespread among protein engineers for the development of novel and designed biocatalysts. The palette of different approaches ranges from complete randomized strategies to rational and structure-guided mutagenesis, with a wide variety of costs, impacts, drawbacks and relevance to biotechnology. A technique that convincingly compromises the extremes of fully randomized vs. rational mutagenesis, with a high benefit/cost ratio, is saturation mutagenesis. Here we will present and discuss this approach in its many facets, also tackling the issue of randomization, statistical evaluation of library completeness and throughput efficiency of screening methods. Successful recent applications covering different classes of enzymes will be presented referring to the literature and to research lines pursued in our group. The focus is put on saturation mutagenesis as a tool for designing novel biocatalysts specifically relevant to production of fine chemicals for improving bulk enzymes for industry and engineering technical enzymes involved in treatment of waste, detoxification and production of clean energy from renewable sources. PMID:24970191

An Old Story in the Parallel Synthesis World: An Approach to Hydantoin Libraries.

PubMed

Bogolubsky, Andrey V; Moroz, Yurii S; Savych, Olena; Pipko, Sergey; Konovets, Angelika; Platonov, Maxim O; Vasylchenko, Oleksandr V; Hurmach, Vasyl V; Grygorenko, Oleksandr O

2018-01-08

An approach to the parallel synthesis of hydantoin libraries by reaction of in situ generated 2,2,2-trifluoroethylcarbamates and α-amino esters was developed. To demonstrate utility of the method, a library of 1158 hydantoins designed according to the lead-likeness criteria (MW 200-350, cLogP 1-3) was prepared. The success rate of the method was analyzed as a function of physicochemical parameters of the products, and it was found that the method can be considered as a tool for lead-oriented synthesis. A hydantoin-bearing submicromolar primary hit acting as an Aurora kinase A inhibitor was discovered with a combination of rational design, parallel synthesis using the procedures developed, in silico and in vitro screenings.

Does an outcome-based approach to continuing medical education improve physicians' competences in rational prescribing?

PubMed

Esmaily, Hamideh M; Savage, Carl; Vahidi, Rezagoli; Amini, Abolghasem; Dastgiri, Saeed; Hult, Hakan; Dahlgren, Lars Owe; Wahlstrom, Rolf

2009-11-01

Continuing medical education (CME) is compulsory in Iran, and traditionally it is lecture-based, which is mostly not successful. Outcome-based education has been proposed for CME programs. To evaluate the effectiveness of an outcome-based educational intervention with a new approach based on outcomes and aligned teaching methods, on knowledge and skills of general physicians (GPs) working in primary care compared with a concurrent CME program in the field of "Rational prescribing". The method used was cluster randomized controlled design. All GPs working in six cities in one province in Iran were invited to participate. The cities were matched and randomly divided into an intervention arm for education on rational prescribing with an outcome-based approach, and a control arm for a traditional program on the same topic. Knowledge and skills were assessed using a pre- and post-test, including case scenarios. In total, 112 GPs participated. There were significant improvements in knowledge and prescribing skills after the training in the intervention arm as well as in comparison with the changes in the control arm. The overall intervention effect was 26 percentage units. The introduction of an outcome-based approach in CME appears to be effective when creating programs to improve GPs' knowledge and skills.

The secret art of managing healthcare expenses: investigating implicit rationing and autonomy in public healthcare systems.

PubMed

Lauridsen, S M R; Norup, M S; Rossel, P J H

2007-12-01

Rationing healthcare is a difficult task, which includes preventing patients from accessing potentially beneficial treatments. Proponents of implicit rationing argue that politicians cannot resist pressure from strong patient groups for treatments and conclude that physicians should ration without informing patients or the public. The authors subdivide this specific programme of implicit rationing, or "hidden rationing", into local hidden rationing, unsophisticated global hidden rationing and sophisticated global hidden rationing. They evaluate the appropriateness of these methods of rationing from the perspectives of individual and political autonomy and conclude that local hidden rationing and unsophisticated global hidden rationing clearly violate patients' individual autonomy, that is, their right to participate in medical decision-making. While sophisticated global hidden rationing avoids this charge, the authors point out that it nonetheless violates the political autonomy of patients, that is, their right to engage in public affairs as citizens. A defence of any of the forms of hidden rationing is therefore considered to be incompatible with a defence of autonomy.

Computational Prediction of Neutralization Epitopes Targeted by Human Anti-V3 HIV Monoclonal Antibodies

PubMed Central

Shmelkov, Evgeny; Krachmarov, Chavdar; Grigoryan, Arsen V.; Pinter, Abraham; Statnikov, Alexander; Cardozo, Timothy

2014-01-01

The extreme diversity of HIV-1 strains presents a formidable challenge for HIV-1 vaccine design. Although antibodies (Abs) can neutralize HIV-1 and potentially protect against infection, antibodies that target the immunogenic viral surface protein gp120 have widely variable and poorly predictable cross-strain reactivity. Here, we developed a novel computational approach, the Method of Dynamic Epitopes, for identification of neutralization epitopes targeted by anti-HIV-1 monoclonal antibodies (mAbs). Our data demonstrate that this approach, based purely on calculated energetics and 3D structural information, accurately predicts the presence of neutralization epitopes targeted by V3-specific mAbs 2219 and 447-52D in any HIV-1 strain. The method was used to calculate the range of conservation of these specific epitopes across all circulating HIV-1 viruses. Accurately identifying an Ab-targeted neutralization epitope in a virus by computational means enables easy prediction of the breadth of reactivity of specific mAbs across the diversity of thousands of different circulating HIV-1 variants and facilitates rational design and selection of immunogens mimicking specific mAb-targeted epitopes in a multivalent HIV-1 vaccine. The defined epitopes can also be used for the purpose of epitope-specific analyses of breakthrough sequences recorded in vaccine clinical trials. Thus, our study is a prototype for a valuable tool for rational HIV-1 vaccine design. PMID:24587168

Rational Design of Plasmonic Nanoparticles for Enhanced Cavitation and Cell Perforation.

PubMed

Lachaine, Rémi; Boutopoulos, Christos; Lajoie, Pierre-Yves; Boulais, Étienne; Meunier, Michel

2016-05-11

Metallic nanoparticles are routinely used as nanoscale antenna capable of absorbing and converting photon energy with subwavelength resolution. Many applications, notably in nanomedicine and nanobiotechnology, benefit from the enhanced optical properties of these materials, which can be exploited to image, damage, or destroy targeted cells and subcellular structures with unprecedented precision. Modern inorganic chemistry enables the synthesis of a large library of nanoparticles with an increasing variety of shapes, composition, and optical characteristic. However, identifying and tailoring nanoparticles morphology to specific applications remains challenging and limits the development of efficient nanoplasmonic technologies. In this work, we report a strategy for the rational design of gold plasmonic nanoshells (AuNS) for the efficient ultrafast laser-based nanoscale bubble generation and cell membrane perforation, which constitute one of the most crucial challenges toward the development of effective gene therapy treatments. We design an in silico rational design framework that we use to tune AuNS morphology to simultaneously optimize for the reduction of the cavitation threshold while preserving the particle structural integrity. Our optimization procedure yields optimal AuNS that are slightly detuned compared to their plasmonic resonance conditions with an optical breakdown threshold 30% lower than randomly selected AuNS and 13% lower compared to similarly optimized gold nanoparticles (AuNP). This design strategy is validated using time-resolved bubble spectroscopy, shadowgraphy imaging and electron microscopy that confirm the particle structural integrity and a reduction of 51% of the cavitation threshold relative to optimal AuNP. Rationally designed AuNS are finally used to perforate cancer cells with an efficiency of 61%, using 33% less energy compared to AuNP, which demonstrate that our rational design framework is readily transferable to a cell environment. The methodology developed here thus provides a general strategy for the systematic design of nanoparticles for nanomedical applications and should be broadly applicable to bioimaging and cell nanosurgery.

Automated selection of stabilizing mutations in designed and natural proteins.

PubMed

Borgo, Benjamin; Havranek, James J

2012-01-31

The ability to engineer novel protein folds, conformations, and enzymatic activities offers enormous potential for the development of new protein therapeutics and biocatalysts. However, many de novo and redesigned proteins exhibit poor hydrophobic packing in their predicted structures, leading to instability or insolubility. The general utility of rational, structure-based design would greatly benefit from an improved ability to generate well-packed conformations. Here we present an automated protocol within the RosettaDesign framework that can identify and improve poorly packed protein cores by selecting a series of stabilizing point mutations. We apply our method to previously characterized designed proteins that exhibited a decrease in stability after a full computational redesign. We further demonstrate the ability of our method to improve the thermostability of a well-behaved native protein. In each instance, biophysical characterization reveals that we were able to stabilize the original proteins against chemical and thermal denaturation. We believe our method will be a valuable tool for both improving upon designed proteins and conferring increased stability upon native proteins.

Automated selection of stabilizing mutations in designed and natural proteins

PubMed Central

Borgo, Benjamin; Havranek, James J.

2012-01-01

The ability to engineer novel protein folds, conformations, and enzymatic activities offers enormous potential for the development of new protein therapeutics and biocatalysts. However, many de novo and redesigned proteins exhibit poor hydrophobic packing in their predicted structures, leading to instability or insolubility. The general utility of rational, structure-based design would greatly benefit from an improved ability to generate well-packed conformations. Here we present an automated protocol within the RosettaDesign framework that can identify and improve poorly packed protein cores by selecting a series of stabilizing point mutations. We apply our method to previously characterized designed proteins that exhibited a decrease in stability after a full computational redesign. We further demonstrate the ability of our method to improve the thermostability of a well-behaved native protein. In each instance, biophysical characterization reveals that we were able to stabilize the original proteins against chemical and thermal denaturation. We believe our method will be a valuable tool for both improving upon designed proteins and conferring increased stability upon native proteins. PMID:22307603

Principles of Protein Stability and Their Application in Computational Design.

PubMed

Goldenzweig, Adi; Fleishman, Sarel

2018-01-26

Proteins are increasingly used in basic and applied biomedical research.Many proteins, however, are only marginally stable and can be expressed in limited amounts, thus hampering research and applications. Research has revealed the thermodynamic, cellular, and evolutionary principles and mechanisms that underlie marginal stability. With this growing understanding, computational stability design methods have advanced over the past two decades starting from methods that selectively addressed only some aspects of marginal stability. Current methods are more general and, by combining phylogenetic analysis with atomistic design, have shown drastic improvements in solubility, thermal stability, and aggregation resistance while maintaining the protein's primary molecular activity. Stability design is opening the way to rational engineering of improved enzymes, therapeutics, and vaccines and to the application of protein design methodology to large proteins and molecular activities that have proven challenging in the past. Expected final online publication date for the Annual Review of Biochemistry Volume 87 is June 20, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Transforming Multidisciplinary Customer Requirements to Product Design Specifications

NASA Astrophysics Data System (ADS)

Ma, Xiao-Jie; Ding, Guo-Fu; Qin, Sheng-Feng; Li, Rong; Yan, Kai-Yin; Xiao, Shou-Ne; Yang, Guang-Wu

2017-09-01

With the increasing of complexity of complex mechatronic products, it is necessary to involve multidisciplinary design teams, thus, the traditional customer requirements modeling for a single discipline team becomes difficult to be applied in a multidisciplinary team and project since team members with various disciplinary backgrounds may have different interpretations of the customers' requirements. A new synthesized multidisciplinary customer requirements modeling method is provided for obtaining and describing the common understanding of customer requirements (CRs) and more importantly transferring them into a detailed and accurate product design specifications (PDS) to interact with different team members effectively. A case study of designing a high speed train verifies the rationality and feasibility of the proposed multidisciplinary requirement modeling method for complex mechatronic product development. This proposed research offersthe instruction to realize the customer-driven personalized customization of complex mechatronic product.

Structure and Computation in Immunoreagent Design: From Diagnostics to Vaccines.

PubMed

Gourlay, Louise; Peri, Claudio; Bolognesi, Martino; Colombo, Giorgio

2017-12-01

Novel immunological tools for efficient diagnosis and treatment of emerging infections are urgently required. Advances in the diagnostic and vaccine development fields are continuously progressing, with reverse vaccinology and structural vaccinology (SV) methods for antigen identification and structure-based antigen (re)design playing increasingly relevant roles. SV, in particular, is predicted to be the front-runner in the future development of diagnostics and vaccines targeting challenging diseases such as AIDS and cancer. We review state-of-the-art methodologies for structure-based epitope identification and antigen design, with specific applicative examples. We highlight the implications of such methods for the engineering of biomolecules with improved immunological properties, potential diagnostic and/or therapeutic uses, and discuss the perspectives of structure-based rational design for the production of advanced immunoreagents. Copyright © 2017 Elsevier Ltd. All rights reserved.

Suicide: Rationality and Responsibility for Life

PubMed Central

Ho, Angela Onkay

2014-01-01

Objectives: Death by suicide is widely held as an undesirable outcome. Most Western countries place emphasis on patient autonomy, a concept of controversy in relation to suicide. This paper explores the tensions between patients’ rights and many societies’ overarching desire to prevent suicide, while clarifying the relations between mental disorders, mental capacity, and rational suicide. Methods: A literature search was conducted using search terms of suicide and ethics in the PubMed and LexisNexis Academic databases. Article titles and abstracts were reviewed and deemed relevant if the paper addressed topics of rational suicide, patient autonomy or rights, or responsibility for life. Further articles were found from reference lists and by suggestion from preliminary reviewers of this paper. Results: Suicidal behaviour in a person cannot be reliably predicted, yet various associations and organizations have developed standards of care for managing patients exhibiting suicidal behaviour. The responsibility for preventing suicide tends to be placed on the treating clinician. In cases where a person is capable of making treatment decisions—uninfluenced by any mental disorder—there is growing interest in the concept of rational suicide. Conclusions: There is much debate about whether suicide can ever be rational. Designating suicide as an undesirable event that should never occur raises the debate of who is responsible for one’s life and runs the risk of erroneously attributing blame for suicide. While upholding patient rights of autonomy in psychiatric care is laudable, cases of suicidality warrant a delicate consideration of clinical judgment, duty of care, and legal obligations. PMID:24881162

Understanding significant processes during work environment interventions to alleviate time pressure and associated sick leave of home care workers – a case study

PubMed Central

2013-01-01

Background Ergonomic and work stress interventions rarely show long-term positive effect. The municipality participating in this study received orders from the Norwegian Labour Inspectorate due to an identified unhealthy level of time pressure, and responded by effectuating several work environment interventions. The study aim is to identify critical factors in the interaction between work environment interventions and independent rationalization measures in order to understand a potential negative interfering effect from concurrent rationalizations on a comprehensive work environment intervention. Methods The study, using a historic prospective mixed-method design, comprised 6 home care units in a municipality in Norway (138 respondents, response rate 76.2%; 17 informants). The study included quantitative estimations, register data of sick leave, a time line of significant events and changes, and qualitative descriptions of employee appraisals of their work situation gathered through semi-structured interviews and open survey responses. Results The work environment interventions were in general regarded as positive by the home care workers. However, all units were simultaneously subjected to substantial contextual instability, involving new work programs, new technology, restructurings, unit mergers, and management replacements, perceived by the home care workers to be major sources of stress. Findings suggest that concurrent changes induced through rationalization resulted in negative exposure effects that negated positive work environment intervention effects, causing an overall deteriorated work situation for the home care workers. Conclusions Establishment and active utilization of communication channels from workers to managers are recommended in order to increase awareness of putative harmful and interruptive effects of rationalization measures. PMID:24238560

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

PubMed

Toyoda, Tetsuro

2011-01-01

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

Program Synthesizes UML Sequence Diagrams

NASA Technical Reports Server (NTRS)

Barry, Matthew R.; Osborne, Richard N.

2006-01-01

A computer program called "Rational Sequence" generates Universal Modeling Language (UML) sequence diagrams of a target Java program running on a Java virtual machine (JVM). Rational Sequence thereby performs a reverse engineering function that aids in the design documentation of the target Java program. Whereas previously, the construction of sequence diagrams was a tedious manual process, Rational Sequence generates UML sequence diagrams automatically from the running Java code.

Development and Validation of HPLC-DAD and UHPLC-DAD Methods for the Simultaneous Determination of Guanylhydrazone Derivatives Employing a Factorial Design.

PubMed

Azevedo de Brito, Wanessa; Gomes Dantas, Monique; Andrade Nogueira, Fernando Henrique; Ferreira da Silva-Júnior, Edeildo; Xavier de Araújo-Júnior, João; Aquino, Thiago Mendonça de; Adélia Nogueira Ribeiro, Êurica; da Silva Solon, Lilian Grace; Soares Aragão, Cícero Flávio; Barreto Gomes, Ana Paula

2017-08-30

Guanylhydrazones are molecules with great pharmacological potential in various therapeutic areas, including antitumoral activity. Factorial design is an excellent tool in the optimization of a chromatographic method, because it is possible quickly change factors such as temperature, mobile phase composition, mobile phase pH, column length, among others to establish the optimal conditions of analysis. The aim of the present work was to develop and validate a HPLC and UHPLC methods for the simultaneous determination of guanylhydrazones with anticancer activity employing experimental design. Precise, exact, linear and robust HPLC and UHPLC methods were developed and validated for the simultaneous quantification of the guanylhydrazones LQM10, LQM14, and LQM17. The UHPLC method was more economic, with a four times less solvent consumption, and 20 times less injection volume, what allowed better column performance. Comparing the empirical approach employed in the HPLC method development to the DoE approach employed in the UHPLC method development, we can conclude that the factorial design made the method development faster, more practical and rational. This resulted in methods that can be employed in the analysis, evaluation and quality control of these new synthetic guanylhydrazones.

Approximation Methods in Multidimensional Filter Design and Related Problems Encountered in Multidimensional System Design.

DTIC Science & Technology

1983-03-21

zero , it is necessary that B M(0) be nonzero. In the case considered here, B M(0) is taken to be nonsingula and withot loss of generality it may be set...452. (c.51 D. Levin, " General order Padd type rational approximants defined from a double power series," J. Inst. Maths. Applics., 18, 1976, pp. 1-8...common zeros in the closed unit bidisc, U- 2 . The 2-D setting provides a nice theoretical framework for generalization of these stabilization results to

Meta-modelling, visualization and emulation of multi-dimensional data for virtual production intelligence

NASA Astrophysics Data System (ADS)

Schulz, Wolfgang; Hermanns, Torsten; Al Khawli, Toufik

2017-07-01

Decision making for competitive production in high-wage countries is a daily challenge where rational and irrational methods are used. The design of decision making processes is an intriguing, discipline spanning science. However, there are gaps in understanding the impact of the known mathematical and procedural methods on the usage of rational choice theory. Following Benjamin Franklin's rule for decision making formulated in London 1772, he called "Prudential Algebra" with the meaning of prudential reasons, one of the major ingredients of Meta-Modelling can be identified finally leading to one algebraic value labelling the results (criteria settings) of alternative decisions (parameter settings). This work describes the advances in Meta-Modelling techniques applied to multi-dimensional and multi-criterial optimization by identifying the persistence level of the corresponding Morse-Smale Complex. Implementations for laser cutting and laser drilling are presented, including the generation of fast and frugal Meta-Models with controlled error based on mathematical model reduction Reduced Models are derived to avoid any unnecessary complexity. Both, model reduction and analysis of multi-dimensional parameter space are used to enable interactive communication between Discovery Finders and Invention Makers. Emulators and visualizations of a metamodel are introduced as components of Virtual Production Intelligence making applicable the methods of Scientific Design Thinking and getting the developer as well as the operator more skilled.

Rational design of therapeutic mAbs against aggregation through protein engineering and incorporation of glycosylation motifs applied to bevacizumab.

PubMed

Courtois, Fabienne; Agrawal, Neeraj J; Lauer, Timothy M; Trout, Bernhardt L

2016-01-01

The aggregation of biotherapeutics is a major hindrance to the development of successful drug candidates; however, the propensity to aggregate is often identified too late in the development phase to permit modification to the protein's sequence. Incorporating rational design for the stability of proteins in early discovery has numerous benefits. We engineered out aggregation-prone regions on the Fab domain of a therapeutic monoclonal antibody, bevacizumab, to rationally design a biobetter drug candidate. With the purpose of stabilizing bevacizumab with respect to aggregation, 2 strategies were undertaken: single point mutations of aggregation-prone residues and engineering a glycosylation site near aggregation-prone residues to mask these residues with a carbohydrate moiety. Both of these approaches lead to comparable decreases in aggregation, with an up to 4-fold reduction in monomer loss. These single mutations and the new glycosylation pattern of the Fab domain do not modify binding to the target. Biobetters with increased stability against aggregation can therefore be generated in a rational manner, by either removing or masking the aggregation-prone region or crowding out protein-protein interactions.

Rational design of carbon and TiO2 assembly materials: covered or strewn, which is better for photocatalysis?

PubMed

Cui, Guan-wei; Wang, Wei-liang; Ma, Ming-yue; Zhang, Ming; Xia, Xin-yuan; Han, Feng-yun; Shi, Xi-feng; Zhao, Ying-qiang; Dong, Yu-bin; Tang, Bo

2013-07-21

The rational design of carbonaceous hybrid nanostructures is very important for obtaining high photoactivity. TiO2 particles strewn with an optimal quantity of carbon nanodots have a much higher photoactivity than that of TiO2 covered with a carbon layer, showing the importance of carbon morphology in the photocatalysis of carbonaceous hybrid nanostructures.

Structure-based engineering of a pectate lyase with improved specific activity for ramie degumming.

PubMed

Zhou, Zhanping; Liu, Yang; Chang, Zhenying; Wang, Huilin; Leier, André; Marquez-Lago, Tatiana T; Ma, Yanhe; Li, Jian; Song, Jiangning

2017-04-01

Biotechnological applications of microbial pectate lyases (Pels) in plant fiber processing are promising, eco-friendly substitutes for conventional chemical degumming processes. However, to potentiate the enzymes' use for industrial applications, resolving the molecular structure to elucidate catalytic mechanisms becomes necessary. In this manuscript, we report the high resolution (1.45 Å) crystal structure of pectate lyase (pelN) from Paenibacillus sp. 0602 in apo form. Through sequence alignment and structural superposition with other members of the polysaccharide lyase (PL) family 1 (PL1), we determined that pelN shares the characteristic right-handed β-helix and is structurally similar to other members of the PL1 family, while exhibiting key differences in terms of catalytic and substrate binding residues. Then, based on information from structure alignments with other PLs, we engineered a novel pelN. Our rational design yielded a pelN mutant with a temperature for enzymatic activity optimally shifted from 67.5 to 60 °C. Most importantly, this pelN mutant displayed both higher specific activity and ramie fiber degumming ability when compared with the wild-type enzyme. Altogether, our rational design method shows great potential for industrial applications. Moreover, we expect the reported high-resolution crystal structure to provide a solid foundation for future rational, structure-based engineering of genetically enhanced pelNs.

Correlating Reactivity and Selectivity to Cyclopentadienyl Ligand Properties in Rh(III)-Catalyzed C-H Activation Reactions: An Experimental and Computational Study.

PubMed

Piou, Tiffany; Romanov-Michailidis, Fedor; Romanova-Michaelides, Maria; Jackson, Kelvin E; Semakul, Natthawat; Taggart, Trevor D; Newell, Brian S; Rithner, Christopher D; Paton, Robert S; Rovis, Tomislav

2017-01-25

Cp X Rh(III)-catalyzed C-H functionalization reactions are a proven method for the efficient assembly of small molecules. However, rationalization of the effects of cyclopentadienyl (Cp X ) ligand structure on reaction rate and selectivity has been viewed as a black box, and a truly systematic study is lacking. Consequently, predicting the outcomes of these reactions is challenging because subtle variations in ligand structure can cause notable changes in reaction behavior. A predictive tool is, nonetheless, of considerable value to the community as it would greatly accelerate reaction development. Designing a data set in which the steric and electronic properties of the Cp X Rh(III) catalysts were systematically varied allowed us to apply multivariate linear regression algorithms to establish correlations between these catalyst-based descriptors and the regio-, diastereoselectivity, and rate of model reactions. This, in turn, led to the development of quantitative predictive models that describe catalyst performance. Our newly described cone angles and Sterimol parameters for Cp X ligands served as highly correlative steric descriptors in the regression models. Through rational design of training and validation sets, key diastereoselectivity outliers were identified. Computations reveal the origins of the outstanding stereoinduction displayed by these outliers. The results are consistent with partial η 5 -η 3 ligand slippage that occurs in the transition state of the selectivity-determining step. In addition to the instructive value of our study, we believe that the insights gained are transposable to other group 9 transition metals and pave the way toward rational design of C-H functionalization catalysts.

Selective host molecules obtained by dynamic adaptive chemistry.

PubMed

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

2014-02-17

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

Beta-function B-spline smoothing on triangulations

NASA Astrophysics Data System (ADS)

Dechevsky, Lubomir T.; Zanaty, Peter

2013-03-01

In this work we investigate a novel family of Ck-smooth rational basis functions on triangulations for fitting, smoothing, and denoising geometric data. The introduced basis function is closely related to a recently introduced general method introduced in utilizing generalized expo-rational B-splines, which provides Ck-smooth convex resolutions of unity on very general disjoint partitions and overlapping covers of multidimensional domains with complex geometry. One of the major advantages of this new triangular construction is its locality with respect to the star-1 neighborhood of the vertex on which the said base is providing Hermite interpolation. This locality of the basis functions can be in turn utilized in adaptive methods, where, for instance a local refinement of the underlying triangular mesh affects only the refined domain, whereas, in other method one needs to investigate what changes are occurring outside of the refined domain. Both the triangular and the general smooth constructions have the potential to become a new versatile tool of Computer Aided Geometric Design (CAGD), Finite and Boundary Element Analysis (FEA/BEA) and Iso-geometric Analysis (IGA).

Information and Entropy

NASA Astrophysics Data System (ADS)

Caticha, Ariel

2007-11-01

What is information? Is it physical? We argue that in a Bayesian theory the notion of information must be defined in terms of its effects on the beliefs of rational agents. Information is whatever constrains rational beliefs and therefore it is the force that induces us to change our minds. This problem of updating from a prior to a posterior probability distribution is tackled through an eliminative induction process that singles out the logarithmic relative entropy as the unique tool for inference. The resulting method of Maximum relative Entropy (ME), which is designed for updating from arbitrary priors given information in the form of arbitrary constraints, includes as special cases both MaxEnt (which allows arbitrary constraints) and Bayes' rule (which allows arbitrary priors). Thus, ME unifies the two themes of these workshops—the Maximum Entropy and the Bayesian methods—into a single general inference scheme that allows us to handle problems that lie beyond the reach of either of the two methods separately. I conclude with a couple of simple illustrative examples.

Transport of Nitric Oxide (NO) in Various Biomedical grade Polyurethanes: Measurements and Modeling Impact on NO Release Properties of Medical Devices

PubMed Central

2016-01-01

Nitric oxide (NO) releasing polymers are promising in improving the biocompatibility of medical devices. Polyurethanes are commonly used to prepare/fabricate many devices (e.g., catheters); however, the transport properties of NO within different polyurethanes are less studied, creating a gap in the rational design of new NO releasing devices involving polyurethane materials. Herein, we study the diffusion and partitioning of NO in different biomedical polyurethanes via the time-lag method. The diffusion of NO is positively correlated with the PDMS content within the polyurethanes, which can be rationalized by effective media theory considering various microphase morphologies. Using catheters as a model device, the effect of these transport properties on the NO release profiles and the distribution around an asymmetric dual lumen catheter are simulated using finite element analysis and validated experimentally. This method can be readily applied in studying other NO release medical devices with different configurations. PMID:27660819

Chairside multi-unit restoration of a quadrant using the new Cerec 3D software.

PubMed

Ender, A; Wiedhahn, K; Mörmann, W H

2003-01-01

The new Cerec 3D design software for inlays and partial and full crowns simplifies work when producing several restorations in one session. Quite significant progress has been achieved, in that the entire row of teeth of a quadrant can be acquired completely and displayed by successively overlapping optical impressions. The digital working model of a quadrant in which all preparations are acquired is the result. The restorations can be designed individually and inserted virtually. Thanks to virtual insertion, the proximal contacts to neighboring restorations can be designed perfectly and all restorations finally designed, milled, and inserted in one sitting. This method provides a significant rationalization effect.

Molecular beacon sequence design algorithm.

PubMed

Monroe, W Todd; Haselton, Frederick R

2003-01-01

A method based on Web-based tools is presented to design optimally functioning molecular beacons. Molecular beacons, fluorogenic hybridization probes, are a powerful tool for the rapid and specific detection of a particular nucleic acid sequence. However, their synthesis costs can be considerable. Since molecular beacon performance is based on its sequence, it is imperative to rationally design an optimal sequence before synthesis. The algorithm presented here uses simple Microsoft Excel formulas and macros to rank candidate sequences. This analysis is carried out using mfold structural predictions along with other free Web-based tools. For smaller laboratories where molecular beacons are not the focus of research, the public domain algorithm described here may be usefully employed to aid in molecular beacon design.

MIST - MINIMUM-STATE METHOD FOR RATIONAL APPROXIMATION OF UNSTEADY AERODYNAMIC FORCE COEFFICIENT MATRICES

NASA Technical Reports Server (NTRS)

Karpel, M.

1994-01-01

Various control analysis, design, and simulation techniques of aeroservoelastic systems require the equations of motion to be cast in a linear, time-invariant state-space form. In order to account for unsteady aerodynamics, rational function approximations must be obtained to represent them in the first order equations of the state-space formulation. A computer program, MIST, has been developed which determines minimum-state approximations of the coefficient matrices of the unsteady aerodynamic forces. The Minimum-State Method facilitates the design of lower-order control systems, analysis of control system performance, and near real-time simulation of aeroservoelastic phenomena such as the outboard-wing acceleration response to gust velocity. Engineers using this program will be able to calculate minimum-state rational approximations of the generalized unsteady aerodynamic forces. Using the Minimum-State formulation of the state-space equations, they will be able to obtain state-space models with good open-loop characteristics while reducing the number of aerodynamic equations by an order of magnitude more than traditional approaches. These low-order state-space mathematical models are good for design and simulation of aeroservoelastic systems. The computer program, MIST, accepts tabular values of the generalized aerodynamic forces over a set of reduced frequencies. It then determines approximations to these tabular data in the LaPlace domain using rational functions. MIST provides the capability to select the denominator coefficients in the rational approximations, to selectably constrain the approximations without increasing the problem size, and to determine and emphasize critical frequency ranges in determining the approximations. MIST has been written to allow two types data weighting options. The first weighting is a traditional normalization of the aerodynamic data to the maximum unit value of each aerodynamic coefficient. The second allows weighting the importance of different tabular values in determining the approximations based upon physical characteristics of the system. Specifically, the physical weighting capability is such that each tabulated aerodynamic coefficient, at each reduced frequency value, is weighted according to the effect of an incremental error of this coefficient on aeroelastic characteristics of the system. In both cases, the resulting approximations yield a relatively low number of aerodynamic lag states in the subsequent state-space model. MIST is written in ANSI FORTRAN 77 for DEC VAX series computers running VMS. It requires approximately 1Mb of RAM for execution. The standard distribution medium for this package is a 9-track 1600 BPI magnetic tape in DEC VAX FILES-11 format. It is also available on a TK50 tape cartridge in DEC VAX BACKUP format. MIST was developed in 1991. DEC VAX and VMS are trademarks of Digital Equipment Corporation. FORTRAN 77 is a registered trademark of Lahey Computer Systems, Inc.

A New Approach to Extreme Value Estimation Applicable to a Wide Variety of Random Variables

NASA Technical Reports Server (NTRS)

Holland, Frederic A., Jr.

1997-01-01

Designing reliable structures requires an estimate of the maximum and minimum values (i.e., strength and load) that may be encountered in service. Yet designs based on very extreme values (to insure safety) can result in extra material usage and hence, uneconomic systems. In aerospace applications, severe over-design cannot be tolerated making it almost mandatory to design closer to the assumed limits of the design random variables. The issue then is predicting extreme values that are practical, i.e. neither too conservative or non-conservative. Obtaining design values by employing safety factors is well known to often result in overly conservative designs and. Safety factor values have historically been selected rather arbitrarily, often lacking a sound rational basis. To answer the question of how safe a design needs to be has lead design theorists to probabilistic and statistical methods. The so-called three-sigma approach is one such method and has been described as the first step in utilizing information about the data dispersion. However, this method is based on the assumption that the random variable is dispersed symmetrically about the mean and is essentially limited to normally distributed random variables. Use of this method can therefore result in unsafe or overly conservative design allowables if the common assumption of normality is incorrect.

Recoding aminoacyl-tRNA synthetases for synthetic biology by rational protein-RNA engineering.

PubMed

Hadd, Andrew; Perona, John J

2014-12-19

We have taken a rational approach to redesigning the amino acid binding and aminoacyl-tRNA pairing specificities of bacterial glutaminyl-tRNA synthetase. The four-stage engineering incorporates generalizable design principles and improves the pairing efficiency of noncognate glutamate with tRNA(Gln) by over 10(5)-fold compared to the wild-type enzyme. Better optimized designs of the protein-RNA complex include substantial reengineering of the globular core region of the tRNA, demonstrating a role for specific tRNA nucleotides in specifying the identity of the genetically encoded amino acid. Principles emerging from this engineering effort open new prospects for combining rational and genetic selection approaches to design novel aminoacyl-tRNA synthetases that ligate noncanonical amino acids onto tRNAs. This will facilitate reconstruction of the cellular translation apparatus for applications in synthetic biology.

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

PubMed

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.

Design of the sample cell in near-field surface-enhanced Raman scattering by finite difference time domain method

NASA Astrophysics Data System (ADS)

Li, Yaqin; Jian, Guoshu; Wu, Shifa

2006-11-01

The rational design of the sample cell may improve the sensitivity of surface-enhanced Raman scattering (SERS) detection in a high degree. Finite difference time domain (FDTD) simulations of the configuration of Ag film-Ag particles illuminated by plane wave and evanescent wave are performed to provide physical insight for design of the sample cell. Numerical solutions indicate that the sample cell can provide more "hot spots' and the massive field intensity enhancement occurs in these "hot spots'. More information on the nanometer character of the sample can be got because of gradient-field Raman (GFR) of evanescent wave.

STEEP STREAMS - Solid Transport Evaluation and Efficiency in Prevention: Sustainable Techniques of Rational Engineering and Advanced MethodS

NASA Astrophysics Data System (ADS)

Armanini, Aronne; Cardoso, Antonio H.; Di Baldassarre, Giuliano; Bellin, Alberto; Breinl, Korbinian; Canelas, Ricardo B.; Larcher, Michele; Majone, Bruno; Matos, Jorges; Meninno, Sabrina; Nucci, Elena; Rigon, Riccardo; Rosatti, Giorgio; Zardi, Dino

2017-04-01

The STEEP STREAMS (Solid Transport Evaluation and Efficiency in Prevention: Sustainable Techniques of Rational Engineering and Advanced MethodS) project consists of a collaboration among the Universities of Trento, Uppsala and Lisbon, who joined in a consortium within the ERANET Water JPI call WaterWorks2014. The aim of the project is to produce new rational criteria for the design of protection works against debris flows, a phenomenon consisting in hyper-concentrated flows of water and sediments, classified as catastrophic events typical of small mountainous basins (area <10 km2) and triggered by intense rainstorms. Such events are non-stationary phenomena that arise in a very short time, and their recurrence is rather difficult to determine. Compared to flash floods, they are more difficult to anticipate, mostly since they are triggered by convective precipitation events, posing a higher risk of damage and even loss of human lives. These extreme events occur almost annually across Europe, though the formal return period in an exposed site is much larger. Recently, an increase in intensity and frequency of small-scale storm events, leading to extreme solid transport in steep channels, are recognized as one of the effects of climate change. In this context, one of the key challenges of this project is the use of comparatively coarse RCM projections to the small catchments examined in STEEP STREAMS. Given these changes, conventional protection works and their design criteria may not suffice to provide adequate levels of protection to human life and urban settlements. These structures create a storage area upstream the alluvial fans and the settlements, thereby reducing the need of channelization in areas often constrained by urban regulations. To optimize the lamination, and in particular to reduce the peak of solid mass flux, it is necessary that the deposition basin is controlled by a slit check dam, capable of inducing a controlled sedimentation of the solid mas flux. In order to achieve that, reliable design tools are needed. Driftwood represents another important factor increasing the risk, as clogging induced by the vegetal material represents a major problem for the operational reliability of slit check dams. Current procedures in compiling hazardous maps do not account for such effects. The STEEPS STREAMS project aims at developing structural innovative solutions and design criteria reliable to mitigate the impacts of flash floods and debris flows especially in presence of intense woody material transport, typical of mountain catchments.

Series-nonuniform rational B-spline signal feedback: From chaos to any embedded periodic orbit or target point.

PubMed

Shao, Chenxi; Xue, Yong; Fang, Fang; Bai, Fangzhou; Yin, Peifeng; Wang, Binghong

2015-07-01

The self-controlling feedback control method requires an external periodic oscillator with special design, which is technically challenging. This paper proposes a chaos control method based on time series non-uniform rational B-splines (SNURBS for short) signal feedback. It first builds the chaos phase diagram or chaotic attractor with the sampled chaotic time series and any target orbit can then be explicitly chosen according to the actual demand. Second, we use the discrete timing sequence selected from the specific target orbit to build the corresponding external SNURBS chaos periodic signal, whose difference from the system current output is used as the feedback control signal. Finally, by properly adjusting the feedback weight, we can quickly lead the system to an expected status. We demonstrate both the effectiveness and efficiency of our method by applying it to two classic chaotic systems, i.e., the Van der Pol oscillator and the Lorenz chaotic system. Further, our experimental results show that compared with delayed feedback control, our method takes less time to obtain the target point or periodic orbit (from the starting point) and that its parameters can be fine-tuned more easily.

Series-nonuniform rational B-spline signal feedback: From chaos to any embedded periodic orbit or target point

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

Shao, Chenxi, E-mail: cxshao@ustc.edu.cn; Xue, Yong; Fang, Fang

2015-07-15

The self-controlling feedback control method requires an external periodic oscillator with special design, which is technically challenging. This paper proposes a chaos control method based on time series non-uniform rational B-splines (SNURBS for short) signal feedback. It first builds the chaos phase diagram or chaotic attractor with the sampled chaotic time series and any target orbit can then be explicitly chosen according to the actual demand. Second, we use the discrete timing sequence selected from the specific target orbit to build the corresponding external SNURBS chaos periodic signal, whose difference from the system current output is used as the feedbackmore » control signal. Finally, by properly adjusting the feedback weight, we can quickly lead the system to an expected status. We demonstrate both the effectiveness and efficiency of our method by applying it to two classic chaotic systems, i.e., the Van der Pol oscillator and the Lorenz chaotic system. Further, our experimental results show that compared with delayed feedback control, our method takes less time to obtain the target point or periodic orbit (from the starting point) and that its parameters can be fine-tuned more easily.« less

Protein Engineering Approaches in the Post-Genomic Era.

PubMed

Singh, Raushan K; Lee, Jung-Kul; Selvaraj, Chandrabose; Singh, Ranjitha; Li, Jinglin; Kim, Sang-Yong; Kalia, Vipin C

2018-01-01

Proteins are one of the most multifaceted macromolecules in living systems. Proteins have evolved to function under physiological conditions and, therefore, are not usually tolerant of harsh experimental and environmental conditions. The growing use of proteins in industrial processes as a greener alternative to chemical catalysts often demands constant innovation to improve their performance. Protein engineering aims to design new proteins or modify the sequence of a protein to create proteins with new or desirable functions. With the emergence of structural and functional genomics, protein engineering has been invigorated in the post-genomic era. The three-dimensional structures of proteins with known functions facilitate protein engineering approaches to design variants with desired properties. There are three major approaches of protein engineering research, namely, directed evolution, rational design, and de novo design. Rational design is an effective method of protein engineering when the threedimensional structure and mechanism of the protein is well known. In contrast, directed evolution does not require extensive information and a three-dimensional structure of the protein of interest. Instead, it involves random mutagenesis and selection to screen enzymes with desired properties. De novo design uses computational protein design algorithms to tailor synthetic proteins by using the three-dimensional structures of natural proteins and their folding rules. The present review highlights and summarizes recent protein engineering approaches, and their challenges and limitations in the post-genomic era. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A decade of vaccines: Integrating immunology and vaccinology for rational vaccine design.

PubMed

D'Argenio, David A; Wilson, Christopher B

2010-10-29

Vaccination stands as one of the most successful public health measures of the last century. New approaches will be needed, however, to develop highly effective vaccines to prevent tuberculosis, HIV-AIDS, and malaria and to eradicate polio. Current advances in immunology and technology have set the stage for rational vaccine design to begin a "Decade of Vaccines." Copyright © 2010 Elsevier Inc. All rights reserved.

Study on the methods of rational analysis about the area of the Planning of Sea Usage of Regional Construction

NASA Astrophysics Data System (ADS)

Ya-Juan, Li; Tian-Yu, Mao; Mingjing-Tian

2018-03-01

The Planning of Sea Usage of Regional Construction is a new area, and the rational analysis about the area of which is one of its difficulties. Based on “Urban land classification and land use planning and construction standards”, the land use control index method study the rationality of the sea usage area of the whole region, by accumulating for specific land use indicators for each land type within the planning area. This paper, takeing the project named “caofeidian integrated service area” for example, make a little study on the land use control index method used by the sea usage demonstration of the planning of sea usage of regional construction. The study will be good for improving the technical methods of rational analysis about the area of the planning of sea usage of regional construction.

Advanced Energy Storage Devices: Basic Principles, Analytical Methods, and Rational Materials Design

PubMed Central

Liu, Jilei; Wang, Jin; Xu, Chaohe; Li, Chunzhong; Lin, Jianyi

2017-01-01

Abstract Tremendous efforts have been dedicated into the development of high‐performance energy storage devices with nanoscale design and hybrid approaches. The boundary between the electrochemical capacitors and batteries becomes less distinctive. The same material may display capacitive or battery‐like behavior depending on the electrode design and the charge storage guest ions. Therefore, the underlying mechanisms and the electrochemical processes occurring upon charge storage may be confusing for researchers who are new to the field as well as some of the chemists and material scientists already in the field. This review provides fundamentals of the similarities and differences between electrochemical capacitors and batteries from kinetic and material point of view. Basic techniques and analysis methods to distinguish the capacitive and battery‐like behavior are discussed. Furthermore, guidelines for material selection, the state‐of‐the‐art materials, and the electrode design rules to advanced electrode are proposed. PMID:29375964

Advanced Energy Storage Devices: Basic Principles, Analytical Methods, and Rational Materials Design.

PubMed

Liu, Jilei; Wang, Jin; Xu, Chaohe; Jiang, Hao; Li, Chunzhong; Zhang, Lili; Lin, Jianyi; Shen, Ze Xiang

2018-01-01

Tremendous efforts have been dedicated into the development of high-performance energy storage devices with nanoscale design and hybrid approaches. The boundary between the electrochemical capacitors and batteries becomes less distinctive. The same material may display capacitive or battery-like behavior depending on the electrode design and the charge storage guest ions. Therefore, the underlying mechanisms and the electrochemical processes occurring upon charge storage may be confusing for researchers who are new to the field as well as some of the chemists and material scientists already in the field. This review provides fundamentals of the similarities and differences between electrochemical capacitors and batteries from kinetic and material point of view. Basic techniques and analysis methods to distinguish the capacitive and battery-like behavior are discussed. Furthermore, guidelines for material selection, the state-of-the-art materials, and the electrode design rules to advanced electrode are proposed.

The Cornell Kitchen: Housing and Design Research in Postwar America.

PubMed

Penner, Barbara

2018-01-01

The Cornell Kitchen (1950-55) was produced at Cornell University by a multidisciplinary team with expertise in home economics, engineering, architecture, and psychology. It promised to deliver rational design, functional principles, aesthetic appeal, and emotional satisfaction in one prefabricated, easy-to-install package. This article sets out the kitchen's history from its design to its field-testing phase to its impact on postwar kitchens. It argues that the kitchen represents an important effort to approach housing in a more scientific way; scientific methods were deployed to understand both the physical and socio-psychological problems of dwelling. The project also sought to introduce a specific model for leveraging housing research into the real world, partnering with industry to mass produce scientific designs. Social scientific methods were hence used to create not only more livable but also more saleable products in an effort to appeal to manufacturers and consumers alike.

Healthcare rationing: issues and implications.

PubMed

Cypher, D P

1997-01-01

What methods, if any, should be used to practice healthcare rationing? This article looks at healthcare rationing in the United States, identifies ethical issues associated with implementing healthcare rationing, and addresses legal implications. The author utilizes sources from published literature and her own experience. Society must recognize that it does not have the resources available to fulfill all healthcare needs of all its members. Resolution will bring conflict and compromise.

Function combined method for design innovation of children's bike

NASA Astrophysics Data System (ADS)

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.

Optical design of soft multifocal contact lens with uniform optical power in center-distance zone with optimized NURBS.

PubMed

Vu, Lien T; Chen, Chao-Chang A; Yu, Chia-Wei

2018-02-05

This study aims to develop a new optical design method of soft multifocal contact lens (CLs) to obtain uniform optical power in large center-distance zone with optimized Non-Uniform Rational B-spline (NURBS). For the anterior surface profiles of CLs, the NURBS design curves are optimized to match given optical power distributions. Then, the NURBS in the center-distance zones are fitted in the corresponding spherical/aspheric curves for both data points and their centers of curvature to achieve the uniform power. Four cases of soft CLs have been manufactured by casting in shell molds by injection molding and then measured to verify the design specifications. Results of power profiles of these CLs are concord with the given clinical requirements of uniform powers in larger center-distance zone. The developed optical design method has been verified for multifocal CLs design and can be further applied for production of soft multifocal CLs.

Monotonicity preserving splines using rational cubic Timmer interpolation

NASA Astrophysics Data System (ADS)

Zakaria, Wan Zafira Ezza Wan; Alimin, Nur Safiyah; Ali, Jamaludin Md

2017-08-01

In scientific application and Computer Aided Design (CAD), users usually need to generate a spline passing through a given set of data, which preserves certain shape properties of the data such as positivity, monotonicity or convexity. The required curve has to be a smooth shape-preserving interpolant. In this paper a rational cubic spline in Timmer representation is developed to generate interpolant that preserves monotonicity with visually pleasing curve. To control the shape of the interpolant three parameters are introduced. The shape parameters in the description of the rational cubic interpolant are subjected to monotonicity constrained. The necessary and sufficient conditions of the rational cubic interpolant are derived and visually the proposed rational cubic Timmer interpolant gives very pleasing results.

Characterizing Storm Event Dynamics of a Forested Watershed in the Lower Atlantic Coastal Plain, South Carolina USA

NASA Astrophysics Data System (ADS)

Latorre Torres, I. B.; Amatya, D. M.; Callahan, T. J.; Levine, N. S.

2007-12-01

Hydrology research in the Southeast U.S. has primarily focused on upland mountainous areas; however, much less is known about hydrological processes in Lower Coastal Plain (LCP) watersheds. Such watersheds are difficult to characterize due to shallow water table conditions, low topographic gradient, complex surface- subsurface water interaction, and lack of detailed soil information. Although opportunities to conduct long term monitoring in relatively undeveloped watersheds are often limited, stream flow and rainfall in the Turkey Creek watershed (third-order watershed, about 7200 ha in the Francis Marion National Forest near Charleston, SC) have been monitored since 1964. In this study, event runoff-rainfall ratios have been determined for 51 storm events using historical data from 1964-1973. One of our objectives was to characterize relationships between seasonal event rainfall and storm outflow in this watershed. To this end, observed storm event data were compared with values predicted by established hydrological methods such as the Soil Conservation Service runoff curve number (SCS-CN) and the rational method integrated within a Geographical Information System (GIS), to estimate total event runoff and peak discharge, respectively. Available 1:15000 scale aerial images were digitized to obtain land uses, which were used with the SCS soil hydrologic groups to obtain the runoff coefficients (C) for the rational method and the CN values for the SCS-CN method. These methods are being tested with historical storm event responses in the Turkey Creek watershed scale, and then will be used to predict event runoff in Quinby Creek, an ungauged third-order watershed (8700 ha) adjacent to Turkey Creek. Successful testing with refinement of parameters in the rational method and SCS-CN method, both designed for small urban and agricultural dominated watersheds, may allow widespread application of these methods for studying the event rainfall-runoff dynamics for similar watersheds in the Lower Coastal Plain of the Southeast U.S.

Elucidating Solvation Structures for Rational Design of Multivalent Electrolytes-A Review.

PubMed

Rajput, Nav Nidhi; Seguin, Trevor J; Wood, Brandon M; Qu, Xiaohui; Persson, Kristin A

2018-04-26

Fundamental molecular-level understanding of functional properties of liquid solutions provides an important basis for designing optimized electrolytes for numerous applications. In particular, exhaustive knowledge of solvation structure, stability, and transport properties is critical for developing stable electrolytes for fast-charging and high-energy-density next-generation energy storage systems. Accordingly, there is growing interest in the rational design of electrolytes for beyond lithium-ion systems by tuning the molecular-level interactions of solvate species present in the electrolytes. Here we present a review of the solvation structure of multivalent electrolytes and its impact on the electrochemical performance of these batteries. A direct correlation between solvate species present in the solution and macroscopic properties of electrolytes is sparse for multivalent electrolytes and contradictory results have been reported in the literature. This review aims to illustrate the current understanding, compare results, and highlight future needs and directions to enable the deep understanding needed for the rational design of improved multivalent electrolytes.

Professional practices and perception towards rational use of medicines according to WHO methodology in United Arab Emirates

PubMed Central

Abdul Rasool, Bazigha K.; Fahmy, Sahar A.; Abu-Gharbieh, Eman F.; Ali, Heyam S.

2009-01-01

Inappropriate prescribing reduces the quality of medical care and leads to a waste of resources. No study has been reported concerning rational drug use in United Arab Emirates, UAE, recently. Objectives assessing patterns of use and defining problems regarding the rational drug use.Setting baseline situational analysis study for practices in the health care system relevant to drug use. Method A descriptive pilot study, consisting of pharmacists, physicians and patients (100 of each of category) from four private hospitals, (12) medical clinics, (80) community pharmacies in addition to 150 prescriptions. A questionnaire of three sections was designed to include WHO indicators regarding patients, facility and prescribing patterns that are relevant to rational drug use was carried out in four emirates of the UAE in the period December 2008-Febreuary 2009. Results Consultation and dispensing times were 10 (SD=2.75) min and 68 (SD=9.7) seconds, respectively. Average no. of drugs per prescription was (2.9 + 0.97), % of prescriptions using generic name (7.35%), % of antibiotic containing prescriptions (31.1%), % of injection containing prescriptions (2.9%), adherence to Standard Treatment Protocols (46%), adherence to the essential drug list (64%), patient’s knowledge of correct dosage (55%), adequately labeled drugs (45%), patient’s information (65%). Conclusions Several areas of deficiency in rational drug use had been defined in the private sector through UAE that can be remedied through adopting several strategies such as adherence to national standard treatment guidelines and essential drug list based on treatments of choice, interaction between health care system and providing drugs information to consumers. PMID:25152796

Ethical principles and the rationing of health care: a qualitative study in general practice

PubMed Central

Berney, Lee; Kelly, Moira; Doyal, Len; Feder, Gene; Griffiths, Chris; Jones, Ian Rees

2005-01-01

Background Researching sensitive topics, such as the rationing of treatments and denial of care, raises a number of ethical and methodological problems. Aim To describe the methods and findings from a number of focus group discussions that examined how GPs apply ethical principles when allocating scarce resources. Design of study A small-scale qualitative study involving purposive sampling, semi-structured interviews and focus groups. Setting Twenty-four GPs from two contrasting areas of London: one relatively affluent and one relatively deprived. Method Initial interviews asked GPs to identify key resource allocation issues. The interviews were transcribed and themes were identified. A number of case studies, each illustrative of an ethical issue related to rationing, were written up in the form of vignettes. In focus group discussions, GPs were given a number of these vignettes to debate. Results With respect to the ethical basis for decision making, the findings from this part of the study emphasised the role of social and psychological factors, the influence of the quality of the relationship between GPs and patients and confusion among GPs about their role in decision making. Conclusion The use of vignettes developed from prior interviews with GPs creates a non-threatening environment to discuss sensitive or controversial issues. The acceptance by GPs of general moral principles does not entail clarity of coherence of the application of these principles in practice. PMID:16105371

Design of Mobile Augmented Reality in Health Care Education: A Theory-Driven Framework

PubMed Central

Lilienthal, Anneliese; Shluzas, Lauren Aquino; Masiello, Italo; Zary, Nabil

2015-01-01

Background Augmented reality (AR) is increasingly used across a range of subject areas in health care education as health care settings partner to bridge the gap between knowledge and practice. As the first contact with patients, general practitioners (GPs) are important in the battle against a global health threat, the spread of antibiotic resistance. AR has potential as a practical tool for GPs to combine learning and practice in the rational use of antibiotics. Objective This paper was driven by learning theory to develop a mobile augmented reality education (MARE) design framework. The primary goal of the framework is to guide the development of AR educational apps. This study focuses on (1) identifying suitable learning theories for guiding the design of AR education apps, (2) integrating learning outcomes and learning theories to support health care education through AR, and (3) applying the design framework in the context of improving GPs’ rational use of antibiotics. Methods The design framework was first constructed with the conceptual framework analysis method. Data were collected from multidisciplinary publications and reference materials and were analyzed with directed content analysis to identify key concepts and their relationships. Then the design framework was applied to a health care educational challenge. Results The proposed MARE framework consists of three hierarchical layers: the foundation, function, and outcome layers. Three learning theories—situated, experiential, and transformative learning—provide foundational support based on differing views of the relationships among learning, practice, and the environment. The function layer depends upon the learners’ personal paradigms and indicates how health care learning could be achieved with MARE. The outcome layer analyzes different learning abilities, from knowledge to the practice level, to clarify learning objectives and expectations and to avoid teaching pitched at the wrong level. Suggestions for learning activities and the requirements of the learning environment form the foundation for AR to fill the gap between learning outcomes and medical learners’ personal paradigms. With the design framework, the expected rational use of antibiotics by GPs is described and is easy to execute and evaluate. The comparison of specific expected abilities with the GP personal paradigm helps solidify the GP practical learning objectives and helps design the learning environment and activities. The learning environment and activities were supported by learning theories. Conclusions This paper describes a framework for guiding the design, development, and application of mobile AR for medical education in the health care setting. The framework is theory driven with an understanding of the characteristics of AR and specific medical disciplines toward helping medical education improve professional development from knowledge to practice. Future research will use the framework as a guide for developing AR apps in practice to validate and improve the design framework. PMID:27731839

Tunable emission in lanthanide coordination polymer gels based on a rationally designed blue emissive gelator.

PubMed

Sutar, Papri; Suresh, Venkata M; Maji, Tapas Kumar

2015-06-18

Rational design and synthesis of a new low molecular weight gelator (LMWG) having 9,10-diphenylanthracene core and terminal terpyridine is reported. Tb(III) and Eu(III) ion coordination to a LMWG results in green and pink emissive coordination polymer gels, respectively, with coiled nanofiber morphology. Further, control over stoichiometry of LMWG:Tb(III):Eu(III) leads to yellow and white light emitting bimetallic gels.

Dual kinase-bromodomain inhibitors for rationally designed polypharmacology

PubMed Central

Ciceri, Pietro; Müller, Susanne; O’Mahony, Alison; Fedorov, Oleg; Filippakopoulos, Panagis; Hunt, Jeremy P.; Lasater, Elisabeth A.; Pallares, Gabriel; Picaud, Sarah; Wells, Christopher; Martin, Sarah; Wodicka, Lisa M.; Shah, Neil P.; Treiber, Daniel K.; Knapp, Stefan

2014-01-01

Concomitant inhibition of multiple cancer-driving kinases is an established strategy to improve the durability of clinical responses to targeted therapies. The difficulty of discovering kinase inhibitors with an appropriate multi-target profile has, however, necessitated the application of combination therapies, which can pose significant clinical development challenges. Epigenetic reader domains of the bromodomain family have recently emerged as novel targets for cancer therapy. Here we report that several clinical kinase inhibitors also inhibit bromodomains with therapeutically relevant potencies and are best classified as dual kinase/bromodomain inhibitors. Nanomolar activity on BRD4 by BI-2536 and TG-101348, clinical PLK1 and JAK2/FLT3 kinase inhibitors, respectively, is particularly noteworthy as these combinations of activities on independent oncogenic pathways exemplify a novel strategy for rational single agent polypharmacological targeting. Furthermore, structure-activity relationships and co-crystal structures identify design features that enable a general platform for the rational design of dual kinase/bromodomain inhibitors. PMID:24584101

TRO-2D - A code for rational transonic aerodynamic optimization

NASA Technical Reports Server (NTRS)

Davis, W. H., Jr.

1985-01-01

Features and sample applications of the transonic rational optimization (TRO-2D) code are outlined. TRO-2D includes the airfoil analysis code FLO-36, the CONMIN optimization code and a rational approach to defining aero-function shapes for geometry modification. The program is part of an effort to develop an aerodynamically smart optimizer that will simplify and shorten the design process. The user has a selection of drag minimization and associated minimum lift, moment, and the pressure distribution, a choice among 14 resident aero-function shapes, and options on aerodynamic and geometric constraints. Design variables such as the angle of attack, leading edge radius and camber, shock strength and movement, supersonic pressure plateau control, etc., are discussed. The results of calculations of a reduced leading edge camber transonic airfoil and an airfoil with a natural laminar flow are provided, showing that only four design variables need be specified to obtain satisfactory results.

Rational-Emotive Therapy versus Systematic Desensitization: A Comment on Moleski and Tosi.

ERIC Educational Resources Information Center

Atkinson, Leslie

1983-01-01

Questioned the statistical analyses of the Moleski and Tosi investigation of rational-emotive therapy versus systematic desensitization. Suggested means for lowering the error rate through a more efficient experimental design. Recommended a reanalysis of the original data. (LLL)

Lower bound buckling loads for design of laminate composite cylinders

NASA Astrophysics Data System (ADS)

Croll, James G. A.; Wang, Hongtao

2017-01-01

Over a period of more than 45 years, an extensive research program has allowed a series of very simple propositions, relating to the safe design of shells experiencing imperfection sensitive buckling, to be recast in the form of a series of lemmas. These are briefly summarized and their practical use is illustrated in relation to the prediction of safe lower bounds to the imperfection sensitive buckling of axially loaded, fiber reinforced polymeric, laminated cylinders. With a fundamental aspect of the approach, sometimes referred to as the reduced stiffness method, being the delineation of the various shell membrane and bending stiffness (or perhaps more appropriately energy) components contributing to the buckling resistance, the method will be shown to also provide a powerful way of making rational design decisions to optimize the use of fiber reinforcement.

The application of powerful promoters to enhance gene expression in industrial microorganisms.

PubMed

Zhou, Shenghu; Du, Guocheng; Kang, Zhen; Li, Jianghua; Chen, Jian; Li, Huazhong; Zhou, Jingwen

2017-02-01

Production of useful chemicals by industrial microorganisms has been attracting more and more attention. Microorganisms screened from their natural environment usually suffer from low productivity, low stress resistance, and accumulation of by-products. In order to overcome these disadvantages, rational engineering of microorganisms to achieve specific industrial goals has become routine. Rapid development of metabolic engineering and synthetic biology strategies provide novel methods to improve the performance of industrial microorganisms. Rational regulation of gene expression by specific promoters is essential to engineer industrial microorganisms for high-efficiency production of target chemicals. Identification, modification, and application of suitable promoters could provide powerful switches at the transcriptional level for fine-tuning of a single gene or a group of genes, which are essential for the reconstruction of pathways. In this review, the characteristics of promoters from eukaryotic, prokaryotic, and archaea microorganisms are briefly introduced. Identification of promoters based on both traditional biochemical and systems biology routes are summarized. Besides rational modification, de novo design of promoters to achieve gradient, dynamic, and logic gate regulation are also introduced. Furthermore, flexible application of static and dynamic promoters for the rational engineering of industrial microorganisms is highlighted. From the perspective of powerful promoters in industrial microorganisms, this review will provide an extensive description of how to regulate gene expression in industrial microorganisms to achieve more useful goals.

Factors that impact on emergency nurses' ethical decision-making ability.

PubMed

Alba, Barbara

2016-11-10

Reliance on moral principles and professional codes has given nurses direction for ethical decision-making. However, rational models do not capture the emotion and reality of human choice. Intuitive response must be considered. Supporting intuition as an important ethical decision-making tool for nurses, the aim of this study was to determine relationships between intuition, years of worked nursing experience, and perceived ethical decision-making ability. A secondary aim explored the relationships between rational thought to years of worked nursing experience and perceived ethical decision-making ability. A non-experimental, correlational research design was used. The Rational Experiential Inventory measured intuition and rational thought. The Clinical Decision Making in Nursing Scale measured perceived ethical decision-making ability. Pearson's r was the statistical method used to analyze three primary and two secondary research questions. A sample of 182 emergency nurses was recruited electronically through the Emergency Nurses Association. Participants were self-selected. Approval to conduct this study was obtained by the Adelphi University Institutional Review Board. A relationship between intuition and perceived ethical decision-making ability (r = .252, p = .001) was a significant finding in this study. This study is one of the first of this nature to make a connection between intuition and nurses' ethical decision-making ability. This investigation contributes to a broader understanding of the different thought processes used by emergency nurses to make ethical decisions. © The Author(s) 2016.

Rational design of therapeutic mAbs against aggregation through protein engineering and incorporation of glycosylation motifs applied to bevacizumab

PubMed Central

Courtois, Fabienne; Agrawal, Neeraj J; Lauer, Timothy M; Trout, Bernhardt L

2016-01-01

The aggregation of biotherapeutics is a major hindrance to the development of successful drug candidates; however, the propensity to aggregate is often identified too late in the development phase to permit modification to the protein's sequence. Incorporating rational design for the stability of proteins in early discovery has numerous benefits. We engineered out aggregation-prone regions on the Fab domain of a therapeutic monoclonal antibody, bevacizumab, to rationally design a biobetter drug candidate. With the purpose of stabilizing bevacizumab with respect to aggregation, 2 strategies were undertaken: single point mutations of aggregation-prone residues and engineering a glycosylation site near aggregation-prone residues to mask these residues with a carbohydrate moiety. Both of these approaches lead to comparable decreases in aggregation, with an up to 4-fold reduction in monomer loss. These single mutations and the new glycosylation pattern of the Fab domain do not modify binding to the target. Biobetters with increased stability against aggregation can therefore be generated in a rational manner, by either removing or masking the aggregation-prone region or crowding out protein-protein interactions. PMID:26514585

Task analysis exemplified: the process of resolving unfinished business.

PubMed

Greenberg, L S; Foerster, F S

1996-06-01

The steps of a task-analytic research program designed to identify the in-session performances involved in resolving lingering bad feelings toward a significant other are described. A rational-empirical methodology of repeatedly cycling between rational conjecture and empirical observations is demonstrated as a method of developing an intervention manual and the components of client processes of resolution. A refined model of the change process developed by these procedures is validated by comparing 11 successful and 11 unsuccessful performances. Four performance components-intense expression of feeling, expression of need, shift in representation of other, and self-validation or understanding of the other-were found to discriminate between resolution and nonresolution performances. These components were measured on 4 process measures: the Structural Analysis of Social Behavior, the Experiencing Scale, the Client's Emotional Arousal Scale, and a need scale.

Tuning calcite morphology and growth acceleration by a rational design of highly stable protein-mimetics

NASA Astrophysics Data System (ADS)

Chen, Chun-Long; Qi, Jiahui; Tao, Jinhui; Zuckermann, Ronald N.; Deyoreo, James J.

2014-09-01

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.

Systems Vaccinology: Enabling rational vaccine design with systems biological approaches

PubMed Central

Hagan, Thomas; Nakaya, Helder I.; Subramaniam, Shankar; Pulendran, Bali

2015-01-01

Vaccines have drastically reduced the mortality and morbidity of many diseases. However, vaccines have historically been developed empirically, and recent development of vaccines against current pandemics such as HIV and malaria has been met with difficulty. The advent of high-throughput technologies, coupled with systems biological methods of data analysis, has enabled researchers to interrogate the entire complement of a variety of molecular components within cells, and characterize the myriad interactions among them in order to model and understand the behavior of the system as a whole. In the context of vaccinology, these tools permit exploration of the molecular mechanisms by which vaccines induce protective immune responses. Here we review the recent advances, challenges, and potential of systems biological approaches in vaccinology. If the challenges facing this developing field can be overcome, systems vaccinology promises to empower the identification of early predictive signatures of vaccine response, as well as novel and robust correlates of protection from infection. Such discoveries, along with the improved understanding of immune responses to vaccination they impart, will play an instrumental role in development of the next generation of rationally designed vaccines. PMID:25858860

Tuning calcite morphology and growth acceleration by a rational design of highly stable protein-mimetics

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

Chen, Chunlong; Qi, Jiahui; Tao, Jinhui

2014-09-05

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 interactions (EI) and hydrophobic interactions (HI), with HI playing the dominant role. While either strong EI or HI inhibit growth and suppress (104) face expression, correlations between peptoid-crystal binding energiesmore » and observed changes in calcite growth indicate moderate EI allow peptoids to weakly adsorb while moderate HI cause disruption of surface-adsorbed water layers, leading to growth acceleration with retained expression of (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.« less

Tuning calcite morphology and growth acceleration by a rational design of highly stable protein-mimetics

PubMed Central

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

Options as information: rational reversals of evaluation and preference.

PubMed

Sher, Shlomi; McKenzie, Craig R M

2014-06-01

This article develops a rational analysis of an important class of apparent preference reversals-joint-separate reversals traditionally explained by the evaluability hypothesis. The "options-as-information" model considers a hypothetical rational actor with limited knowledge about the market distribution of a stimulus attribute. The actor's evaluations are formed via a 2-stage process-an inferential stage in which beliefs are updated on the basis of the sample of options received, followed by an assessment stage in which options are evaluated in light of these updated beliefs. This process generates joint-separate reversals in standard experimental designs. The normative model explains why the evaluability hypothesis works when it does, identifies boundary conditions for the hypothesis, and clarifies some common misconceptions about these effects. In particular, it implies that joint-separate reversals are not irrational; in fact, they are not preference reversals. However, in expanded designs where more than 2 options are jointly evaluated, the model predicts that genuine (and rational) preference reversals will sometimes emerge. Results of 3 experiments suggest an excellent fit between the rational actor model and the judgments of human actors in joint-separate experiments. PsycINFO Database Record (c) 2014 APA, all rights reserved.

A Method for Computing Leading-Edge Loads

NASA Technical Reports Server (NTRS)

Rhode, Richard V; Pearson, Henry A

1933-01-01

In this report a formula is developed that enables the determination of the proper design load for the portion of the wing forward of the front spar. The formula is inherently rational in concept, as it takes into account the most important variables that affect the leading-edge load, although theoretical rigor has been sacrificed for simplicity and ease of application. Some empirical corrections, based on pressure distribution measurements on the PW-9 and M-3 airplanes have been introduced to provide properly for biplanes. Results from the formula check experimental values in a variety of cases with good accuracy in the critical loading conditions. The use of the method for design purposes is therefore felt to be justified and is recommended.

The Development of CK2 Inhibitors: From Traditional Pharmacology to in Silico Rational Drug Design

PubMed Central

Cozza, Giorgio

2017-01-01

Casein kinase II (CK2) is an ubiquitous and pleiotropic serine/threonine protein kinase able to phosphorylate hundreds of substrates. Being implicated in several human diseases, from neurodegeneration to cancer, the biological roles of CK2 have been intensively studied. Upregulation of CK2 has been shown to be critical to tumor progression, making this kinase an attractive target for cancer therapy. Several CK2 inhibitors have been developed so far, the first being discovered by “trial and error testing”. In the last decade, the development of in silico rational drug design has prompted the discovery, de novo design and optimization of several CK2 inhibitors, active in the low nanomolar range. The screening of big chemical libraries and the optimization of hit compounds by Structure Based Drug Design (SBDD) provide telling examples of a fruitful application of rational drug design to the development of CK2 inhibitors. Ligand Based Drug Design (LBDD) models have been also applied to CK2 drug discovery, however they were mainly focused on methodology improvements rather than being critical for de novo design and optimization. This manuscript provides detailed description of in silico methodologies whose applications to the design and development of CK2 inhibitors proved successful and promising. PMID:28230762

Rapid communication: Computational simulation and analysis of a candidate for the design of a novel silk-based biopolymer.

PubMed

Golas, Ewa I; Czaplewski, Cezary

2014-09-01

This work theoretically investigates the mechanical properties of a novel silk-derived biopolymer as polymerized in silico from sericin and elastin-like monomers. Molecular Dynamics simulations and Steered Molecular Dynamics were the principal computational methods used, the latter of which applies an external force onto the system and thereby enables an observation of its response to stress. The models explored herein are single-molecule approximations, and primarily serve as tools in a rational design process for the preliminary assessment of properties in a new material candidate. © 2014 Wiley Periodicals, Inc.

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

PubMed

Li, Minyong; Xia, Lin

2007-11-01

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

Nutrition for Health and Performance, 2000: Nutritional Guidance for Military Operations in Temperate and Extreme Environments.

DTIC Science & Technology

1999-12-01

processed , high-salt foods (read food labels). • If You Drink Alcoholic Beverages, Do So in Moderation - Alcoholic beverages supply calories but...military. Rations are made from "real foods" (commercially grown and processed ). Commercial brand name foods and military ration items are often...designed to simplify and streamline the process of providing group meals in the field by integrating components of A-Rations, and Heat & Serve (H & S

An n -material thresholding method for improving integerness of solutions in topology optimization

DOE PAGES

Watts, Seth; Tortorelli, Daniel A.

2016-04-10

It is common in solving topology optimization problems to replace an integer-valued characteristic function design field with the material volume fraction field, a real-valued approximation of the design field that permits "fictitious" mixtures of materials during intermediate iterations in the optimization process. This is reasonable so long as one can interpolate properties for such materials and so long as the final design is integer valued. For this purpose, we present a method for smoothly thresholding the volume fractions of an arbitrary number of material phases which specify the design. This method is trivial for two-material design problems, for example, themore » canonical topology design problem of specifying the presence or absence of a single material within a domain, but it becomes more complex when three or more materials are used, as often occurs in material design problems. We take advantage of the similarity in properties between the volume fractions and the barycentric coordinates on a simplex to derive a thresholding, method which is applicable to an arbitrary number of materials. As we show in a sensitivity analysis, this method has smooth derivatives, allowing it to be used in gradient-based optimization algorithms. Finally, we present results, which show synergistic effects when used with Solid Isotropic Material with Penalty and Rational Approximation of Material Properties material interpolation functions, popular methods of ensuring integerness of solutions.« less

A rational interpolation method to compute frequency response

NASA Technical Reports Server (NTRS)

Kenney, Charles; Stubberud, Stephen; Laub, Alan J.

1993-01-01

A rational interpolation method for approximating a frequency response is presented. The method is based on a product formulation of finite differences, thereby avoiding the numerical problems incurred by near-equal-valued subtraction. Also, resonant pole and zero cancellation schemes are developed that increase the accuracy and efficiency of the interpolation method. Selection techniques of interpolation points are also discussed.

Antigenicity and Immunogenicity in HIV-1 Antibody-Based Vaccine Design

PubMed Central

Kong, Leopold; Sattentau, Quentin J

2012-01-01

Neutralizing antibodies can protect from infection by immunodeficiency viruses. However, the induction by active vaccination of antibodies that can potently neutralize a broad range of circulating virus strains is a goal not yet achieved, despite more than 2 decades of research. Here we review progress made in the field, from early empirical studies to today’s rational structure-based vaccine antigen design. We discuss the existence of broadly neutralizing antibodies, their implications for epitope discovery and recent progress made in antigen design. Finally, we consider the relationship between antigenicity and immunogenicity for B cell recognition and antibody production, a major hurdle for rational vaccine design to overcome. PMID:23227445

Peptide-Directed PdAu Nanoscale Surface Segregation: Toward Controlled Bimetallic Architecture for Catalytic Materials

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

Bedford, Nicholas M.; Showalter, Allison R.; Woehl, Taylor J.

Bimetallic nanoparticles are of immense scientific and technological interest given the synergistic properties observed when mixing two different metallic species at the nanoscale. This is particularly prevalent in catalysis, where bimetallic nanoparticles often exhibit improved catalytic activity and durability over their monometallic counterparts. Yet despite intense research efforts, little is understood regarding how to optimize bimetallic surface composition and structure synthetically using rational design principles. Recently, it has been demonstrated that peptide-enabled routes for nanoparticle synthesis result in materials with sequence-dependent catalytic properties, providing an opportunity for rational design through sequence manipulation. In this study, bimetallic PdAu nanoparticles are synthesizedmore » with a small set of peptides containing known Pd and Au binding motifs. The resulting nanoparticles were extensively characterized using high-resolution scanning transmission electron microscopy, X-ray absorption spectroscopy and high-energy X-ray diffraction coupled to atomic pair distribution function analysis. Structural information obtained from synchrotron radiation methods were then used to generate model nanoparticle configurations using reverse Monte Carlo simulations, which illustrate sequence-dependence in both surface structure and surface composition. Replica exchange solute tempering molecular dynamic simulations were also used to predict the modes of peptide binding on monometallic surfaces, indicating that different sequences bind to the metal interfaces via different mechanisms. As a testbed reaction, electrocatalytic methanol oxidation experiments were performed, wherein differences in catalytic activity are clearly observed in materials with identical bimetallic composition. Finally, taken together, this study indicates that peptides could be used to arrive at bimetallic surfaces with enhanced catalytic properties, which could be leveraged for rational bimetallic nanoparticle design using peptide-enabled approaches.« less

Peptide-Directed PdAu Nanoscale Surface Segregation: Toward Controlled Bimetallic Architecture for Catalytic Materials

DOE PAGES

Bedford, Nicholas M.; Showalter, Allison R.; Woehl, Taylor J.; ...

2016-09-01

Bimetallic nanoparticles are of immense scientific and technological interest given the synergistic properties observed when mixing two different metallic species at the nanoscale. This is particularly prevalent in catalysis, where bimetallic nanoparticles often exhibit improved catalytic activity and durability over their monometallic counterparts. Yet despite intense research efforts, little is understood regarding how to optimize bimetallic surface composition and structure synthetically using rational design principles. Recently, it has been demonstrated that peptide-enabled routes for nanoparticle synthesis result in materials with sequence-dependent catalytic properties, providing an opportunity for rational design through sequence manipulation. In this study, bimetallic PdAu nanoparticles are synthesizedmore » with a small set of peptides containing known Pd and Au binding motifs. The resulting nanoparticles were extensively characterized using high-resolution scanning transmission electron microscopy, X-ray absorption spectroscopy and high-energy X-ray diffraction coupled to atomic pair distribution function analysis. Structural information obtained from synchrotron radiation methods were then used to generate model nanoparticle configurations using reverse Monte Carlo simulations, which illustrate sequence-dependence in both surface structure and surface composition. Replica exchange solute tempering molecular dynamic simulations were also used to predict the modes of peptide binding on monometallic surfaces, indicating that different sequences bind to the metal interfaces via different mechanisms. As a testbed reaction, electrocatalytic methanol oxidation experiments were performed, wherein differences in catalytic activity are clearly observed in materials with identical bimetallic composition. Finally, taken together, this study indicates that peptides could be used to arrive at bimetallic surfaces with enhanced catalytic properties, which could be leveraged for rational bimetallic nanoparticle design using peptide-enabled approaches.« less

The use of rational functions in numerical quadrature

NASA Astrophysics Data System (ADS)

Gautschi, Walter

2001-08-01

Quadrature problems involving functions that have poles outside the interval of integration can profitably be solved by methods that are exact not only for polynomials of appropriate degree, but also for rational functions having the same (or the most important) poles as the function to be integrated. Constructive and computational tools for accomplishing this are described and illustrated in a number of quadrature contexts. The superiority of such rational/polynomial methods is shown by an analysis of the remainder term and documented by numerical examples.

Barcode extension for analysis and reconstruction of structures

NASA Astrophysics Data System (ADS)

Myhrvold, Cameron; Baym, Michael; Hanikel, Nikita; Ong, Luvena L.; Gootenberg, Jonathan S.; Yin, Peng

2017-03-01

Collections of DNA sequences can be rationally designed to self-assemble into predictable three-dimensional structures. The geometric and functional diversity of DNA nanostructures created to date has been enhanced by improvements in DNA synthesis and computational design. However, existing methods for structure characterization typically image the final product or laboriously determine the presence of individual, labelled strands using gel electrophoresis. Here we introduce a new method of structure characterization that uses barcode extension and next-generation DNA sequencing to quantitatively measure the incorporation of every strand into a DNA nanostructure. By quantifying the relative abundances of distinct DNA species in product and monomer bands, we can study the influence of geometry and sequence on assembly. We have tested our method using 2D and 3D DNA brick and DNA origami structures. Our method is general and should be extensible to a wide variety of DNA nanostructures.

Barcode extension for analysis and reconstruction of structures.

PubMed

Myhrvold, Cameron; Baym, Michael; Hanikel, Nikita; Ong, Luvena L; Gootenberg, Jonathan S; Yin, Peng

2017-03-13

Collections of DNA sequences can be rationally designed to self-assemble into predictable three-dimensional structures. The geometric and functional diversity of DNA nanostructures created to date has been enhanced by improvements in DNA synthesis and computational design. However, existing methods for structure characterization typically image the final product or laboriously determine the presence of individual, labelled strands using gel electrophoresis. Here we introduce a new method of structure characterization that uses barcode extension and next-generation DNA sequencing to quantitatively measure the incorporation of every strand into a DNA nanostructure. By quantifying the relative abundances of distinct DNA species in product and monomer bands, we can study the influence of geometry and sequence on assembly. We have tested our method using 2D and 3D DNA brick and DNA origami structures. Our method is general and should be extensible to a wide variety of DNA nanostructures.

Barcode extension for analysis and reconstruction of structures

PubMed Central

Myhrvold, Cameron; Baym, Michael; Hanikel, Nikita; Ong, Luvena L; Gootenberg, Jonathan S; Yin, Peng

2017-01-01

Collections of DNA sequences can be rationally designed to self-assemble into predictable three-dimensional structures. The geometric and functional diversity of DNA nanostructures created to date has been enhanced by improvements in DNA synthesis and computational design. However, existing methods for structure characterization typically image the final product or laboriously determine the presence of individual, labelled strands using gel electrophoresis. Here we introduce a new method of structure characterization that uses barcode extension and next-generation DNA sequencing to quantitatively measure the incorporation of every strand into a DNA nanostructure. By quantifying the relative abundances of distinct DNA species in product and monomer bands, we can study the influence of geometry and sequence on assembly. We have tested our method using 2D and 3D DNA brick and DNA origami structures. Our method is general and should be extensible to a wide variety of DNA nanostructures. PMID:28287117

Specification for Visual Requirements of Work-Centered Software Systems

DTIC Science & Technology

2006-10-01

no person shall be subject to any penity for fallng to comply wih a collection of N ilo ration it does not display a currenty valid OMB control...work- aiding systems. Based on the design concept for a work- centered support system (WCSS), these software systems support user tasks and goals...through both direct and indirect aiding methods within the interface client. In order to ensure the coherent development and delivery of work- centered

Hypnosis and Rational-Emotive Therapy as Used in Teaching Improved Auto Suggestion.

ERIC Educational Resources Information Center

DeRoos, Yosikazu Spencer; Johnson, David Pittman

1983-01-01

Detailes a method incorporating hypnosis and Rational-Emotive Therapy (RET) into a procedure termed Rational-Emotive Hypnosis. Indicates several areas in which clients often have difficulty engaging successfully in RET, and offers hypnotic techniques to overcome such problems. Both direct and indirect hypnotic procedures are examined. (JAC)

Computer Aided Enzyme Design and Catalytic Concepts

PubMed Central

Frushicheva, Maria P.; Mills, Matthew J. L.; Schopf, Patrick; Singh, Manoj K.; Warshel, Arieh

2014-01-01

Gaining a deeper understanding of enzyme catalysis is of great practical and fundamental importance. Over the years it has become clear that despite advances made in experimental mutational studies, a quantitative understanding of enzyme catalysis will not be possible without the use of computer modeling approaches. While we believe that electrostatic preorganization is by far the most important catalytic factor, convincing the wider scientific community of this may require the demonstration of effective rational enzyme design. Here we make the point that the main current advances in enzyme design are basically advances in directed evolution and that computer aided enzyme design must involve approaches that can reproduce catalysis in well-defined test cases. Such an approach is provided by the empirical valence bond method. PMID:24814389

Enhancing the role of veterinary vaccines reducing zoonotic diseases of humans: Linking systems biology with vaccine development

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

Adams, Leslie G.; Khare, Sangeeta; Lawhon, Sara D.

The aim of research on infectious diseases is their prevention, and brucellosis and salmonellosis as such are classic examples of worldwide zoonoses for application of a systems biology approach for enhanced rational vaccine development. When used optimally, vaccines prevent disease manifestations, reduce transmission of disease, decrease the need for pharmaceutical intervention, and improve the health and welfare of animals, as well as indirectly protecting against zoonotic diseases of people. Advances in the last decade or so using comprehensive systems biology approaches linking genomics, proteomics, bioinformatics, and biotechnology with immunology, pathogenesis and vaccine formulation and delivery are expected to enable enhancedmore » approaches to vaccine development. The goal of this paper is to evaluate the role of computational systems biology analysis of host:pathogen interactions (the interactome) as a tool for enhanced rational design of vaccines. Systems biology is bringing a new, more robust approach to veterinary vaccine design based upon a deeper understanding of the host pathogen interactions and its impact on the host's molecular network of the immune system. A computational systems biology method was utilized to create interactome models of the host responses to Brucella melitensis (BMEL), Mycobacterium avium paratuberculosis (MAP), Salmonella enterica Typhimurium (STM), and a Salmonella mutant (isogenic *sipA, sopABDE2) and linked to the basis for rational development of vaccines for brucellosis and salmonellosis as reviewed by Adams et al. and Ficht et al. [1,2]. A bovine ligated ileal loop biological model was established to capture the host gene expression response at multiple time points post infection. New methods based on Dynamic Bayesian Network (DBN) machine learning were employed to conduct a comparative pathogenicity analysis of 219 signaling and metabolic pathways and 1620 gene ontology (GO) categories that defined the host's biosignatures to each infectious condition. Through this DBN computational approach, the method identified significantly perturbed pathways and GO category groups of genes that define the pathogenicity signatures of the infectious agent. Our preliminary results provide deeper understanding of the overall complexity of host innate immune response as well as the identification of host gene perturbations that defines a unique host temporal biosignature response to each pathogen. The application of advanced computational methods for developing interactome models based on DBNs has proven to be instrumental in elucidating novel host responses and improved functional biological insight into the host defensive mechanisms. Evaluating the unique differences in pathway and GO perturbations across pathogen conditions allowed the identification of plausible host pathogen interaction mechanisms. Accordingly, a systems biology approach to study molecular pathway gene expression profiles of host cellular responses to microbial pathogens holds great promise as a methodology to identify, model and predict the overall dynamics of the host pathogen interactome. Thus, we propose that such an approach has immediate application to the rational design of brucellosis and salmonellosis vaccines.« less

Enhancing the role of veterinary vaccines reducing zoonotic diseases of humans: linking systems biology with vaccine development.

PubMed

Adams, L Garry; Khare, Sangeeta; Lawhon, Sara D; Rossetti, Carlos A; Lewin, Harris A; Lipton, Mary S; Turse, Joshua E; Wylie, Dennis C; Bai, Yu; Drake, Kenneth L

2011-09-22

The aim of research on infectious diseases is their prevention, and brucellosis and salmonellosis as such are classic examples of worldwide zoonoses for application of a systems biology approach for enhanced rational vaccine development. When used optimally, vaccines prevent disease manifestations, reduce transmission of disease, decrease the need for pharmaceutical intervention, and improve the health and welfare of animals, as well as indirectly protecting against zoonotic diseases of people. Advances in the last decade or so using comprehensive systems biology approaches linking genomics, proteomics, bioinformatics, and biotechnology with immunology, pathogenesis and vaccine formulation and delivery are expected to enable enhanced approaches to vaccine development. The goal of this paper is to evaluate the role of computational systems biology analysis of host:pathogen interactions (the interactome) as a tool for enhanced rational design of vaccines. Systems biology is bringing a new, more robust approach to veterinary vaccine design based upon a deeper understanding of the host-pathogen interactions and its impact on the host's molecular network of the immune system. A computational systems biology method was utilized to create interactome models of the host responses to Brucella melitensis (BMEL), Mycobacterium avium paratuberculosis (MAP), Salmonella enterica Typhimurium (STM), and a Salmonella mutant (isogenic ΔsipA, sopABDE2) and linked to the basis for rational development of vaccines for brucellosis and salmonellosis as reviewed by Adams et al. and Ficht et al. [1,2]. A bovine ligated ileal loop biological model was established to capture the host gene expression response at multiple time points post infection. New methods based on Dynamic Bayesian Network (DBN) machine learning were employed to conduct a comparative pathogenicity analysis of 219 signaling and metabolic pathways and 1620 gene ontology (GO) categories that defined the host's biosignatures to each infectious condition. Through this DBN computational approach, the method identified significantly perturbed pathways and GO category groups of genes that define the pathogenicity signatures of the infectious agent. Our preliminary results provide deeper understanding of the overall complexity of host innate immune response as well as the identification of host gene perturbations that defines a unique host temporal biosignature response to each pathogen. The application of advanced computational methods for developing interactome models based on DBNs has proven to be instrumental in elucidating novel host responses and improved functional biological insight into the host defensive mechanisms. Evaluating the unique differences in pathway and GO perturbations across pathogen conditions allowed the identification of plausible host-pathogen interaction mechanisms. Accordingly, a systems biology approach to study molecular pathway gene expression profiles of host cellular responses to microbial pathogens holds great promise as a methodology to identify, model and predict the overall dynamics of the host-pathogen interactome. Thus, we propose that such an approach has immediate application to the rational design of brucellosis and salmonellosis vaccines. Copyright © 2011 Elsevier Ltd. All rights reserved.

Depressive symptoms and occupational stress among Chinese female nurses: the mediating effects of social support and rational coping.

PubMed

Wu, Hui; Ge, Cui Xia; Sun, Wei; Wang, Jia Na; Wang, Lie

2011-10-01

The study reported here was designed to investigate the relationship between depressive symptoms and occupational stress in female nurses in China during the period June-July 2008. The hypothesis tested was that social support and rational coping would mediate the effects of occupational stress on depressive symptoms. Our structural equation modeling revealed that social support and rational coping were negatively correlated with depressive symptoms. Social support and rational coping mediated the effects of occupational stress on depressive symptoms. Role overload, role insufficiency, and role boundary were predictive of depressive symptoms. These results indicated that lessening occupational stress and strengthening social support and rational coping could decrease depressive symptoms among Chinese female nurses. Copyright © 2011 Wiley Periodicals, Inc.

Selected approaches for rational drug design and high throughput screening to identify anti-cancer molecules.

PubMed

Hedvat, Michael; Emdad, Luni; Das, Swadesh K; Kim, Keetae; Dasgupta, Santanu; Thomas, Shibu; Hu, Bin; Zhu, Shan; Dash, Rupesh; Quinn, Bridget A; Oyesanya, Regina A; Kegelman, Timothy P; Sokhi, Upneet K; Sarkar, Siddik; Erdogan, Eda; Menezes, Mitchell E; Bhoopathi, Praveen; Wang, Xiang-Yang; Pomper, Martin G; Wei, Jun; Wu, Bainan; Stebbins, John L; Diaz, Paul W; Reed, John C; Pellecchia, Maurizio; Sarkar, Devanand; Fisher, Paul B

2012-11-01

Structure-based modeling combined with rational drug design, and high throughput screening approaches offer significant potential for identifying and developing lead compounds with therapeutic potential. The present review focuses on these two approaches using explicit examples based on specific derivatives of Gossypol generated through rational design and applications of a cancer-specificpromoter derived from Progression Elevated Gene-3. The Gossypol derivative Sabutoclax (BI-97C1) displays potent anti-tumor activity against a diverse spectrum of human tumors. The model of the docked structure of Gossypol bound to Bcl-XL provided a virtual structure-activity-relationship where appropriate modifications were predicted on a rational basis. These structure-based studies led to the isolation of Sabutoclax, an optically pure isomer of Apogossypol displaying superior efficacy and reduced toxicity. These studies illustrate the power of combining structure-based modeling with rational design to predict appropriate derivatives of lead compounds to be empirically tested and evaluated for bioactivity. Another approach to cancer drug discovery utilizes a cancer-specific promoter as readouts of the transformed state. The promoter region of Progression Elevated Gene-3 is such a promoter with cancer-specific activity. The specificity of this promoter has been exploited as a means of constructing cancer terminator viruses that selectively kill cancer cells and as a systemic imaging modality that specifically visualizes in vivo cancer growth with no background from normal tissues. Screening of small molecule inhibitors that suppress the Progression Elevated Gene-3-promoter may provide relevant lead compounds for cancer therapy that can be combined with further structure-based approaches leading to the development of novel compounds for cancer therapy.

Surface characterization of retinal tissues for the enhancement of vitreoretinal surgical methods

NASA Astrophysics Data System (ADS)

Valentin-Rodriguez, Celimar

Diabetic retinopathy is the most common ophthalmic complication of diabetes and the leading cause of blindness among adults, ages 30 to 70. Surgery to remove scar tissue in the eye is the only corrective treatment once the retina is affected. Visual recovery is often hampered by retinal trauma during surgery and by low patient compliance. Our work in this project aimed to improve vitreoretinal surgical methods from information gathered by sensitive surface analysis of pre-retinal tissues found at the vitreoretinal interface. Atomic force microscopy characterization of human retinal tissues revealed that surgically excised inner limiting membrane (ILM) has a heterogeneous surface and is mainly composed of globular and fibrous structures. ILM tissues also show low adhesion for clean unmodified surfaces as opposed to those with functional groups attractive to those on the ILM surface, due to their charge. Based on these observations, layer-by-layer films with embedded gold nanoparticles with a positive outer charge were designed. These modifications increased the adhesion between surgical instruments and ILM by increasing the roughness and tuning the film surface charge. These films proved to be stable under physiological conditions. Finally, the effect of vital dyes on the topographical characteristics of ILMs was characterized and new imaging modes to further reveal ILM topography were utilized. Roughness and adhesion force data suggest that second generation dyes have no effect on the surface nanostructure of ILMs, but increase adhesion at the tip sample interface. This project clearly illustrates that physicochemical information from tissues can be used to rationally re-design surgical procedures, in this case for tissue removal purposes. This rational design method can be applied to other soft tissue excision procedures as is the case of cataract surgery or laparoscopic removal of endometrial tissue.

Do students use contextual protective behaviors to reduce alcohol-related sexual risk? Examination of a dual-process decision-making model.

PubMed

Scaglione, Nichole M; Hultgren, Brittney A; Reavy, Racheal; Mallett, Kimberly A; Turrisi, Rob; Cleveland, Michael J; Sell, Nichole M

2015-09-01

Recent studies suggest drinking protective behaviors (DPBs) and contextual protective behaviors (CPBs) can uniquely reduce alcohol-related sexual risk in college students. Few studies have examined CPBs independently, and even fewer have utilized theory to examine modifiable psychosocial predictors of students' decisions to use CPBs. The current study used a prospective design to examine (a) rational and reactive pathways and psychosocial constructs predictive of CPB use and (b) how gender might moderate these influences in a sample of college students. Students (n = 508) completed Web-based baseline (mid-Spring semester) and 1- and 6-month follow-up assessments of CPB use; psychosocial constructs (expectancies, normative beliefs, attitudes, and self-concept); and rational and reactive pathways (intentions and willingness). Regression was used to examine rational and reactive influences as proximal predictors of CPB use at the 6-month follow-up. Subsequent path analyses examined the effects of psychosocial constructs, as distal predictors of CPB use, mediated through the rational and reactive pathways. Both rational (intentions to use CPB) and reactive (willingness to use CPB) influences were significantly associated with increased CPB use. The examined distal predictors were found to effect CPB use differentially through the rational and reactive pathways. Gender did not significantly moderate any relationships within in the model. Findings suggest potential entry points for increasing CPB use that include both rational and reactive pathways. Overall, this study demonstrates the mechanisms underlying how to increase the use of CPBs in programs designed to reduce alcohol-related sexual consequences and victimization. (c) 2015 APA, all rights reserved).

The Design of Case Products’ Shape Form Information Database Based on NURBS Surface

NASA Astrophysics Data System (ADS)

Liu, Xing; Liu, Guo-zhong; Xu, Nuo-qi; Zhang, Wei-she

2017-07-01

In order to improve the computer design of product shape design,applying the Non-uniform Rational B-splines(NURBS) of curves and surfaces surface to the representation of the product shape helps designers to design the product effectively.On the basis of the typical product image contour extraction and using Pro/Engineer(Pro/E) to extract the geometric feature of scanning mold,in order to structure the information data base system of value point,control point and node vector parameter information,this paper put forward a unified expression method of using NURBS curves and surfaces to describe products’ geometric shape and using matrix laboratory(MATLAB) to simulate when products have the same or similar function.A case study of electric vehicle’s front cover illustrates the access process of geometric shape information of case product in this paper.This method can not only greatly reduce the capacity of information debate,but also improve the effectiveness of computer aided geometric innovation modeling.

An optimal control approach to the design of moving flight simulators

NASA Technical Reports Server (NTRS)

Sivan, R.; Ish-Shalom, J.; Huang, J.-K.

1982-01-01

An abstract flight simulator design problem is formulated in the form of an optimal control problem, which is solved for the linear-quadratic-Gaussian special case using a mathematical model of the vestibular organs. The optimization criterion used is the mean-square difference between the physiological outputs of the vestibular organs of the pilot in the aircraft and the pilot in the simulator. The dynamical equations are linearized, and the output signal is modeled as a random process with rational power spectral density. The method described yields the optimal structure of the simulator's motion generator, or 'washout filter'. A two-degree-of-freedom flight simulator design, including single output simulations, is presented.

Design of open rectangular and trapezoidal channels

NASA Astrophysics Data System (ADS)

González, C. P.; Vera, P. E.; Carrillo, G.; García, S.

2018-04-01

In this work, the results of designing open channels in rectangular and trapezoidal form are presented. For the development of the same important aspects were taken as determination of flows by means of formula of the rational method, area of the surface for its implementation, optimal form of the flow to meet the needs of that environment. In the design the parameter of the hydraulic radius expressed in terms of the hydraulic area and wet perimeter was determined, considering that the surface on which the fluid flows is the product of the perimeter of the section and the length of the channel and where shear is generated by the condition of no slippage.

Discriminating between stabilizing and destabilizing protein design mutations via recombination and simulation.

PubMed

Johnson, Lucas B; Gintner, Lucas P; Park, Sehoo; Snow, Christopher D

2015-08-01

Accuracy of current computational protein design (CPD) methods is limited by inherent approximations in energy potentials and sampling. These limitations are often used to qualitatively explain design failures; however, relatively few studies provide specific examples or quantitative details that can be used to improve future CPD methods. Expanding the design method to include a library of sequences provides data that is well suited for discriminating between stabilizing and destabilizing design elements. Using thermophilic endoglucanase E1 from Acidothermus cellulolyticus as a model enzyme, we computationally designed a sequence with 60 mutations. The design sequence was rationally divided into structural blocks and recombined with the wild-type sequence. Resulting chimeras were assessed for activity and thermostability. Surprisingly, unlike previous chimera libraries, regression analysis based on one- and two-body effects was not sufficient for predicting chimera stability. Analysis of molecular dynamics simulations proved helpful in distinguishing stabilizing and destabilizing mutations. Reverting to the wild-type amino acid at destabilized sites partially regained design stability, and introducing predicted stabilizing mutations in wild-type E1 significantly enhanced thermostability. The ability to isolate stabilizing and destabilizing elements in computational design offers an opportunity to interpret previous design failures and improve future CPD methods. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Prevalence and Determinants of Physician Bedside Rationing

PubMed Central

Hurst, Samia A; Slowther, Anne-Marie; Forde, Reidun; Pegoraro, Renzo; Reiter-Theil, Stella; Perrier, Arnaud; Garrett-Mayer, Elizabeth; Danis, Marion

2006-01-01

BACKGROUND Bedside rationing by physicians is controversial. The debate, however, is clouded by lack of information regarding the extent and character of bedside rationing. DESIGN, SETTING, AND PARTICIPANTS We developed a survey instrument to examine the frequency, criteria, and strategies used for bedside rationing. Content validity was assessed through expert assessment and scales were tested for internal consistency. The questionnaire was translated and administered to General Internists in Norway, Switzerland, Italy, and the United Kingdom. Logistic regression was used to identify the variables associated with reported rationing. RESULTS Survey respondents (N =656, response rate 43%) ranged in age from 28 to 82, and averaged 25 years in practice. Most respondents (82.3%) showed some degree of agreement with rationing, and 56.3% reported that they did ration interventions. The most frequently mentioned criteria for rationing were a small expected benefit (82.3%), low chances of success (79.8%), an intervention intended to prolong life when quality of life is low (70.6%), and a patient over 85 years of age (70%). The frequency of rationing by clinicians was positively correlated with perceived scarcity of resources (odds ratio [OR]=1.11, 95% confidence interval [CI] 1.06 to 1.16), perceived pressure to ration (OR=2.14, 95% CI 1.52 to 3.01), and agreement with rationing (OR=1.13, 95% CI 1.05 to 1.23). CONCLUSION Bedside rationing is prevalent in all surveyed European countries and varies with physician attitudes and resource availability. The prevalence of physician bedside rationing, which presents physicians with difficult moral dilemmas, highlights the importance of discussions regarding how to ration care in the most ethically justifiable manner. PMID:16836629

Optimal design of piezoelectric transformers: a rational approach based on an analytical model and a deterministic global optimization.

PubMed

Pigache, Francois; Messine, Frédéric; Nogarede, Bertrand

2007-07-01

This paper deals with a deterministic and rational way to design piezoelectric transformers in radial mode. The proposed approach is based on the study of the inverse problem of design and on its reformulation as a mixed constrained global optimization problem. The methodology relies on the association of the analytical models for describing the corresponding optimization problem and on an exact global optimization software, named IBBA and developed by the second author to solve it. Numerical experiments are presented and compared in order to validate the proposed approach.

Evaluation and rational design of guide RNAs for efficient CRISPR/Cas9-mediated mutagenesis in Ciona

PubMed Central

Gandhi, Shashank; Haeussler, Maximilian; Razy-Krajka, Florian; Christiaen, Lionel; Stolfi, Alberto

2017-01-01

The CRISPR/Cas9 system has emerged as an important tool for various genome engineering applications. A current obstacle to high throughput applications of CRISPR/Cas9 is the imprecise prediction of highly active single guide RNAs (sgRNAs). We previously implemented the CRISPR/Cas9 system to induce tissue-specific mutations in the tunicate Ciona. In the present study, we designed and tested 83 single guide RNA (sgRNA) vectors targeting 23 genes expressed in the cardiopharyngeal progenitors and surrounding tissues of Ciona embryo. Using high-throughput sequencing of mutagenized alleles, we identified guide sequences that correlate with sgRNA mutagenesis activity and used this information for the rational design of all possible sgRNAs targeting the Ciona transcriptome. We also describe a one-step cloning-free protocol for the assembly of sgRNA expression cassettes. These cassettes can be directly electroporated as unpurified PCR products into Ciona embryos for sgRNA expression in vivo, resulting in high frequency of CRISPR/Cas9-mediated mutagenesis in somatic cells of electroporated embryos. We found a strong correlation between the frequency of an Ebf loss-of-function phenotype and the mutagenesis efficacies of individual Ebf-targeting sgRNAs tested using this method. We anticipate that our approach can be scaled up to systematically design and deliver highly efficient sgRNAs for the tissue-specific investigation of gene functions in Ciona. PMID:28341547

Magnetic pulse cleaning of products

NASA Astrophysics Data System (ADS)

Smolentsev, V. P.; Safonov, S. V.; Smolentsev, E. V.; Fedonin, O. N.

2016-04-01

The article deals with the application of a magnetic impact for inventing new equipment and methods of cleaning cast precision blanks from fragile or granular thickened surface coatings, which are difficult to remove and highly resistant to further mechanical processing. The issues relating to a rational use of the new method for typical products and auxiliary operations have been studied. The calculation and design methods have been elaborated for load-carrying elements of the equipment created. It has been shown, that the application of the magnetic pulse method, combined with a low-frequency vibration process is perspective at enterprises of general and special machine construction, for cleaning lightweight blanks and containers, used for transporting bulk goods.

Rationing medical education.

PubMed

Walsh, Kieran

2016-03-01

The purpose of this paper is to discuss the role of rationing in medical education. Medical education is expensive and there is a limit to that which governments, funders or individuals can spend on it. Rationing involves the allocation of resources that are limited. This paper discussed the pros and cons of the application of rationing to medical education and the different forms of rationing that could be applied. Even though some stakeholders in medical education might be taken aback at the prospect of rationing, the truth is that rationing has always occurred in one form or another in medical education and in healthcare more broadly. Different types of rationing exist in healthcare professional education. For example rationing may be implicit or explicit or may be based on macro-allocation or micro-allocation decisions. Funding can be distributed equally among learners, or according to the needs of individual learners, or to ensure that overall usefulness is maximised. One final option is to allow the market to operate freely and to decide in that way. These principles of rationing can apply to individual learners or to institutions or departments or learning modes. Rationing is occurring in medical education, even though it might be implicit. It is worth giving consideration to methods of rationing and to make thinking about rationing more explicit.

Parity for mental health and substance abuse care under managed care.

PubMed

Frank, Richard G.; McGuire, Thomas G.

1998-12-01

BACKGROUND: Parity in insurance coverage for mental health and substance abuse has been a key goal of mental health and substance abuse care advocates in the United States during most of the past 20 years. The push for parity began during the era of indemnity insurance and fee for service payment when benefit design was the main rationing device in health care. The central economic argument for enacting legislation aimed at regulating the insurance benefit was to address market failure stemming from adverse selection. The case against parity was based on inefficiency related to moral hazard. Empirical analyses provided evidence that ambulatory mental health services were considerably more responsive to the terms of insurance than were ambulatory medical services. AIMS: Our goal in this research is to reexamine the economics of parity in the light of recent changes in the delivery of health care in the United States. Specifically managed care has fundamentally altered the way in which health services are rationed. Benefit design is now only one mechanism among many that are used to allocate health care resources and control costs. We examine the implication of these changes for policies aimed at achieving parity in insurance coverage. METHOD: We develop a theoretical approach to characterizing rationing under managed care. We then analyze the traditional efficiency concerns in insurance, adverse selection and moral hazard in the context of policy aimed at regulating health and mental health benefits under private insurance. RESULTS: We show that since managed care controls costs and utilization in new ways parity in benefit design no longer implies equal access to and quality of mental health and substance abuse care. Because costs are controlled by management under managed care and not primarily by out of pocket prices paid by consumers, demand response recedes as an efficiency argument against parity. At the same time parity in benefit design may accomplish less with respect to providing a remedy to problems related to adverse selection.

A rapid and rational approach to generating isomorphous heavy-atom phasing derivatives

PubMed Central

Lu, Jinghua; Sun, Peter D.

2014-01-01

In attempts to replace the conventional trial-and-error heavy-atom derivative search method with a rational approach, we previously defined heavy metal compound reactivity against peptide ligands. Here, we assembled a composite pH and buffer-dependent peptide reactivity profile for each heavy metal compound to guide rational heavy-atom derivative search. When knowledge of the best-reacting heavy-atom compound is combined with mass spectrometry-assisted derivatization, and with a quick-soak method to optimize phasing, it is likely that the traditional heavy-atom compounds could meet the demand of modern high-throughput X-ray crystallography. As an example, we applied this rational heavy-atom phasing approach to determine a previously unknown mouse serum amyloid A2 crystal structure. PMID:25040395

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

NASA Astrophysics Data System (ADS)

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.

Toward rational design of amines for CO2 capture: Substituent effect on kinetic process for the reaction of monoethanolamine with CO2.

PubMed

Xie, Hongbin; Wang, Pan; He, Ning; Yang, Xianhai; Chen, Jingwen

2015-11-01

Amines have been considered as promising candidates for post-combustion CO2 capture. A mechanistic understanding for the chemical processes involved in the capture and release of CO2 is important for the rational design of amines. In this study, the structural effects of amines on the kinetic competition among three typical products (carbamates, carbamic acids and bicarbonate) from amines+CO2 were investigated, in contrast to previous thermodynamic studies to tune the reaction of amines with CO2 based on desirable reaction enthalpy and reaction stoichiometry. We used a quantum chemical method to calculate the activation energies (Ea) for the reactions of a range of substituted monoethanolamines with CO2 covering three pathways to the three products. The results indicate that the formation of carbamates is the most favorable, among the three considered products. In addition, we found that the Ea values for all pathways linearly correlate with pKa of amines, and more importantly, the kinetic competition between carbamate and bicarbonate absorption pathways varies with pKa of the amines, i.e. stronger basicity results in less difference in Ea. These results highlight the importance of the consideration of kinetic competition among different reaction pathways in amine design. Copyright © 2015. Published by Elsevier B.V.

Personal Autonomy and Rational Suicide.

ERIC Educational Resources Information Center

Webber, May A.; Shulman, Ernest

That certain suicides (which can be designated as rational) ought not to be interfered with is closely tied to the notion of the "right to autonomy." Specifically it is because the individual in question has this right that interference is prohibited. A proper understanding of the right to autonomy, while essential to understanding why…

The Feminist Supervision Scale: A Rational/Theoretical Approach

ERIC Educational Resources Information Center

Szymanski, Dawn M.

2003-01-01

This article reports the development and psychometric properties of the Feminist Supervision Scale (FSS), a new scale designed to assess feminist supervision practices in clinical supervision. This 32-item measure was developed using a rational/theoretical approach of test construction and includes four subscales: (a) collaborative relationships,…

Designing and developing suppository formulations for anti-HIV drug delivery.

PubMed

Ham, Anthony S; Buckheit, Robert W

2017-08-01

Despite a long history of use for rectal and vaginal drug delivery, the current worldwide market for suppositories is limited primarily due to a lack of user acceptability. Therefore, virtually no rational pharmaceutical development of antiviral suppositories has been performed. However, suppositories offer several advantages over other antiviral dosage forms. Current suppository designs have integrated active pharmaceutical ingredients into existing formulation designs without optimization. As such, emerging suppository development has been focused on improving upon the existing classical design to enhance drug delivery and is poised to open suppository drug delivery to a broader range of drugs, including antiretroviral products. Thus, with continuing research into rational suppository design and development, there is significant potential for antiretroviral suppository drug delivery.

Multitarget drug discovery projects in CNS diseases: quantitative systems pharmacology as a possible path forward.

PubMed

Geerts, Hugo; Kennis, Ludo

2014-01-01

Clinical development in brain diseases has one of the lowest success rates in the pharmaceutical industry, and many promising rationally designed single-target R&D projects fail in expensive Phase III trials. By contrast, successful older CNS drugs do have a rich pharmacology. This article will provide arguments suggesting that highly selective single-target drugs are not sufficiently powerful to restore complex neuronal circuit homeostasis. A rationally designed multitarget project can be derisked by dialing in an additional symptomatic treatment effect on top of a disease modification target. Alternatively, we expand upon a hypothetical workflow example using a humanized computer-based quantitative systems pharmacology platform. The hope is that incorporating rationally multipharmacology drug discovery could potentially lead to more impactful polypharmacy drugs.

Computer-aided rational design of the phosphotransferase system for enhanced glucose uptake in Escherichia coli

PubMed Central

Nishio, Yousuke; Usuda, Yoshihiro; Matsui, Kazuhiko; Kurata, Hiroyuki

2008-01-01

The phosphotransferase system (PTS) is the sugar transportation machinery that is widely distributed in prokaryotes and is critical for enhanced production of useful metabolites. To increase the glucose uptake rate, we propose a rational strategy for designing the molecular architecture of the Escherichia coli glucose PTS by using a computer-aided design (CAD) system and verified the simulated results with biological experiments. CAD supports construction of a biochemical map, mathematical modeling, simulation, and system analysis. Assuming that the PTS aims at controlling the glucose uptake rate, the PTS was decomposed into hierarchical modules, functional and flux modules, and the effect of changes in gene expression on the glucose uptake rate was simulated to make a rational strategy of how the gene regulatory network is engineered. Such design and analysis predicted that the mlc knockout mutant with ptsI gene overexpression would greatly increase the specific glucose uptake rate. By using biological experiments, we validated the prediction and the presented strategy, thereby enhancing the specific glucose uptake rate. PMID:18197177

Simple Methods and Rational Design for Enhancing Aptamer Sensitivity and Specificity

PubMed Central

Kalra, Priya; Dhiman, Abhijeet; Cho, William C.; Bruno, John G.; Sharma, Tarun K.

2018-01-01

Aptamers are structured nucleic acid molecules that can bind to their targets with high affinity and specificity. However, conventional SELEX (Systematic Evolution of Ligands by EXponential enrichment) methods may not necessarily produce aptamers of desired affinity and specificity. Thus, to address these questions, this perspective is intended to suggest some approaches and tips along with novel selection methods to enhance evolution of aptamers. This perspective covers latest novel innovations as well as a broad range of well-established approaches to improve the individual binding parameters (aptamer affinity, avidity, specificity and/or selectivity) of aptamers during and/or post-SELEX. The advantages and limitations of individual aptamer selection methods and post-SELEX optimizations, along with rational approaches to overcome these limitations are elucidated in each case. Further the impact of chosen selection milieus, linker-systems, aptamer cocktails and detection modules utilized in conjunction with target-specific aptamers, on the overall assay performance are discussed in detail, each with its own advantages and limitations. The simple variations suggested are easily available for facile implementation during and/or post-SELEX to develop ultrasensitive and specific assays. Finally, success studies of established aptamer-based assays are discussed, highlighting how they utilized some of the suggested methodologies to develop commercially successful point-of-care diagnostic assays. PMID:29868605

Simple Methods and Rational Design for Enhancing Aptamer Sensitivity and Specificity.

PubMed

Kalra, Priya; Dhiman, Abhijeet; Cho, William C; Bruno, John G; Sharma, Tarun K

2018-01-01

Aptamers are structured nucleic acid molecules that can bind to their targets with high affinity and specificity. However, conventional SELEX (Systematic Evolution of Ligands by EXponential enrichment) methods may not necessarily produce aptamers of desired affinity and specificity. Thus, to address these questions, this perspective is intended to suggest some approaches and tips along with novel selection methods to enhance evolution of aptamers. This perspective covers latest novel innovations as well as a broad range of well-established approaches to improve the individual binding parameters (aptamer affinity, avidity, specificity and/or selectivity) of aptamers during and/or post-SELEX. The advantages and limitations of individual aptamer selection methods and post-SELEX optimizations, along with rational approaches to overcome these limitations are elucidated in each case. Further the impact of chosen selection milieus, linker-systems, aptamer cocktails and detection modules utilized in conjunction with target-specific aptamers, on the overall assay performance are discussed in detail, each with its own advantages and limitations. The simple variations suggested are easily available for facile implementation during and/or post-SELEX to develop ultrasensitive and specific assays. Finally, success studies of established aptamer-based assays are discussed, highlighting how they utilized some of the suggested methodologies to develop commercially successful point-of-care diagnostic assays.

Fundamental understanding and rational design of high energy structural microbatteries

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

Wang, Yuxing; Li, Qiuyan; Cartmell, Samuel

Microbatteries play a critical role in determining the lifetime of downsized sensors, wearable devices and medical applications, etc. More often, structural batteries are required from the perspective of aesthetics and space utilization, which is however rarely explored. Herein, we discuss the fundamental issues associated with the rational design of practically usable high energy microbatteries. The tubular shape of the cell further allows the flexible integration of microelectronics. A functioning acoustic micro-transmitter continuously powered by this tubular battery has been successfully demonstrated. Multiple design features adopted to accommodate large mechanical stress during the rolling process are discussed providing new insights inmore » designing the structural microbatteries for emerging technologies.« less

Designing of skull defect implants using C1 rational cubic Bezier and offset curves

NASA Astrophysics Data System (ADS)

Mohamed, Najihah; Majid, Ahmad Abd; Piah, Abd Rahni Mt; Rajion, Zainul Ahmad

2015-05-01

Some of the reasons to construct skull implant are due to head trauma after an accident or an injury or an infection or because of tumor invasion or when autogenous bone is not suitable for replacement after a decompressive craniectomy (DC). The main objective of our study is to develop a simple method to redesign missing parts of the skull. The procedure begins with segmentation, data approximation, and estimation process of the outer wall by a C1 continuous curve. Its offset curve is used to generate the inner wall. A metaheuristic algorithm, called harmony search (HS) is a derivative-free real parameter optimization algorithm inspired from the musical improvisation process of searching for a perfect state of harmony. In this study, data approximation by a rational cubic Bézier function uses HS to optimize position of middle points and value of the weights. All the phases contribute significantly in making our proposed technique automated. Graphical examples of several postoperative skulls are displayed to show the effectiveness of our proposed method.

A Systematic Approach to Time-series Metabolite Profiling and RNA-seq Analysis of Chinese Hamster Ovary Cell Culture.

PubMed

Hsu, Han-Hsiu; Araki, Michihiro; Mochizuki, Masao; Hori, Yoshimi; Murata, Masahiro; Kahar, Prihardi; Yoshida, Takanobu; Hasunuma, Tomohisa; Kondo, Akihiko

2017-03-02

Chinese hamster ovary (CHO) cells are the primary host used for biopharmaceutical protein production. The engineering of CHO cells to produce higher amounts of biopharmaceuticals has been highly dependent on empirical approaches, but recent high-throughput "omics" methods are changing the situation in a rational manner. Omics data analyses using gene expression or metabolite profiling make it possible to identify key genes and metabolites in antibody production. Systematic omics approaches using different types of time-series data are expected to further enhance understanding of cellular behaviours and molecular networks for rational design of CHO cells. This study developed a systematic method for obtaining and analysing time-dependent intracellular and extracellular metabolite profiles, RNA-seq data (enzymatic mRNA levels) and cell counts from CHO cell cultures to capture an overall view of the CHO central metabolic pathway (CMP). We then calculated correlation coefficients among all the profiles and visualised the whole CMP by heatmap analysis and metabolic pathway mapping, to classify genes and metabolites together. This approach provides an efficient platform to identify key genes and metabolites in CHO cell culture.

The Golden Age of Software Architecture: A Comprehensive Survey

DTIC Science & Technology

2006-02-01

UML [14], under the leadership of (at the time) Rational, has integrated a number of design notations and developed a method for applying them...yes 97 survey, model Garlan. Research directions in SA [28] 54 yes 93 specific domains Cremer et al. The SA for scenario control in the Iowa...Environment of the Domain-Specific Software Architecture Project, ADAGE-IBM-92-11, Version 2.0, November, 1993 [23] J. Cremer , J. Kearney, Y. Papelis, and

Underground pipeline laying using the pipe-in-pipe system

NASA Astrophysics Data System (ADS)

Antropova, N.; Krets, V.; Pavlov, M.

2016-09-01

The problems of resource saving and environmental safety during the installation and operation of the underwater crossings are always relevant. The paper describes the existing methods of trenchless pipeline technology, the structure of multi-channel pipelines, the types of supporting and guiding systems. The rational design is suggested for the pipe-in-pipe system. The finite element model is presented for the most dangerous sections of the inner pipes, the optimum distance is detected between the roller supports.

Assembly of metals and nanoparticles into novel nanocomposite superstructures

PubMed Central

Xu, Jiaquan; Chen, Lianyi; Choi, Hongseok; Konish, Hiromi; Li, Xiaochun

2013-01-01

Controlled assembly of nanoscale objects into superstructures is of tremendous interests. Many approaches have been developed to fabricate organic-nanoparticle superstructures. However, effective fabrication of inorganic-nanoparticle superstructures (such as nanoparticles linked by metals) remains a difficult challenge. Here we show a novel, general method to assemble metals and nanoparticles rationally into nanocomposite superstructures. Novel metal-nanoparticle superstructures are achieved by self-assembly of liquid metals and nanoparticles in immiscible liquids driven by reduction of free energy. Superstructures with various architectures, such as metal-core/nanoparticle-shell, nanocomposite-core/nanoparticle-shell, network of metal-linked core/shell nanostructures, and network of metal-linked nanoparticles, were successfully fabricated by simply tuning the volume ratio between nanoparticles and liquid metals. Our approach provides a simple, general way for fabrication of numerous metal-nanoparticle superstructures and enables a rational design of these novel superstructures with desired architectures for exciting applications.

Advances in nanosized zeolites

NASA Astrophysics Data System (ADS)

Mintova, Svetlana; Gilson, Jean-Pierre; Valtchev, Valentin

2013-07-01

This review highlights recent developments in the synthesis of nanosized zeolites. The strategies available for their preparation (organic-template assisted, organic-template free, and alternative procedures) are discussed. Major breakthroughs achieved by the so-called zeolite crystal engineering and encompass items such as mastering and using the physicochemical properties of the precursor synthesis gel/suspension, optimizing the use of silicon and aluminium precursor sources, the rational use of organic templates and structure-directing inorganic cations, and careful adjustment of synthesis conditions (temperature, pressure, time, heating processes from conventional to microwave and sonication) are addressed. An on-going broad and deep fundamental understanding of the crystallization process, explaining the influence of all variables of this complex set of reactions, underpins an even more rational design of nanosized zeolites with exceptional properties. Finally, the advantages and limitations of these methods are addressed with particular attention to their industrial prospects and utilization in existing and advanced applications.

Modeling chemical reactions for drug design.

PubMed

Gasteiger, Johann

2007-01-01

Chemical reactions are involved at many stages of the drug design process. This starts with the analysis of biochemical pathways that are controlled by enzymes that might be downregulated in certain diseases. In the lead discovery and lead optimization process compounds have to be synthesized in order to test them for their biological activity. And finally, the metabolism of a drug has to be established. A better understanding of chemical reactions could strongly help in making the drug design process more efficient. We have developed methods for quantifying the concepts an organic chemist is using in rationalizing reaction mechanisms. These methods allow a comprehensive modeling of chemical reactivity and thus are applicable to a wide variety of chemical reactions, from gas phase reactions to biochemical pathways. They are empirical in nature and therefore allow the rapid processing of large sets of structures and reactions. We will show here how methods have been developed for the prediction of acidity values and of the regioselectivity in organic reactions, for designing the synthesis of organic molecules and of combinatorial libraries, and for furthering our understanding of enzyme-catalyzed reactions and of the metabolism of drugs.

The Rational Approach to Budget Cuts: One University's Experience. ASHE 1987 Annual Meeting Paper.

ERIC Educational Resources Information Center

Hardy, Cynthia

The experiences of the University of Montreal in using a rational-analytic framework to allocate resources at a time of budget costs are discussed. The following characteristics for rational decision-making are identified and applied to the University of Montreal: whether goals were known, whether alternative methods of resource allocation were…

Economic reasoning and artificial intelligence.

PubMed

Parkes, David C; Wellman, Michael P

2015-07-17

The field of artificial intelligence (AI) strives to build rational agents capable of perceiving the world around them and taking actions to advance specified goals. Put another way, AI researchers aim to construct a synthetic homo economicus, the mythical perfectly rational agent of neoclassical economics. We review progress toward creating this new species of machine, machina economicus, and discuss some challenges in designing AIs that can reason effectively in economic contexts. Supposing that AI succeeds in this quest, or at least comes close enough that it is useful to think about AIs in rationalistic terms, we ask how to design the rules of interaction in multi-agent systems that come to represent an economy of AIs. Theories of normative design from economics may prove more relevant for artificial agents than human agents, with AIs that better respect idealized assumptions of rationality than people, interacting through novel rules and incentive systems quite distinct from those tailored for people. Copyright © 2015, American Association for the Advancement of Science.

Residualization Rates of Near Infrared Dyes for the Rational Design of Molecular Imaging Agents

PubMed Central

Cilliers, Cornelius; Liao, Jianshan; Atangcho, Lydia; Thurber, Greg M.

2016-01-01

Purpose Near infrared (NIR) fluorescence imaging is widely used for tracking antibodies and biomolecules in vivo. Clinical and preclinical applications include intraoperative imaging, tracking therapeutics, and fluorescent labeling as a surrogate for subsequent radiolabeling. Despite their extensive use, one of the fundamental properties of NIR dyes, the residualization rate within cells following internalization, has not been systematically studied. This rate is required for the rational design of probes and proper interpretation of in vivo results. Procedures In this brief report, we measure the cellular residualization rate of eight commonly used dyes encompassing three core structures (cyanine, BODIPY, and oxazine/thiazine/carbopyronin). Results We identify residualizing (half-life > 24 hrs) and non-residualizing dyes (half-life < 24 hrs) in both the far red (~650-680 nm) and near infrared (~740-800 nm) regions. Conclusions This data will allow researchers to independently and rationally select the wavelength and residualizing nature of dyes for molecular imaging agent design. PMID:25869081

Residualization Rates of Near-Infrared Dyes for the Rational Design of Molecular Imaging Agents.

PubMed

Cilliers, Cornelius; Liao, Jianshan; Atangcho, Lydia; Thurber, Greg M

2015-12-01

Near-infrared (NIR) fluorescence imaging is widely used for tracking antibodies and biomolecules in vivo. Clinical and preclinical applications include intraoperative imaging, tracking therapeutics, and fluorescent labeling as a surrogate for subsequent radiolabeling. Despite their extensive use, one of the fundamental properties of NIR dyes, the residualization rate within cells following internalization, has not been systematically studied. This rate is required for the rational design of probes and proper interpretation of in vivo results. In this brief report, we measure the cellular residualization rate of eight commonly used dyes encompassing three core structures (cyanine, boron-dipyrromethene (BODIPY), and oxazine/thiazine/carbopyronin). We identify residualizing (half-life >24 h) and non-residualizing (half-life <24 h) dyes in both the far-red (~650-680 nm) and near-infrared (~740-800 nm) regions. This data will allow researchers to independently and rationally select the wavelength and residualizing nature of dyes for molecular imaging agent design.

A supermolecular building approach for the design and construction of metal-organic frameworks.

PubMed

Guillerm, Vincent; Kim, Dongwook; Eubank, Jarrod F; Luebke, Ryan; Liu, Xinfang; Adil, Karim; Lah, Myoung Soo; Eddaoudi, Mohamed

2014-08-21

In this review, we describe two recently implemented conceptual approaches facilitating the design and deliberate construction of metal–organic frameworks (MOFs), namely supermolecular building block (SBB) and supermolecular building layer (SBL) approaches. Our main objective is to offer an appropriate means to assist/aid chemists and material designers alike to rationally construct desired functional MOF materials, made-to-order MOFs. We introduce the concept of net-coded building units (net-cBUs), where precise embedded geometrical information codes uniquely and matchlessly a selected net, as a compelling route for the rational design of MOFs. This concept is based on employing pre-selected 0-periodic metal–organic polyhedra or 2-periodic metal–organic layers, SBBs or SBLs respectively, as a pathway to access the requisite net-cBUs. In this review, inspired by our success with the original rht-MOF, we extrapolated our strategy to other known MOFs via their deconstruction into more elaborate building units (namely polyhedra or layers) to (i) elucidate the unique relationship between edge-transitive polyhedra or layers and minimal edge-transitive 3-periodic nets, and (ii) illustrate the potential of the SBB and SBL approaches as a rational pathway for the design and construction of 3-periodic MOFs. Using this design strategy, we have also identified several new hypothetical MOFs which are synthetically targetable.

Accurate, efficient, and (iso)geometrically flexible collocation methods for phase-field models

NASA Astrophysics Data System (ADS)

Gomez, Hector; Reali, Alessandro; Sangalli, Giancarlo

2014-04-01

We propose new collocation methods for phase-field models. Our algorithms are based on isogeometric analysis, a new technology that makes use of functions from computational geometry, such as, for example, Non-Uniform Rational B-Splines (NURBS). NURBS exhibit excellent approximability and controllable global smoothness, and can represent exactly most geometries encapsulated in Computer Aided Design (CAD) models. These attributes permitted us to derive accurate, efficient, and geometrically flexible collocation methods for phase-field models. The performance of our method is demonstrated by several numerical examples of phase separation modeled by the Cahn-Hilliard equation. We feel that our method successfully combines the geometrical flexibility of finite elements with the accuracy and simplicity of pseudo-spectral collocation methods, and is a viable alternative to classical collocation methods.

Engineering in complex systems.

PubMed

Bujara, Matthias; Panke, Sven

2010-10-01

The implementation of the engineering design cycle of measure, model, manipulate would drastically enhance the success rate of biotechnological designs. Recent progress for the three elements suggests that the scope of the traditional engineering paradigm in biotechnology is expanding. Substantial advances were made in dynamic in vivo analysis of metabolism, which is essential for the accurate prediction of metabolic pathway behavior. Novel methods that require variable degrees of system knowledge facilitate metabolic system manipulation. The combinatorial testing of pre-characterized parts is particularly promising, because it can profit from automation and limits the search space. Finally, conceptual advances in orthogonalizing cells should enhance the reliability of engineering designs in the future. Coupled to improved in silico models of metabolism, these advances should allow a more rational design of metabolic systems. Copyright © 2010 Elsevier Ltd. All rights reserved.

Multifunctional Self-Assembled Monolayers for Organic Field-Effect Transistors

NASA Astrophysics Data System (ADS)

Cernetic, Nathan

Organic field effect transistors (OFETs) have the potential to reach commercialization for a wide variety of applications such as active matrix display circuitry, chemical and biological sensing, radio-frequency identification devices and flexible electronics. In order to be commercially competitive with already at-market amorphous silicon devices, OFETs need to approach similar performance levels. Significant progress has been made in developing high performance organic semiconductors and dielectric materials. Additionally, a common route to improve the performance metric of OFETs is via interface modification at the critical dielectric/semiconductor and electrode/semiconductor interface which often play a significant role in charge transport properties. These metal oxide interfaces are typically modified with rationally designed multifunctional self-assembled monolayers. As means toward improving the performance metrics of OFETs, rationally designed multifunctional self-assembled monolayers are used to explore the relationship between surface energy, SAM order, and SAM dipole on OFET performance. The studies presented within are (1) development of a multifunctional SAM capable of simultaneously modifying dielectric and metal surface while maintaining compatibility with solution processed techniques (2) exploration of the relationship between SAM dipole and anchor group on graphene transistors, and (3) development of self-assembled monolayer field-effect transistor in which the traditional thick organic semiconductor is replaced by a rationally designed self-assembled monolayer semiconductor. The findings presented within represent advancement in the understanding of the influence of self-assembled monolayers on OFETs as well as progress towards rationally designed monolayer transistors.

Effect of duration of fasting and a short-term high-roughage ration on the concentration of Escherichia coli biotype 1 in cattle feces.

PubMed

Jordan, D; McEwen, S A

1998-05-01

A field trial using cattle from a commercial feedlot was conducted to quantify the effect of duration of fasting and a temporary change in ration on the concentration of Escherichia coli biotype 1 in feces. A nested hierarchical design with repeated measures through time was used. Two groups of 20 British x European breed beef steers having reached slaughter weight (mean live weight 685 kg; SD 50 kg) were fed entirely on a high-energy ration typical of that used in the Ontario beef finishing industry or were switched for 4 days onto a high-roughage ration. This was followed by a period of fasting and water deprivation to mimic that which occurs prior to slaughter. Fecal samples were collected at 0, 24, and 48 h of fasting, and for each sample the total presumptive E. coli (biotype 1) CFU/g of feces was enumerated by spiral plating. Estimates of effect for the design factors were obtained by restricted maximum likelihood, and these were compared to robust counterparts obtained from generalized estimating equations. Results indicated that the ration, the duration of fasting, and their interaction had significant effects on total log E. coli concentration in feces. Cattle on the high-roughage ration for four days had a significantly lower initial log E. coli CFU/g of feces compared to cattle on the normal ration, but after 48 h of fasting they had a significantly higher concentration. It is concluded that while a temporary change in ration and duration of fasting does affect E. coli concentration in feces, these changes do not seem large enough to deliver a drastic improvement in beef carcass hygiene should they be incorporated in hazard analysis and critical control point (HACCP) plans for the preslaughter period of beef production.

Refusals and Rejections: Designing Messages to Serve Multiple Goals.

ERIC Educational Resources Information Center

Saeki, Mimako; O'Keefe, Barbara J.

1994-01-01

Tests a rational model of the elaboration of themes found in rejection messages, using Japanese and American participants. Finds partial support for the initial rational model but notes two key revisions: identifies two new themes in rejection messages and suggests substantial differences in the way Americans and Japanese elaborate themes to serve…

Decision-Making: Are Plants More Rational than Animals?

PubMed

Schmid, Bernhard

2016-07-25

A new study presents a novel experimental design and allows a test of risk sensitivity in plants. Faced with a choice between constant and variable resource supply, they make a rational decision for the option that maximizes fitness, a fact rarely observed in animals. Copyright © 2016 Elsevier Ltd. All rights reserved.

Joint Tactics, Techniques, and Procedures for Joint Special Operations Task Force Operations

DTIC Science & Technology

2001-12-19

phase? Is a ration cycle proposed? •• Are fresh eggs, fresh fruits and vegetables, fresh meats, juices, milk , and canned soft-drink supplements to ration...measures designed to mislead the enemy by manipulation, distortion, or falsification of evidence to induce the enemy to react in a manner prejudicial to

Calibration of the live load factor in LRFD design guidelines.

DOT National Transportation Integrated Search

2010-09-01

The Load and Resistant Factor Design (LRFD) approach is based on the concept of structural reliability. The approach is : more rational than the former design approaches such as Load Factor Design or Allowable Stress Design. The LRFD : Specification ...

Calibration of the live load factor in LRFD design guidelines : [revised].

DOT National Transportation Integrated Search

2011-07-01

The Load and Resistant Factor Design (LRFD) approach is based on the concept of structural reliability. The approach is : more rational than the former design approaches such as Load Factor Design or Allowable Stress Design. The LRFD : Specification ...

"Drug" Discovery with the Help of Organic Chemistry.

PubMed

Itoh, Yukihiro; Suzuki, Takayoshi

2017-01-01

The first step in "drug" discovery is to find compounds binding to a potential drug target. In modern medicinal chemistry, the screening of a chemical library, structure-based drug design, and ligand-based drug design, or a combination of these methods, are generally used for identifying the desired compounds. However, they do not necessarily lead to success and there is no infallible method for drug discovery. Therefore, it is important to explore medicinal chemistry based on not only the conventional methods but also new ideas. So far, we have found various compounds as drug candidates. In these studies, some strategies based on organic chemistry have allowed us to find drug candidates, through 1) construction of a focused library using organic reactions and 2) rational design of enzyme inhibitors based on chemical reactions catalyzed by the target enzyme. Medicinal chemistry based on organic chemical reactions could be expected to supplement the conventional methods. In this review, we present drug discovery with the help of organic chemistry showing examples of our explorative studies on histone deacetylase inhibitors and lysine-specific demethylase 1 inhibitors.

Biomimicry in metal-organic materials

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

Zhang, MW; Gu, ZY; Bosch, M

2015-06-15

Nature has evolved a great number of biological molecules which serve as excellent constructional or functional units for metal-organic materials (MOMs). Even though the study of biomimetic MOMs is still at its embryonic stage, considerable progress has been made in the past few years. In this critical review, we will highlight the recent advances in the design, development and application of biomimetic MOMs, and illustrate how the incorporation of biological components into MOMs could further enrich their structural and functional diversity. More importantly, this review will provide a systematic overview of different methods for rational design of MOMs with biomimeticmore » features. Published by Elsevier B.V.« less

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

PubMed

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.

Recent advances in medicinal chemistry of sulfonamides. Rational design as anti-tumoral, anti-bacterial and anti-inflammatory agents.

PubMed

Shah, Syed Shoaib Ahmad; Rivera, Gildardo; Ashfaq, Muhammad

2013-01-01

Now-a-days, cancer is becoming one of the major problems of public health in the world. Pharmacology treatment is a way to increase quality and long life. Predominantly, in last decade sulfonamide derivatives have been described as potential carbonic anhydrase inhibitors. In the present work, we describe recent advances during the last decade in medicinal chemistry of sulfonamides derivatives with some examples of rational design as anti-tumoral, antibacterial and anti-inflammatory agents. We show strategy design, structure-activity relationship, biological activity and advances of new sulfonamide compounds that have more health significance than some clinically used sulfonamides.

Sexual harassment in healthcare: classification of harassers and rationalizations of sex-based harassment behavior.

PubMed

Madison, J; Minichiello, V

2001-11-01

This study identified how 16 Australian registered nurses classified sex-based harassers and explained their own behavior and the behavior of the harasser. A qualitative research design, relying on in-depth interviews, was used to collect the data. The study found that harassment is linked to gender roles and that the harassed are reluctant to blame the harasser--the harassed had "sound" rationalizations for harassment. Awareness of the interactional dynamics of self-blame and these rationalizations will help nurse executives ensure a harassment-free workplace.

Fair and Square Computation of Inverse "Z"-Transforms of Rational Functions

ERIC Educational Resources Information Center

Moreira, M. V.; Basilio, J. C.

2012-01-01

All methods presented in textbooks for computing inverse "Z"-transforms of rational functions have some limitation: 1) the direct division method does not, in general, provide enough information to derive an analytical expression for the time-domain sequence "x"("k") whose "Z"-transform is "X"("z"); 2) computation using the inversion integral…

Simulation technology - A key to effective man-machine integration for future combat rotorcraft systems

NASA Technical Reports Server (NTRS)

Kerr, Andrew W.

1990-01-01

The utilization of advanced simulation technology in the development of the non-real-time MANPRINT design tools in the Army/NASA Aircrew-Aircraft Integration (A3I) program is described. A description is then given of the Crew Station Research and Development Facilities, the primary tool for the application of MANPRINT principles. The purpose of the A3I program is to develop a rational, predictive methodology for helicopter cockpit system design that integrates human factors engineering with other principles at an early stage in the development process, avoiding the high cost of previous system design methods. Enabling technologies such as the MIDAS work station are examined, and the potential of low-cost parallel-processing systems is indicated.

Protein mechanics: from single molecules to functional biomaterials.

PubMed

Li, Hongbin; Cao, Yi

2010-10-19

Elastomeric proteins act as the essential functional units in a wide variety of biomechanical machinery and serve as the basic building blocks for biological materials that exhibit superb mechanical properties. These proteins provide the desired elasticity, mechanical strength, resilience, and toughness within these materials. Understanding the mechanical properties of elastomeric protein-based biomaterials is a multiscale problem spanning from the atomistic/molecular level to the macroscopic level. Uncovering the design principles of individual elastomeric building blocks is critical both for the scientific understanding of multiscale mechanics of biomaterials and for the rational engineering of novel biomaterials with desirable mechanical properties. The development of single-molecule force spectroscopy techniques has provided methods for characterizing mechanical properties of elastomeric proteins one molecule at a time. Single-molecule atomic force microscopy (AFM) is uniquely suited to this purpose. Molecular dynamic simulations, protein engineering techniques, and single-molecule AFM study have collectively revealed tremendous insights into the molecular design of single elastomeric proteins, which can guide the design and engineering of elastomeric proteins with tailored mechanical properties. Researchers are focusing experimental efforts toward engineering artificial elastomeric proteins with mechanical properties that mimic or even surpass those of natural elastomeric proteins. In this Account, we summarize our recent experimental efforts to engineer novel artificial elastomeric proteins and develop general and rational methodologies to tune the nanomechanical properties of elastomeric proteins at the single-molecule level. We focus on general design principles used for enhancing the mechanical stability of proteins. These principles include the development of metal-chelation-based general methodology, strategies to control the unfolding hierarchy of multidomain elastomeric proteins, and the design of novel elastomeric proteins that exhibit stimuli-responsive mechanical properties. Moving forward, we are now exploring the use of these artificial elastomeric proteins as building blocks of protein-based biomaterials. Ultimately, we would like to rationally tailor mechanical properties of elastomeric protein-based materials by programming the molecular sequence, and thus nanomechanical properties, of elastomeric proteins at the single-molecule level. This step would help bridge the gap between single protein mechanics and material biomechanics, revealing how the mechanical properties of individual elastomeric proteins are translated into the properties of macroscopic materials.

Cognitive Rationalizations for Tanning-Bed Use: A Preliminary Exploration

PubMed Central

Banerjee, Smita C.; Hay, Jennifer L.; Greene, Kathryn

2016-01-01

Objectives To examine construct and predictive utility of an adapted cognitive rationalization scale for tanning-bed use. Methods Current/former tanning-bed-using undergraduate students (N = 216; 87.6% females; 78.4% white) at a large northeastern university participated in a survey. A cognitive rationalization for tanning-bed use scale was adapted. Standardized self-report measures of past tanning-bed use, advantages of tanning, perceived vulnerability to photoaging, tanning-bed use dependence, and tanning- bed use intention were also administered. Results The cognitive rationalization scale exhibited strong construct and predictive validity. Current tanners and tanning-bed-use-dependent participants endorsed rationalizations more strongly than did former tanners and not-tanning-bed-use-dependent participants respectively. Conclusions Findings indicate that cognitive rationalizations help explain discrepancy between inconsistent cognitions. PMID:23985280

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

PubMed

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.

Fundamental understanding and rational design of high energy structural microbatteries

DOE PAGES

Wang, Yuxing; Li, Qiuyan; Cartmell, Samuel; ...

2017-11-21

We present that microbatteries play a critical role in determining the lifetime of downsized sensors, wearable devices, medical applications, and animal acoustic telemetry transmitters among others. More often, structural batteries are required from the perspective of aesthetics and space utilization, which is however rarely explored. Herein, we discuss the fundamental issues associated with the rational design of practically usable high energy microbatteries. The tubular shape of the cell further allows the flexible integration of microelectronics. A functioning acoustic micro-transmitter continuously powered by this tubular battery has been successfully demonstrated. Finally, multiple design features adopted to accommodate large mechanical stress duringmore » the rolling process are discussed providing new insights in designing the structural microbatteries for emerging technologies.« less

Fundamental understanding and rational design of high energy structural microbatteries

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

Wang, Yuxing; Li, Qiuyan; Cartmell, Samuel

We present that microbatteries play a critical role in determining the lifetime of downsized sensors, wearable devices, medical applications, and animal acoustic telemetry transmitters among others. More often, structural batteries are required from the perspective of aesthetics and space utilization, which is however rarely explored. Herein, we discuss the fundamental issues associated with the rational design of practically usable high energy microbatteries. The tubular shape of the cell further allows the flexible integration of microelectronics. A functioning acoustic micro-transmitter continuously powered by this tubular battery has been successfully demonstrated. Finally, multiple design features adopted to accommodate large mechanical stress duringmore » the rolling process are discussed providing new insights in designing the structural microbatteries for emerging technologies.« less

Facile one-step construction of covalently networked, self-healable, and transparent superhydrophobic composite films

NASA Astrophysics Data System (ADS)

Lee, Yujin; You, Eun-Ah; Ha, Young-Geun

2018-07-01

Despite the considerable demand for bioinspired superhydrophobic surfaces with highly transparent, self-cleaning, and self-healable properties, a facile and scalable fabrication method for multifunctional superhydrophobic films with strong chemical networks has rarely been established. Here, we report a rationally designed facile one-step construction of covalently networked, transparent, self-cleaning, and self-healable superhydrophobic films via a one-step preparation and single-reaction process of multi-components. As coating materials for achieving the one-step fabrication of multifunctional superhydrophobic films, we included two different sizes of Al2O3 nanoparticles for hierarchical micro/nano dual-scale structures and transparent films, fluoroalkylsilane for both low surface energy and covalent binding functions, and aluminum nitrate for aluminum oxide networked films. On the basis of stability tests for the robust film composition, the optimized, covalently linked superhydrophobic composite films with a high water contact angle (>160°) and low sliding angle (<1°) showed excellent thermal stability (up to 400 °C), transparency (≈80%), self-healing, self-cleaning, and waterproof abilities. Therefore, the rationally designed, covalently networked superhydrophobic composite films, fabricated via a one-step solution-based process, can be further utilized for various optical and optoelectronic applications.

Identification of protein-ligand binding sites by the level-set variational implicit-solvent approach.

PubMed

Guo, Zuojun; Li, Bo; Cheng, Li-Tien; Zhou, Shenggao; McCammon, J Andrew; Che, Jianwei

2015-02-10

Protein–ligand binding is a key biological process at the molecular level. The identification and characterization of small-molecule binding sites on therapeutically relevant proteins have tremendous implications for target evaluation and rational drug design. In this work, we used the recently developed level-set variational implicit-solvent model (VISM) with the Coulomb field approximation (CFA) to locate and characterize potential protein–small-molecule binding sites. We applied our method to a data set of 515 protein–ligand complexes and found that 96.9% of the cocrystallized ligands bind to the VISM-CFA-identified pockets and that 71.8% of the identified pockets are occupied by cocrystallized ligands. For 228 tight-binding protein–ligand complexes (i.e, complexes with experimental pKd values larger than 6), 99.1% of the cocrystallized ligands are in the VISM-CFA-identified pockets. In addition, it was found that the ligand binding orientations are consistent with the hydrophilic and hydrophobic descriptions provided by VISM. Quantitative characterization of binding pockets with topological and physicochemical parameters was used to assess the “ligandability” of the pockets. The results illustrate the key interactions between ligands and receptors and can be very informative for rational drug design.

Insights into the regioselectivity and RNA-binding affinity of HIV-1 nucleocapsid protein from linear-scaling quantum methods.

PubMed

Khandogin, Jana; Musier-Forsyth, Karin; York, Darrin M

2003-07-25

Human immunodeficiency virus type 1 (HIV-1) nucleocapsid protein (NC) plays several important roles in the viral life-cycle and presents an attractive target for rational drug design. Here, the macromolecular reactivity of NC and its binding to RNA is characterized through determination of electrostatic and chemical descriptors derived from linear-scaling quantum calculations in solution. The computational results offer a rationale for the experimentally observed susceptibility of the Cys49 thiolate toward small-molecule electrophilic agents, and support the recently proposed stepwise protonation mechanism of the C-terminal Zn-coordination complex. The distinctive binding mode of NC to SL2 and SL3 stem-loops of the HIV-1 genomic RNA packaging signal is studied on the basis of protein side-chain contributions to the electrostatic binding energies. These results indicate the importance of several basic residues in the 3(10) helical region and the N-terminal zinc finger, and rationalize the presence of several evolutionarily conserved residues in NC. The combined reactivity and RNA-binding study provides new insights that may contribute toward the structure-based design of anti-HIV therapies.

Modern Technologies for Creating Synthetic Antibodies for Clinical application

PubMed Central

Lebedenko, E. N.

2009-01-01

The modular structure and versatility of antibodies enables one to modify natural immunoglobulins in different ways for various clinical applications. Rational design and molecular engineering make it possible to directionally modify the molecular size, affinity, specificity, and immunogenicity and effector functions of an antibody, as well as to combine them with other functional agents. This review focuses on up-to-date methods of antibody engineering for diagnosing and treating various diseases, particularly on new technologies meant to refine the effector functions of therapeutic antibodies. PMID:22649585

Advances in drying: Volume 4

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

Mujumdar, A.S.

1987-01-01

Topics covered in this volume include recent thoughts in modeling of drying phenomena, use of computers in rational design of drying particulates, recent advances in drying of wood, and heat/mass transfer phenomena in drying of solids. As the readers will no doubt notice, special effort is made to ensure the truly international nature of the contents of this serial publication. As existing knowledge on drying and dryers becomes more widely and readily accessible, it is expected that more and more dryers will be designed rationally rather than built solely with the benefit of empiricism.

Crystals of Human Serum Albumin for Use in Genetic Engineering and Rational Drug Design

NASA Technical Reports Server (NTRS)

Carter, Daniel C. (Inventor)

1994-01-01

This invention pertains to crystals of serum albumin and processes for growing them. The purpose of the invention is to provide crystals of serum albumin which can be studied to determine binding sites for drugs. Form 2 crystals grow in the monoclinic space P2(sub 1), and possesses the following unit cell constraints: a = 58.9 +/- 7, b = 88.3 +/- 7, c = 60.7 +/- 7, Beta = 101.0 +/- 2 degrees. One advantage of the invention is that it will allow rational drug design

Testing the limits of rational design by engineering pH sensitivity into membrane-active peptides.

PubMed

Wiedman, Gregory; Wimley, William C; Hristova, Kalina

2015-04-01

In this work, we sought to rationally design membrane-active peptides that are triggered by low pH to form macromolecular-sized pores in lipid bilayers. Such peptides could have broad utility in biotechnology and in nanomedicine as cancer therapeutics or drug delivery vehicles that promote release of macromolecules from endosomes. Our approach to rational design was to combine the properties of a pH-independent peptide, MelP5, which forms large pores allowing passage of macromolecules, with the properties of two pH-dependent membrane-active peptides, pHlip and GALA. We created two hybrid sequences, MelP5_Δ4 and MelP5_Δ6, by using the distribution of acidic residues on pHlip and GALA as a guide to insert acidic amino acids into the amphipathic helix of MelP5. We show that the new peptides bind to lipid bilayers and acquire secondary structure in a pH-dependent manner. The peptides also destabilize bilayers in a pH-dependent manner, such that lipid vesicles release the small molecules ANTS/DPX at low pH only. Thus, we were successful in designing pH-triggered pore-forming peptides. However, no macromolecular release was observed under any conditions. Therefore, we abolished the unique macromolecular poration properties of MelP5 by introducing pH sensitivity into its sequence. We conclude that the properties of pHlip, GALA, and MelP5 are additive, but only partially so. We propose that this lack of additivity is a limitation in the rational design of novel membrane-active peptides, and that high-throughput approaches to discovery will be critical for continued progress in the field. Copyright © 2015 Elsevier B.V. All rights reserved.

Knowledge Utilization Strategies in the Design and Implementation of New Schools--Symbolic Functions.

ERIC Educational Resources Information Center

Sieber, Sam D.

An examination of case studies suggests that rational processes were not entirely at work in the planning and conception of new, innovative schools. The rational model that serves as the foundation of our information systems assumes that a compelling professional need triggers a search for solutions; and, therefore, school personnel are eager to…

Reliability-based evaluation of bridge components for consistent safety margins.

DOT National Transportation Integrated Search

2010-10-01

The Load and Resistant Factor Design (LRFD) approach is based on the concept of structural reliability. The approach is more : rational than the former design approaches such as Load Factor Design or Allowable Stress Design. The LRFD Specification fo...

Computing the Partial Fraction Decomposition of Rational Functions with Irreducible Quadratic Factors in the Denominators

ERIC Educational Resources Information Center

Man, Yiu-Kwong

2012-01-01

In this note, a new method for computing the partial fraction decomposition of rational functions with irreducible quadratic factors in the denominators is presented. This method involves polynomial divisions and substitutions only, without having to solve for the complex roots of the irreducible quadratic polynomial or to solve a system of linear…

The Analytic Structures of Dynamical Systems.

DTIC Science & Technology

1986-01-01

equations , rational solutions, and the Painlev6 property for the Kadomtsev - Petviashvili and Hirota-Satsuma equations ", J. Math. Phys. 26 2174 (1985) 5...of rational solutions. This also obtains the Lax pairs for the modified equations . In this paper we apply this method to the Kadomtsev - Petviashvili ...3 . . . . .. .. ," ,",,....". . ".’..’.-.: -.... ., Modified equations , rational solutions, and the Painlev6 property for the Kadomtsev

Decision Making Analysis: Critical Factors-Based Methodology

DTIC Science & Technology

2010-04-01

the pitfalls associated with current wargaming methods such as assuming a western view of rational values in decision - making regardless of the cultures...Utilization theory slightly expands the rational decision making model as it states that “actors try to maximize their expected utility by weighing the...items to categorize the decision - making behavior of political leaders which tend to demonstrate either a rational or cognitive leaning. Leaders

Evaluation and rational design of guide RNAs for efficient CRISPR/Cas9-mediated mutagenesis in Ciona.

PubMed

Gandhi, Shashank; Haeussler, Maximilian; Razy-Krajka, Florian; Christiaen, Lionel; Stolfi, Alberto

2017-05-01

The CRISPR/Cas9 system has emerged as an important tool for various genome engineering applications. A current obstacle to high throughput applications of CRISPR/Cas9 is the imprecise prediction of highly active single guide RNAs (sgRNAs). We previously implemented the CRISPR/Cas9 system to induce tissue-specific mutations in the tunicate Ciona. In the present study, we designed and tested 83 single guide RNA (sgRNA) vectors targeting 23 genes expressed in the cardiopharyngeal progenitors and surrounding tissues of Ciona embryo. Using high-throughput sequencing of mutagenized alleles, we identified guide sequences that correlate with sgRNA mutagenesis activity and used this information for the rational design of all possible sgRNAs targeting the Ciona transcriptome. We also describe a one-step cloning-free protocol for the assembly of sgRNA expression cassettes. These cassettes can be directly electroporated as unpurified PCR products into Ciona embryos for sgRNA expression in vivo, resulting in high frequency of CRISPR/Cas9-mediated mutagenesis in somatic cells of electroporated embryos. We found a strong correlation between the frequency of an Ebf loss-of-function phenotype and the mutagenesis efficacies of individual Ebf-targeting sgRNAs tested using this method. We anticipate that our approach can be scaled up to systematically design and deliver highly efficient sgRNAs for the tissue-specific investigation of gene functions in Ciona. Copyright © 2017 Elsevier Inc. All rights reserved.

Automatic Design of Digital Synthetic Gene Circuits

PubMed Central

Marchisio, Mario A.; Stelling, Jörg

2011-01-01

De novo computational design of synthetic gene circuits that achieve well-defined target functions is a hard task. Existing, brute-force approaches run optimization algorithms on the structure and on the kinetic parameter values of the network. However, more direct rational methods for automatic circuit design are lacking. Focusing on digital synthetic gene circuits, we developed a methodology and a corresponding tool for in silico automatic design. For a given truth table that specifies a circuit's input–output relations, our algorithm generates and ranks several possible circuit schemes without the need for any optimization. Logic behavior is reproduced by the action of regulatory factors and chemicals on the promoters and on the ribosome binding sites of biological Boolean gates. Simulations of circuits with up to four inputs show a faithful and unequivocal truth table representation, even under parametric perturbations and stochastic noise. A comparison with already implemented circuits, in addition, reveals the potential for simpler designs with the same function. Therefore, we expect the method to help both in devising new circuits and in simplifying existing solutions. PMID:21399700

New Technical Solution for Vertical Shaft Equipping Using Steel Headframe of Multifunction Purpose

NASA Astrophysics Data System (ADS)

Kassikhina, Elena; Pershin, Vladimir; Glazkov, Yurij

2017-11-01

The article reviews a novel approach to the design of steel angle headframe for vertical shafts of coal and ore mines on the basis of rational design solutions. Practice of construction of coal and ore mines provides application of various designs for steel angle headframes which are divided into separate large assembly blocks and constructive elements during assembling operations. Design of these blocks and elements, their weight and dimensions effect the chose of the method of assembling on which economic and technological indicators, as well as duration of down-time, depend on during performance of construction operations in shaft. The technical solution on equipment provision for mine vertical shaft using headframe of multifunctional purpose will allow changing the management construction of vertical shaft. The constructive design of the headgear allows application of the effective method of assembly and thus to provide improvement of the technical and economic indexes, and high calendar time rate of the shaft construction due to reduction of duration of works on equipment provision for the shaft and to refurbishment of the shaft in order to carry out horizontal mining.

Rational design of class I MHC ligands

NASA Astrophysics Data System (ADS)

Rognan, D.; Scapozza, L.; Folkers, G.; Daser, Angelika

1995-04-01

From the knowledge of the three-dimensional structure of a class I MHC protein, several non natural peptides were designed in order to either optimize the interactions of one secondary anchor amino acid with its HLA binding pocket or to substitute the non interacting part with spacer residues. All peptides were synthesized and tested for binding to the class I MHC protein in an in vitro reconstitution assay. As predicted, the non natural peptides present an enhanced binding to the HLA-B27 molecule with respect to their natural parent peptides. This study constitutes the first step towards the rational design of non peptidic MHC ligands that should be very promising tools for the selective immunotherapy of autoimmune diseases.

Towards the rational design of the Py5-ligand framework for ruthenium-based water oxidation catalysts.

PubMed

Schilling, Mauro; Böhler, Michael; Luber, Sandra

2018-05-21

In order to rationally design water oxidation catalysts (WOCs), an in-depth understanding of the reaction mechanism is essential. In this study we showcase the complexity of catalytic water oxidation, by elucidating how modifications of the pentapyridyl (Py5) ligand-framework influence the thermodynamics and kinetics of the process. In the reaction mechanism the pyridine-water exchange was identified as a key reaction which appears to determine the reactivity of the Py5-WOCs. Exploring the capabilities of in silico design we show which modifications of the ligand framework appear promising when attempting to improve the catalytic performance of WOCs derived from Py5.

GHM method for obtaining rationalsolutions of nonlinear differential equations.

PubMed

Vazquez-Leal, Hector; Sarmiento-Reyes, Arturo

2015-01-01

In this paper, we propose the application of the general homotopy method (GHM) to obtain rational solutions of nonlinear differential equations. It delivers a high precision representation of the nonlinear differential equation using a few linear algebraic terms. In order to assess the benefits of this proposal, three nonlinear problems are solved and compared against other semi-analytic methods or numerical methods. The obtained results show that GHM is a powerful tool, capable to generate highly accurate rational solutions. AMS subject classification 34L30.

Cofactor specificity switch in Shikimate dehydrogenase by rational design and consensus engineering.

PubMed

García-Guevara, Fernando; Bravo, Iris; Martínez-Anaya, Claudia; Segovia, Lorenzo

2017-08-01

Consensus engineering has been used to design more stable variants using the most frequent amino acid at each site of a multiple sequence alignment; sometimes consensus engineering modifies function, but efforts have mainly been focused on studying stability. Here we constructed a consensus Rossmann domain for the Shikimate dehydrogenase enzyme; separately we decided to switch the cofactor specificity through rational design in the Escherichia coli Shikimate dehydrogenase enzyme and then analyzed the effect of consensus mutations on top of our design. We found that consensus mutations closest to the 2' adenine moiety increased the activity in our design. Consensus engineering has been shown to result in more stable proteins and our findings suggest it could also be used as a complementary tool for increasing or modifying enzyme activity during design. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The mathematical statement for the solving of the problem of N-version software system design

NASA Astrophysics Data System (ADS)

Kovalev, I. V.; Kovalev, D. I.; Zelenkov, P. V.; Voroshilova, A. A.

2015-10-01

The N-version programming, as a methodology of the fault-tolerant software systems design, allows successful solving of the mentioned tasks. The use of N-version programming approach turns out to be effective, since the system is constructed out of several parallel executed versions of some software module. Those versions are written to meet the same specification but by different programmers. The problem of developing an optimal structure of N-version software system presents a kind of very complex optimization problem. This causes the use of deterministic optimization methods inappropriate for solving the stated problem. In this view, exploiting heuristic strategies looks more rational. In the field of pseudo-Boolean optimization theory, the so called method of varied probabilities (MVP) has been developed to solve problems with a large dimensionality.

[Priority setting and bedside rationing: a discussion of empirical findings].

PubMed

Strech, Daniel

2011-01-01

In addition to empirical forecasts on the extent of the current and future limitations on health care resources, empirical data on the status quo of bedside rationing play a significant role in developing suitable alternatives in dealing with limited financial resources. This article presents and discusses selected results of the international and German survey research on bedside rationing. Survey studies among physicians could prove world-wide that rationing decisions are made already today by individual physicians in the in- and out-patient services. In German hospitals, rationing is also a wide-spread though non-transparent and not (yet) very common phenomenon for an individual physician. Varying criteria for bedside rationing contribute to the fact that the current approach to bedside rationing leads to dissatisfaction on the part of physicians and to a potential disadvantage of certain patient groups. Explicit, i.e. transparent and systematic, ways of rationing could remedy these deficiencies and are therefore clearly preferable in this context. However, further specification of the methods of explicit rationing and a critical evaluation of their application in practice are needed. Moreover, it is mainly the quality of the underlying evidence that determines whether or not the actual decisions become more reasonable and fair by means of more explicit rationing approaches. Copyright © 2011 S. Karger AG, Basel.

Structure-based design of novel chemical modification of the 3'-overhang for optimization of short interfering RNA performance.

PubMed

Xu, Lexing; Wang, Xin; He, Hongwei; Zhou, Jinming; Li, Xiaoyu; Ma, Hongtao; Li, Zelin; Zeng, Yi; Shao, Rongguang; Cen, Shan; Wang, Yucheng

2015-02-10

Short interfering RNAs (siRNAs) are broadly used to manipulate gene expression in mammalian cells. Although chemical modification is useful for increasing the potency of siRNAs in vivo, rational optimization of siRNA performance through chemical modification is still a challenge. In this work, we designed and synthesized a set of siRNAs containing modified two-nucleotide 3'-overhangs with the aim of strengthening the interaction between the 3'-end of the siRNA strand and the PAZ domain of Ago2. Their efficiency of binding to the PAZ domain was calculated using a computer modeling program, followed by measurement of RNA-Ago2 interaction in a surface plasmon resonance biochemical assay. The results suggest that increasing the level of binding of the 3'-end of the guiding strand with the PAZ domain, and/or reducing the level of binding of the sense strand through modifying the two-nucleotide 3'-overhangs, affects preferential strand selection and improves siRNA activity, while we cannot exclude the possibility that the modifications at the 3'-end of the sense strand may also affect the recognition of the 5'-end of the guiding strand by the MID domain. Taken together, our work presents a strategy for optimizing siRNA performance through asymmetric chemical modification of 3'-overhangs and also helps to develop the computer modeling method for rational siRNA design.

Design of a thermally controlled sequence of triazolinedione-based click and transclick reactions† †Electronic supplementary information (ESI) available: Additional figures, experimental details, synthesis and analysis of all the model compounds and polymers, computational methods and relevant theoretical data. See DOI: 10.1039/c7sc00119c Click here for additional data file.

PubMed Central

Houck, Hannes A.; De Bruycker, Kevin; Billiet, Stijn; Dhanis, Bastiaan; Goossens, Hannelore; Catak, Saron; Van Speybroeck, Veronique

2017-01-01

The reaction of triazolinediones (TADs) and indoles is of particular interest for polymer chemistry applications, as it is a very fast and irreversible additive-free process at room temperature, but can be turned into a dynamic covalent bond forming process at elevated temperatures, giving a reliable bond exchange or ‘transclick’ reaction. In this paper, we report an in-depth study aimed at controlling the TAD–indole reversible click reactions through rational design of modified indole reaction partners. This has resulted in the identification of a novel class of easily accessible indole derivatives that give dynamic TAD-adduct formation at significantly lower temperatures. We further demonstrate that these new substrates can be used to design a directed cascade of click reactions of a functionalized TAD moiety from an initial indole reaction partner to a second indole, and finally to an irreversible reaction partner. This controlled sequence of click and transclick reactions of a single TAD reagent between three different substrates has been demonstrated both on small molecule and macromolecular level, and the factors that control the reversibility profiles have been rationalized and guided by mechanistic considerations supported by theoretical calculations. PMID:28507685

Rationality and drug use: an experimental approach.

PubMed

Blondel, Serge; Lohéac, Youenn; Rinaudo, Stéphane

2007-05-01

In rational addiction theory, higher discount rates encourage drug use. We test this hypothesis in the general framework of rationality and behaviour under risk. We do so using an experimental design with real monetary incentives. The decisions of 34 drug addicts are compared with those of a control group. The decisions of drug users (DU) are not any less consistent with standard theories of behaviour over time and under risk. Further, there is no difference in the estimated discount rate between drug users and the control group, but the former do appear to be more risk-seeking.

Rational tuning of high-energy visible light absorption for panchromatic small molecules by a two-dimensional conjugation approach

DOE PAGES

He, B.; Zherebetskyy, D.; Wang, H.; ...

2016-02-29

We have demonstrated a rational two-dimensional (2D) conjugation approach towards achieving panchromatic absorption of small molecules. Furthermore, by extending the conjugation on two orthogonal axes of an electron acceptor, namely, bay-annulated indigo (BAI), the optical absorptions could be tuned independently in both high- and low-energy regions. The unconventional modulation of the high-energy absorption is rationalized by density functional theory (DFT) calculations. Finally, we determine that a 2D tuning strategy provides novel guidelines for the design of molecular materials with tailored optoelectronic properties.

Toward a rational, value-based drug benefit for Medicare.

PubMed

Lopert, Ruth; Moon, Marilyn

2007-01-01

A major challenge facing Congress is what changes, if any, to make to Medicare Part D. With the apparent failure of the Democrats' attempt to remove the prohibition on government intervention in drug price negotiations, the party's next steps are unclear. One suggested option is a plan administered by the Centers for Medicare and Medicaid Services (CMS), to compete with private plans and facilitate a transition to a more rational structure. We discuss issues surrounding the design of such a mechanism and how it might provide a transition toward a more rational and sustainable drug benefit in the longer term.

Rainfall-runoff modeling of the Chapel Branch Creek Watershed using GIS-based rational and SCS-CN methods

Treesearch

Elizabeth N. Mihalik; Norm S. Levine; Devendra M. Amatya

2008-01-01

Chapel Branch Creek (CBC), located within the Town of Santee adjacent to Lake Marion in Orangeburg County, SC, is listed on the SC 2004 303(d) list of impaired waterbodies due to elevated levels of nitrogen (N), phosphorus (P), chlorophyll-a, and pH. In this study, using a GIS-based approach, two runoff modeling methods, the Rational and SCS-CN methods, have been...

[Computational chemistry in structure-based drug design].

PubMed

Cao, Ran; Li, Wei; Sun, Han-Zi; Zhou, Yu; Huang, Niu

2013-07-01

Today, the understanding of the sequence and structure of biologically relevant targets is growing rapidly and researchers from many disciplines, physics and computational science in particular, are making significant contributions to modern biology and drug discovery. However, it remains challenging to rationally design small molecular ligands with desired biological characteristics based on the structural information of the drug targets, which demands more accurate calculation of ligand binding free-energy. With the rapid advances in computer power and extensive efforts in algorithm development, physics-based computational chemistry approaches have played more important roles in structure-based drug design. Here we reviewed the newly developed computational chemistry methods in structure-based drug design as well as the elegant applications, including binding-site druggability assessment, large scale virtual screening of chemical database, and lead compound optimization. Importantly, here we address the current bottlenecks and propose practical solutions.

A polymer dataset for accelerated property prediction and design.

PubMed

Huan, Tran Doan; Mannodi-Kanakkithodi, Arun; Kim, Chiho; Sharma, Vinit; Pilania, Ghanshyam; Ramprasad, Rampi

2016-03-01

Emerging computation- and data-driven approaches are particularly useful for rationally designing materials with targeted properties. Generally, these approaches rely on identifying structure-property relationships by learning from a dataset of sufficiently large number of relevant materials. The learned information can then be used to predict the properties of materials not already in the dataset, thus accelerating the materials design. Herein, we develop a dataset of 1,073 polymers and related materials and make it available at http://khazana.uconn.edu/. This dataset is uniformly prepared using first-principles calculations with structures obtained either from other sources or by using structure search methods. Because the immediate target of this work is to assist the design of high dielectric constant polymers, it is initially designed to include the optimized structures, atomization energies, band gaps, and dielectric constants. It will be progressively expanded by accumulating new materials and including additional properties calculated for the optimized structures provided.

Gleaning Insights from Fecal Microbiota Transplantation and Probiotic Studies for the Rational Design of Combination Microbial Therapies

PubMed Central

Hudson, Lauren E.; Anderson, Sarah E.; Corbett, Anita H.

2016-01-01

SUMMARY Beneficial microorganisms hold promise for the treatment of numerous gastrointestinal diseases. The transfer of whole microbiota via fecal transplantation has already been shown to ameliorate the severity of diseases such as Clostridium difficile infection, inflammatory bowel disease, and others. However, the exact mechanisms of fecal microbiota transplant efficacy and the particular strains conferring this benefit are still unclear. Rationally designed combinations of microbial preparations may enable more efficient and effective treatment approaches tailored to particular diseases. Here we use an infectious disease, C. difficile infection, and an inflammatory disorder, the inflammatory bowel disease ulcerative colitis, as examples to facilitate the discussion of how microbial therapy might be rationally designed for specific gastrointestinal diseases. Fecal microbiota transplantation has already shown some efficacy in the treatment of both these disorders; detailed comparisons of studies evaluating commensal and probiotic organisms in the context of these disparate gastrointestinal diseases may shed light on potential protective mechanisms and elucidate how future microbial therapies can be tailored to particular diseases. PMID:27856521

Rational design for the stability improvement of Armillariella tabescens β-mannanase MAN47 based on N-glycosylation modification.

PubMed

Hu, Weixiong; Liu, Xiaoyun; Li, Yufeng; Liu, Daling; Kuang, Zhihe; Qian, Chuiwen; Yao, Dongsheng

2017-02-01

β-Mannanase has been widely used in industries such as food and feed processing and thus has been a target enzyme for biotechnological development. In this study, we sought to improve the stability and protease resistance of a recombinant β-mannanase, MAN47 from Armillariella tabescens, through rationally designed N-glycosylation. Based on homology modeling, molecular docking, secondary structure analysis and glycosylation feasibility analysis, an enhanced aromatic sequon sequence was introduced into specific MAN47 loop regions to facilitate N-glycosylation. The mutant enzymes were expressed in Pichia pastoris SMD1168, and their thermal stability, pH stability, trypsin resistance and pepsin resistance were determined. Two mutant MAN47 enzymes, g-123 and g-347, were glycosylated as expected when expressed in yeast, and their thermal stability, pH stability, and protease resistance were significantly improved compared to the wild-type enzyme. An enzyme with multiple stability characterizations has broad prospects in practical applications, and the rational design N-glycosylation strategy may have applications in simultaneously improving several properties of other biotechnological targets. Copyright © 2016 Elsevier Inc. All rights reserved.

Learning What to Want: Context-Sensitive Preference Learning

PubMed Central

Srivastava, Nisheeth; Schrater, Paul

2015-01-01

We have developed a method for learning relative preferences from histories of choices made, without requiring an intermediate utility computation. Our method infers preferences that are rational in a psychological sense, where agent choices result from Bayesian inference of what to do from observable inputs. We further characterize conditions on choice histories wherein it is appropriate for modelers to describe relative preferences using ordinal utilities, and illustrate the importance of the influence of choice history by explaining all major categories of context effects using them. Our proposal clarifies the relationship between economic and psychological definitions of rationality and rationalizes several behaviors heretofore judged irrational by behavioral economists. PMID:26496645

Rational-operator-based depth-from-defocus approach to scene reconstruction.

PubMed

Li, Ang; Staunton, Richard; Tjahjadi, Tardi

2013-09-01

This paper presents a rational-operator-based approach to depth from defocus (DfD) for the reconstruction of three-dimensional scenes from two-dimensional images, which enables fast DfD computation that is independent of scene textures. Two variants of the approach, one using the Gaussian rational operators (ROs) that are based on the Gaussian point spread function (PSF) and the second based on the generalized Gaussian PSF, are considered. A novel DfD correction method is also presented to further improve the performance of the approach. Experimental results are considered for real scenes and show that both approaches outperform existing RO-based methods.

APPLICATION OF STEEL PIPE PILE LOADING TESTS TO DESIGN VERIFICATION OF FOUNDATION OF THE TOKYO GATE BRIDGE

NASA Astrophysics Data System (ADS)

Saitou, Yutaka; Kikuchi, Yoshiaki; Kusakabe, Osamu; Kiyomiya, Osamu; Yoneyama, Haruo; Kawakami, Taiji

Steel sheet pipe pile foundations with large diameter steel pipe sheet pile were used for the foundation of the main pier of the Tokyo Gateway bridge. However, as for the large diameter steel pipe pile, the bearing mechanism including a pile tip plugging effect is still unclear due to lack of the practical examinations even though loading tests are performed on Trans-Tokyo Bay Highway. In the light of the foregoing problems, static pile loading tests both vertical and horizontal directions, a dynamic loading test, and cone penetration tests we re conducted for determining proper design parameters of the ground for the foundations. Design parameters were determined rationally based on the tests results. Rational design verification was obtained from this research.

Rational Design of Thermally Stable Novel Biocatalytic Nanomaterials: Enzyme Stability in Restricted Spatial Dimensions

NASA Astrophysics Data System (ADS)

Mudhivarthi, Vamsi K.

Enzyme stability is of intense interest in bio-materials science as biocatalysts, and as sensing platforms. This is essentially because the unique properties of DNA, RNA, PAA can be coupled with the interesting and novel properties of proteins to produce systems with unprecedented control over their properties. In this article, the very first examples of enzyme/NA/inorganic hybrid nanomaterials and enzyme-Polyacrylic acid conjugates will be presented. The basic principles of design, synthesis and control of properties of these hybrid materials will be presented first, and this will be followed by a discussion of selected examples from our recent research findings. Data show that key properties of biological catalysts are improved by the inorganic framework especially when the catalyst is co-embedded with DNA. Several examples of such studies with various enzymes and proteins, including horseradish peroxidase (HRP), glucose oxidase (GO), cytochrome c (Cyt c), met-hemoglobin (Hb) and met-myoglobin (Mb) will be discussed. Additionally, key insights obtained by the standard methods of materials science including XRD, SEM and TEM as well as biochemical, calorimetric and spectroscopic methods will be discussed. Furthermore, improved structure and enhanced activities of the biocatalysts in specific cases will be demonstrated along with the potential stabilization mechanisms. Our hypothesis is that nucleic acids provide an excellent control over the enzyme-solid interactions as well as rational assembly of nanomaterials. These novel nanobiohybrid materials may aid in engineering more effective synthetic materials for gene-delivery, RNA-delivery and drug delivery applications.

Sensitivity analysis and approximation methods for general eigenvalue problems

NASA Technical Reports Server (NTRS)

Murthy, D. V.; Haftka, R. T.

1986-01-01

Optimization of dynamic systems involving complex non-hermitian matrices is often computationally expensive. Major contributors to the computational expense are the sensitivity analysis and reanalysis of a modified design. The present work seeks to alleviate this computational burden by identifying efficient sensitivity analysis and approximate reanalysis methods. For the algebraic eigenvalue problem involving non-hermitian matrices, algorithms for sensitivity analysis and approximate reanalysis are classified, compared and evaluated for efficiency and accuracy. Proper eigenvector normalization is discussed. An improved method for calculating derivatives of eigenvectors is proposed based on a more rational normalization condition and taking advantage of matrix sparsity. Important numerical aspects of this method are also discussed. To alleviate the problem of reanalysis, various approximation methods for eigenvalues are proposed and evaluated. Linear and quadratic approximations are based directly on the Taylor series. Several approximation methods are developed based on the generalized Rayleigh quotient for the eigenvalue problem. Approximation methods based on trace theorem give high accuracy without needing any derivatives. Operation counts for the computation of the approximations are given. General recommendations are made for the selection of appropriate approximation technique as a function of the matrix size, number of design variables, number of eigenvalues of interest and the number of design points at which approximation is sought.

Understanding significant processes during work environment interventions to alleviate time pressure and associated sick leave of home care workers--a case study.

PubMed

Andersen, Gunn Robstad; Westgaard, Rolf H

2013-11-15

Ergonomic and work stress interventions rarely show long-term positive effect. The municipality participating in this study received orders from the Norwegian Labour Inspectorate due to an identified unhealthy level of time pressure, and responded by effectuating several work environment interventions. The study aim is to identify critical factors in the interaction between work environment interventions and independent rationalization measures in order to understand a potential negative interfering effect from concurrent rationalizations on a comprehensive work environment intervention. The study, using a historic prospective mixed-method design, comprised 6 home care units in a municipality in Norway (138 respondents, response rate 76.2%; 17 informants). The study included quantitative estimations, register data of sick leave, a time line of significant events and changes, and qualitative descriptions of employee appraisals of their work situation gathered through semi-structured interviews and open survey responses. The work environment interventions were in general regarded as positive by the home care workers. However, all units were simultaneously subjected to substantial contextual instability, involving new work programs, new technology, restructurings, unit mergers, and management replacements, perceived by the home care workers to be major sources of stress. Findings suggest that concurrent changes induced through rationalization resulted in negative exposure effects that negated positive work environment intervention effects, causing an overall deteriorated work situation for the home care workers. Establishment and active utilization of communication channels from workers to managers are recommended in order to increase awareness of putative harmful and interruptive effects of rationalization measures.

Rational pharmacotherapy training for fourth-year medical students.

PubMed

Gelal, Ayse; Gumustekin, Mukaddes; Arici, M Aylin; Gidener, Sedef

2013-01-01

In this study we aimed to evaluate the impact of Rational Pharmacotherapy (RPT) course program, reinforced by video footages, on the rational pharmacotherapy skills of the students. RPT course program has been conducted in Dokuz Eylul University School of Medicine since 2008/9. The course has been organised in accordance with World Health Organisation (WHO) Good Prescribing Guide. The aim of the course was to improve the problem solving skills (methodology for selection of the (p)ersonel-drug, prescription writing and informing patient about his illness and drugs) and communication skills of students. The impact of the course has been measured by pre/post-test design by an objective structured clinical examination (OSCE). In academic year 2010/11, to further improve OSCE score of the students we added doctor-patient communication video footages to the RPT course programme. During training, the students were asked to evaluate the doctor-patient communication and prescription on two video footages using a checklist followed by group discussions. Total post-test OSCE score was significantly higher for 2010/11 academic year students (n = 147) than it was for 2009/10 year students (n = 131). The 2010/11 academic year students performed significantly better than the 2009/10 academic year students on four steps of OSCE. These steps were "defining the patient's problem", "specifying the therapeutic objective", "specifying the non-pharmacological treatment" and "choosing a (drug) treatment, taking all relevant patient characteristics into account". The present study demonstrated that the implementation of video footages and group discussions to WHO/Good Prescribing Method improved the fourth-year medical students' performance in rational pharmacotherapy skills.

A general strategy toward the rational synthesis of metal tungstate nanostructures using plasma electrolytic oxidation method

NASA Astrophysics Data System (ADS)

Jiang, Yanan; Liu, Baodan; Zhai, Zhaofeng; Liu, Xiaoyuan; Yang, Bing; Liu, Lusheng; Jiang, Xin

2015-11-01

A new method based on conventional plasma electrolytic oxidation (PEO) technology has been developed for the rational synthesis of metal tungstate nanostructures. Using this method, ZnWO4 and NiWO4 nanostructures with controllable morphologies (nanorods, nanosheets and microsheets) and superior crystallinity have been synthesized. It has been found that the morphology diversity of ZnWO4 nanostructures can be selectively tailored through tuning the electrolyte concentration and annealing temperatures, showing obvious advantages in comparison to traditional hydrothermal and sol-gel methods. Precise microscopy analyses on the cross section of the PEO coating and ZnWO4 nanostructures confirmed that the precursors initially precipitated in the PEO coating and its surface during plasma discharge process are responsible for the nucleation and subsequent growth of metal tungstate nanostructures by thermal annealing. The method developed in this work represents a general strategy toward the rational synthesis of metal oxide nanostructures and the formation mechanism of metal tungstate nanostructures fabricated by the PEO method is finally discussed.

The Binary Representation of Rational Numbers.

ERIC Educational Resources Information Center

Schmalz, Rosemary

1987-01-01

Presented are the mathematical explanation of the algorithm for representing rational numbers in base two, paper-and-pencil methods for producing the representation, some patterns in these representations, and pseudocode for computer programs to explore these patterns. (MNS)

A rapid and rational approach to generating isomorphous heavy-atom phasing derivatives.

PubMed

Lu, Jinghua; Sun, Peter D

2014-09-01

In attempts to replace the conventional trial-and-error heavy-atom derivative search method with a rational approach, we previously defined heavy metal compound reactivity against peptide ligands. Here, we assembled a composite pH- and buffer-dependent peptide reactivity profile for each heavy metal compound to guide rational heavy-atom derivative search. When knowledge of the best-reacting heavy-atom compound is combined with mass spectrometry assisted derivatization, and with a quick-soak method to optimize phasing, it is likely that the traditional heavy-atom compounds could meet the demand of modern high-throughput X-ray crystallography. As an example, we applied this rational heavy-atom phasing approach to determine a previously unknown mouse serum amyloid A2 crystal structure. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Epileptic seizure classification of EEG time-series using rational discrete short-time fourier transform.

PubMed

Samiee, Kaveh; Kovács, Petér; Gabbouj, Moncef

2015-02-01

A system for epileptic seizure detection in electroencephalography (EEG) is described in this paper. One of the challenges is to distinguish rhythmic discharges from nonstationary patterns occurring during seizures. The proposed approach is based on an adaptive and localized time-frequency representation of EEG signals by means of rational functions. The corresponding rational discrete short-time Fourier transform (DSTFT) is a novel feature extraction technique for epileptic EEG data. A multilayer perceptron classifier is fed by the coefficients of the rational DSTFT in order to separate seizure epochs from seizure-free epochs. The effectiveness of the proposed method is compared with several state-of-art feature extraction algorithms used in offline epileptic seizure detection. The results of the comparative evaluations show that the proposed method outperforms competing techniques in terms of classification accuracy. In addition, it provides a compact representation of EEG time-series.

How clinical rationing works in practice: A case study of morbid obesity surgery.

PubMed

Owen-Smith, Amanda; Donovan, Jenny; Coast, Joanna

2015-12-01

Difficulties in setting healthcare priorities are encountered throughout the world. There is no agreement on the most appropriate principles or methods for healthcare rationing although there is some consensus that it should be undertaken as systematically and accountably as possible. Although some steps towards achieving accountability have been made at the macro and meso level, at the consultation level rationing remains implicit and poorly understood. Using morbid obesity surgery as a case study, we observed a series of UK National Health Service consultations where rationing was ongoing and conducted in-depth interviews with doctors and patients (2011-2014). A longitudinal approach was taken to research and in total 22 consultations were observed and 78 interviews were undertaken. Sampling was undertaken purposively and theoretically and analyses were undertaken thematically. Clinicians needed to prioritise 55 patients from 450 eligible referrals, but disagreed over the extent to which clinical and financial factors were the driving force behind decision-making. The most prominent rationing technique observed in consultations was rationing by selection, but examples of rationing by delay, by deterrence, and by deflection were also commonplace. Although all clinicians sought to avoid rationing by denial, only six of the 22 patients recruited to the research were known to have been treated at the end of the three-year period. Most clinicians sought to manage rationing implicitly, and only one explained the link between decision-making criteria and financial constraints on care availability. Although existing frameworks for categorising NHS rationing techniques were useful in identifying implicit strategies, in practice these techniques over-lapped substantially and we have proposed a simpler framework for analysing NHS rationing decisions at the consultation level, which includes just three categories - rationing by exclusion, rationing by deterrence, and rationing by delay. Copyright © 2015. Published by Elsevier Ltd.

Validation of a pair of computer codes for estimation and optimization of subsonic aerodynamic performance of simple hinged-flap systems for thin swept wings

NASA Technical Reports Server (NTRS)

Carlson, Harry W.; Darden, Christine M.

1988-01-01

Extensive correlations of computer code results with experimental data are employed to illustrate the use of linearized theory attached flow methods for the estimation and optimization of the aerodynamic performance of simple hinged flap systems. Use of attached flow methods is based on the premise that high levels of aerodynamic efficiency require a flow that is as nearly attached as circumstances permit. A variety of swept wing configurations are considered ranging from fighters to supersonic transports, all with leading- and trailing-edge flaps for enhancement of subsonic aerodynamic efficiency. The results indicate that linearized theory attached flow computer code methods provide a rational basis for the estimation and optimization of flap system aerodynamic performance at subsonic speeds. The analysis also indicates that vortex flap design is not an opposing approach but is closely related to attached flow design concepts. The successful vortex flap design actually suppresses the formation of detached vortices to produce a small vortex which is restricted almost entirely to the leading edge flap itself.

Diketopyrrolopyrrole-based carbon dots for photodynamic therapy.

PubMed

He, Haozhe; Zheng, Xiaohua; Liu, Shi; Zheng, Min; Xie, Zhigang; Wang, Yong; Yu, Meng; Shuai, Xintao

2018-06-01

The development of a simple and straightforward strategy to synthesize multifunctional carbon dots for photodynamic therapy (PDT) has been an emerging focus. In this work, diketopyrrolopyrrole-based fluorescent carbon dots (DPP CDs) were designed and synthesized through a facile one-pot hydrothermal method by using diketopyrrolopyrrole (DPP) and chitosan (CTS) as raw materials. DPP CDs not only maintained the ability of DPP to generate singlet oxygen (1O2) but also have excellent hydrophilic properties and outstanding biocompatibility. In vitro and in vivo experiments demonstrated that DPP CDs greatly inhibited the growth of tumor cells under laser irradiation (540 nm). This study highlights the potential of the rational design of CDs for efficient cancer therapy.

Combined loading criterial influence on structural performance

NASA Technical Reports Server (NTRS)

Kuchta, B. J.; Sealey, D. M.; Howell, L. J.

1972-01-01

An investigation was conducted to determine the influence of combined loading criteria on the space shuttle structural performance. The study consisted of four primary phases: Phase (1) The determination of the sensitivity of structural weight to various loading parameters associated with the space shuttle. Phase (2) The determination of the sensitivity of structural weight to various levels of loading parameter variability and probability. Phase (3) The determination of shuttle mission loading parameters variability and probability as a function of design evolution and the identification of those loading parameters where inadequate data exists. Phase (4) The determination of rational methods of combining both deterministic time varying and probabilistic loading parameters to provide realistic design criteria. The study results are presented.

Spacewire router IP-core with priority adaptive routing

NASA Astrophysics Data System (ADS)

Shakhmatov, A. V.; Chekmarev, S. A.; Vergasov, M. Y.; Khanov, V. Kh

2015-10-01

Design of modern spacecraft focuses on using network principles of interaction on-board equipment, in particular in network SpaceWire. Routers are an integral part of most SpaceWire networks. The paper presents an adaptive routing algorithm with a prioritization, allowing more flexibility to manage the routing process. This algorithm is designed to transmit SpaceWire packets over a redundant network. Also a method is proposed for rapid restoration of working capacity after power by saving the routing table and the router configuration in an external non-volatile memory. The proposed solutions used to create IP-core router, and then tested in the FPGA device. The results illustrate the realizability and rationality of the proposed solutions.

The evaluation model of the design of toll

NASA Astrophysics Data System (ADS)

Feng, Shuting

2018-04-01

In recent years, the dramatic increase in traffic burden has highlighted the necessity of rational allocation of toll plaza. At the same time, the need to consider a lot of factors has enhanced the design requirements. In this background, we carry out research on this subject. We propose a reasonable assumption, and abstract the toll plaza into a model only related to B and L. By using the queuing theory and traffic flow theory, we define the throughput, cost and accident prevent with B and L to acquire the base model. By using the method of linear weighting in economics to calculate this model, the optimal B and L strategies are obtained.

Self-assembly into soft materials of molecules derived from naturallyoccurring fatty-acids

NASA Astrophysics Data System (ADS)

Zhang, Mohan

The self-assembly of molecular gelators has provided an attractive route for the construction of nanostructured materials with desired functionalities. A well-defined paradigm for the design of molecular gels is needed, but none has yet been established. One of the important challenges to defining this paradigm is the creation of structure-property correlations for gelators at different distance scales. This dissertation centers on gaining additional insights in the relationship between small changes in gelator structures derived from long-chain, naturally-occurring fatty acids and the properties of the corresponding gels. This approach offers a reasonable method to probe the rational design of molecular gelators. (Abstract shortened by ProQuest.).

Anticancer drug discovery and pharmaceutical chemistry: a history.

PubMed

Braña, Miguel F; Sánchez-Migallón, Ana

2006-10-01

There are several procedures for the chemical discovery and design of new drugs from the point of view of the pharmaceutical or medicinal chemistry. They range from classical methods to the very new ones, such as molecular modeling or high throughput screening. In this review, we will consider some historical approaches based on the screening of natural products, the chances for luck, the systematic screening of new chemical entities and serendipity. Another group comprises rational design, as in the case of metabolic pathways, conformation versus configuration and, finally, a brief description on available new targets to be carried out. In each approach, the structure of some examples of clinical interest will be shown.

13C metabolic flux analysis: optimal design of isotopic labeling experiments.

PubMed

Antoniewicz, Maciek R

2013-12-01

Measuring fluxes by 13C metabolic flux analysis (13C-MFA) has become a key activity in chemical and pharmaceutical biotechnology. Optimal design of isotopic labeling experiments is of central importance to 13C-MFA as it determines the precision with which fluxes can be estimated. Traditional methods for selecting isotopic tracers and labeling measurements did not fully utilize the power of 13C-MFA. Recently, new approaches were developed for optimal design of isotopic labeling experiments based on parallel labeling experiments and algorithms for rational selection of tracers. In addition, advanced isotopic labeling measurements were developed based on tandem mass spectrometry. Combined, these approaches can dramatically improve the quality of 13C-MFA results with important applications in metabolic engineering and biotechnology. Copyright © 2013 Elsevier Ltd. All rights reserved.

Expert system for generating initial layouts of zoom systems with multiple moving lens groups

NASA Astrophysics Data System (ADS)

Cheng, Xuemin; Wang, Yongtian; Hao, Qun; Sasián, José M.

2005-01-01

An expert system is developed for the automatic generation of initial layouts for the design of zoom systems with multiple moving lens groups. The Gaussian parameters of the zoom system are optimized using the damped-least-squares method to achieve smooth zoom cam curves, with the f-number of each lens group in the zoom system constrained to a rational value. Then each lens group is selected automatically from a database according to its range of f-number, field of view, and magnification ratio as it is used in the zoom system. The lens group database is established from the results of analyzing thousands of zoom lens patents. Design examples are given, which show that the scheme is a practical approach to generate starting points for zoom lens design.

Regret and rationalization among smokers in Thailand and Malaysia: findings from the International Tobacco Control Southeast Asia Survey.

PubMed

Lee, Wonkyong B; Fong, Geoffrey T; Zanna, Mark P; Omar, Maizurah; Sirirassamee, Buppha; Borland, Ron

2009-07-01

To test whether differences of history and strength in tobacco control policies will influence social norms, which, in turn, will influence quit intentions, by influencing smokers' regret and rationalization. The data were from the International Tobacco Control (ITC) Policy Evaluation Southeast Asia Survey, a cohort survey of representative samples of adult smokers in Thailand (N = 2,000) and Malaysia (N = 2,006). The survey used a stratified multistage sampling design. Measures included regret, rationalization, social norms, and quit intention. Thai smokers were more likely to have quit intentions than Malaysian smokers. This difference in quit intentions was, in part, explained by the country differences in social norms, regret, and rationalization. Reflecting Thailand's history of stronger tobacco control policies, Thai smokers, compared with Malaysian smokers, perceived more negative social norms toward smoking, were more likely to regret, and less likely to rationalize smoking. Mediational analyses revealed that these differences in social norms, accounted, in part, for the country-quit intention relation and that regret and rationalization accounted, in part, for the social norm-quit intention relation. The results suggest that social norms toward smoking, which are shaped by tobacco control policies, and smokers' regret and rationalization influence quit intentions.

Oligoalanine helical callipers for cell penetration.

PubMed

Pazo, Marta; Juanes, Marisa; Lostalé-Seijo, Irene; Montenegro, Javier

2018-06-04

Even for short peptides that are enriched in basic amino acids, the large chemical space that can be spanned by combinations of natural amino acids hinders the rational design of cell penetrating peptides. We here report on short oligoalanine scaffolds for the fine-tuning of peptide helicity in different media and the study of cell penetrating properties. This strategy allowed the extraction of the structure/activity features required for maximal membrane interaction and cellular penetration at minimal toxicity. These results confirmed oligoalanine helical callipers as optimal scaffolds for the rational design and the identification of cell penetrating peptides.

Experiential versus rational training: a comparison of student attitudes toward homosexuality.

PubMed

Guth, Lorraine J; Lopez, David F; Rojas, Julio; Clements, Kimberly D; Tyler, J Michael

2004-01-01

Based on Epstein's (1994a) cognitive-experiential self-theory, two new training interventions were designed to teach students about gay, lesbian and bisexual issues. The efficacy of these theoretically based interventions was assessed in a short-term (7-week, three occasion) longitudinal study. Fifty undergraduate psychology students were randomly assigned to one of three treatment groups: Rational Training, Experiential Training, or Control Group. A residualized change score procedure was used to analyze change in levels of sexual prejudice and affect across the three types of measurement (pre-test, post-test, and follow-up). A 3 (Rational Training, Experiential Training, Control Group) x 2 (Low Sexual Prejudice, High Sexual Prejudice) MANOVA revealed that after the training, participants in the Experiential Group (affective training) had more accepting attitudes toward homosexuality compared to the Control Group. In addition, participants in the Experiential Group experienced more positive affect compared to the Rational and Control Groups and experienced more negative affect compared to the Rational Group. Findings are discussed and suggestions for future research are provided.

High-throughput identification and rational design of synergistic small-molecule pairs for combating and bypassing antibiotic resistance.

PubMed

Wambaugh, Morgan A; Shakya, Viplendra P S; Lewis, Adam J; Mulvey, Matthew A; Brown, Jessica C S

2017-06-01

Antibiotic-resistant infections kill approximately 23,000 people and cost $20,000,000,000 each year in the United States alone despite the widespread use of small-molecule antimicrobial combination therapy. Antibiotic combinations typically have an additive effect: the efficacy of the combination matches the sum of the efficacies of each antibiotic when used alone. Small molecules can also act synergistically when the efficacy of the combination is greater than the additive efficacy. However, synergistic combinations are rare and have been historically difficult to identify. High-throughput identification of synergistic pairs is limited by the scale of potential combinations: a modest collection of 1,000 small molecules involves 1 million pairwise combinations. Here, we describe a high-throughput method for rapid identification of synergistic small-molecule pairs, the overlap2 method (O2M). O2M extracts patterns from chemical-genetic datasets, which are created when a collection of mutants is grown in the presence of hundreds of different small molecules, producing a precise set of phenotypes induced by each small molecule across the mutant set. The identification of mutants that show the same phenotype when treated with known synergistic molecules allows us to pinpoint additional molecule combinations that also act synergistically. As a proof of concept, we focus on combinations with the antibiotics trimethoprim and sulfamethizole, which had been standard treatment against urinary tract infections until widespread resistance decreased efficacy. Using O2M, we screened a library of 2,000 small molecules and identified several that synergize with the antibiotic trimethoprim and/or sulfamethizole. The most potent of these synergistic interactions is with the antiviral drug azidothymidine (AZT). We then demonstrate that understanding the molecular mechanism underlying small-molecule synergistic interactions allows the rational design of additional combinations that bypass drug resistance. Trimethoprim and sulfamethizole are both folate biosynthesis inhibitors. We find that this activity disrupts nucleotide homeostasis, which blocks DNA replication in the presence of AZT. Building on these data, we show that other small molecules that disrupt nucleotide homeostasis through other mechanisms (hydroxyurea and floxuridine) also act synergistically with AZT. These novel combinations inhibit the growth and virulence of trimethoprim-resistant clinical Escherichia coli and Klebsiella pneumoniae isolates, suggesting that they may be able to be rapidly advanced into clinical use. In sum, we present a generalizable method to screen for novel synergistic combinations, to identify particular mechanisms resulting in synergy, and to use the mechanistic knowledge to rationally design new combinations that bypass drug resistance.

Effect of intravenous drug administration mode on drug distribution in a tumor slab: a finite Fourier transform analysis.

PubMed

Subramaniam, B; Claudius, J S

1990-03-08

Cancer therapy using chemotherapeutic drugs frequently involves injection of the drug into the body through some intravenous mode of administration, viz, continuous (drip) infusion or single/multiple bolus injection(s). An understanding of the effect of the various modes of administration upon tumor penetration of drug is essential to rational design of drug therapy. This paper investigates drug penetration into a model tumor of slab geometry (between two capillaries) in which the overall transport rate of drug is limited by intra-tumor transport characterized by an effective diffusion coefficient. Employing the method of Finite Fourier Transforms (FFT), analytical solutions have been obtained for transient drug distribution in both the plasma and the tumor following three modes of administration, viz, continuous infusion, single bolus injection and equally-spaced equal-dose multiple bolus injections, of a given amount of drug. The qualitative trends exhibited by the plasma drug distribution profiles are consistent with reported experimental studies. Two concepts, viz, the dimensionless decay constant and the plasma/tumor drug concentration trajectories, are found to be particularly useful in the rational design of drug therapy. The dimensionless decay constant provides a measure of the rate of drug decay in the plasma relative to the rate of drug diffusion into the tumor and is thus characteristic of the tumor/drug system. The magnitude of this parameter dictates the choice of drug administration mode for minimizing drug decay in the plasma while simultaneously maximizing drug transport into the tumor. The concentration trajectories provide a measure of the plasma drug concentration relative to the tumor drug concentration at various times following injection. When the tumor drug concentration exceeds the plasma drug concentration, the drug will begin to diffuse out of the tumor. Knowledge of the time at which this diffusion reversal occurs is especially useful for optimum scheduling of subsequent bolus injections in a multiple bolus dosing regimen. There are no reported applications of the FFT method to solve repeated input functions in either the chemical engineering or pharmaceutical science literature. Thus, the application of FFT method to solve multiple bolus injections is a unique one. Use of this FFT based analysis as a predictor tool can limit the number of costly experiments which are being done now to achieve this purpose. Even though the model in its present form is simplified, the analysis thereof has nevertheless led to a better understanding of the various factors that must be taken into account for rational design of drug therapy.

High-throughput identification and rational design of synergistic small-molecule pairs for combating and bypassing antibiotic resistance

PubMed Central

Lewis, Adam J.; Mulvey, Matthew A.

2017-01-01

Antibiotic-resistant infections kill approximately 23,000 people and cost $20,000,000,000 each year in the United States alone despite the widespread use of small-molecule antimicrobial combination therapy. Antibiotic combinations typically have an additive effect: the efficacy of the combination matches the sum of the efficacies of each antibiotic when used alone. Small molecules can also act synergistically when the efficacy of the combination is greater than the additive efficacy. However, synergistic combinations are rare and have been historically difficult to identify. High-throughput identification of synergistic pairs is limited by the scale of potential combinations: a modest collection of 1,000 small molecules involves 1 million pairwise combinations. Here, we describe a high-throughput method for rapid identification of synergistic small-molecule pairs, the overlap2 method (O2M). O2M extracts patterns from chemical-genetic datasets, which are created when a collection of mutants is grown in the presence of hundreds of different small molecules, producing a precise set of phenotypes induced by each small molecule across the mutant set. The identification of mutants that show the same phenotype when treated with known synergistic molecules allows us to pinpoint additional molecule combinations that also act synergistically. As a proof of concept, we focus on combinations with the antibiotics trimethoprim and sulfamethizole, which had been standard treatment against urinary tract infections until widespread resistance decreased efficacy. Using O2M, we screened a library of 2,000 small molecules and identified several that synergize with the antibiotic trimethoprim and/or sulfamethizole. The most potent of these synergistic interactions is with the antiviral drug azidothymidine (AZT). We then demonstrate that understanding the molecular mechanism underlying small-molecule synergistic interactions allows the rational design of additional combinations that bypass drug resistance. Trimethoprim and sulfamethizole are both folate biosynthesis inhibitors. We find that this activity disrupts nucleotide homeostasis, which blocks DNA replication in the presence of AZT. Building on these data, we show that other small molecules that disrupt nucleotide homeostasis through other mechanisms (hydroxyurea and floxuridine) also act synergistically with AZT. These novel combinations inhibit the growth and virulence of trimethoprim-resistant clinical Escherichia coli and Klebsiella pneumoniae isolates, suggesting that they may be able to be rapidly advanced into clinical use. In sum, we present a generalizable method to screen for novel synergistic combinations, to identify particular mechanisms resulting in synergy, and to use the mechanistic knowledge to rationally design new combinations that bypass drug resistance. PMID:28632788

Linking patient satisfaction with nursing care: the case of care rationing - a correlational study.

PubMed

Papastavrou, Evridiki; Andreou, Panayiota; Tsangari, Haritini; Merkouris, Anastasios

2014-01-01

Implicit rationing of nursing care is the withholding of or failure to carry out all necessary nursing measures due to lack of resources. There is evidence supporting a link between rationing of nursing care, nurses' perceptions of their professional environment, negative patient outcomes, and placing patient safety at risk. The aims of the study were: a) To explore whether patient satisfaction is linked to nurse-reported rationing of nursing care and to nurses' perceptions of their practice environment while adjusting for patient and nurse characteristics. b) To identify the threshold score of rationing by comparing the level of patient satisfaction factors across rationing levels. A descriptive, correlational design was employed. Participants in this study included 352 patients and 318 nurses from ten medical and surgical units of five general hospitals. Three measurement instruments were used: the BERNCA scale for rationing of care, the RPPE scale to explore nurses' perceptions of their work environment and the Patient Satisfaction scale to assess the level of patient satisfaction with nursing care. The statistical analysis included the use of Kendall's correlation coefficient to explore a possible relationship between the variables and multiple regression analysis to assess the effects of implicit rationing of nursing care together with organizational characteristics on patient satisfaction. The mean score of implicit rationing of nursing care was 0.83 (SD = 0.52, range = 0-3), the overall mean of RPPE was 2.76 (SD = 0.32, range = 1.28 - 3.69) and the two scales were significantly correlated (τ = -0.234, p < 0.001). The regression analysis showed that care rationing and work environment were related to patient satisfaction, even after controlling for nurse and patient characteristics. The results from the adjusted regression models showed that even at the lowest level of rationing (i.e. 0.5) patients indicated low satisfaction. The results support the relationships between organizational and environmental variables, care rationing and patient satisfaction. The identification of thresholds at which rationing starts to influence patient outcomes in a negative way may allow nurse managers to introduce interventions so as to keep rationing at a level at which patient safety is not jeopardized.

Study on the method to test large-aperture hyperboloid convex mirror

NASA Astrophysics Data System (ADS)

Meng, Xiaohui; Dong, Huiwen; Guo, Wen; Wang, Huijun

2014-08-01

There are numerous reflecting optical system designs that call for large-aperture convex surfaces, such as secondary mirror in on-axis three mirror anastigmatic (TMA). Several methods to test high accuracy hyperboloid convex surfaces are introduced separately in this paper. A kind of arrangement is chosen to test a surface with diameter of 420mm, radius of 1371mm, and conic K -2.1229. The CGH compensator for testing is designed, which is made up of illumination lens and hologram test plate with designed residual wavefront aberration less than 0.001λ (RMS). The second transmitted method that is equipped with a technical flat surface coating by Ag film in the bottom of surface mirror under test, which form an auto-collimation optical system to eliminate the aberration. The Hindle-Simpson test that requires a larger meniscus lens to compensate the optical aberration, and the designed result of optical test system is less than 0.0016λ. Contrasting the CGH compensator and the second transmitted method, the Hindle-Simpson testing method has the advantage of it is easily to manufacture and adjust; meanwhile the test result is stable and has been less affected by the environment. It has been found that the method is rational and reliable, and it can fulfill the requirement of manufacturing and testing process for hyperboloid convex mirrors.

Pharmacokinetic-Pharmacodynamic Modeling in Pediatric Drug Development, and the Importance of Standardized Scaling of Clearance.

PubMed

Germovsek, Eva; Barker, Charlotte I S; Sharland, Mike; Standing, Joseph F

2018-04-19

Pharmacokinetic/pharmacodynamic (PKPD) modeling is important in the design and conduct of clinical pharmacology research in children. During drug development, PKPD modeling and simulation should underpin rational trial design and facilitate extrapolation to investigate efficacy and safety. The application of PKPD modeling to optimize dosing recommendations and therapeutic drug monitoring is also increasing, and PKPD model-based dose individualization will become a core feature of personalized medicine. Following extensive progress on pediatric PK modeling, a greater emphasis now needs to be placed on PD modeling to understand age-related changes in drug effects. This paper discusses the principles of PKPD modeling in the context of pediatric drug development, summarizing how important PK parameters, such as clearance (CL), are scaled with size and age, and highlights a standardized method for CL scaling in children. One standard scaling method would facilitate comparison of PK parameters across multiple studies, thus increasing the utility of existing PK models and facilitating optimal design of new studies.

Design of cognitive engine for cognitive radio based on the rough sets and radial basis function neural network

NASA Astrophysics Data System (ADS)

Yang, Yanchao; Jiang, Hong; Liu, Congbin; Lan, Zhongli

2013-03-01

Cognitive radio (CR) is an intelligent wireless communication system which can dynamically adjust the parameters to improve system performance depending on the environmental change and quality of service. The core technology for CR is the design of cognitive engine, which introduces reasoning and learning methods in the field of artificial intelligence, to achieve the perception, adaptation and learning capability. Considering the dynamical wireless environment and demands, this paper proposes a design of cognitive engine based on the rough sets (RS) and radial basis function neural network (RBF_NN). The method uses experienced knowledge and environment information processed by RS module to train the RBF_NN, and then the learning model is used to reconfigure communication parameters to allocate resources rationally and improve system performance. After training learning model, the performance is evaluated according to two benchmark functions. The simulation results demonstrate the effectiveness of the model and the proposed cognitive engine can effectively achieve the goal of learning and reconfiguration in cognitive radio.

Toward Rational Design of Cu/SSZ-13 Selective Catalytic Reduction Catalysts: Implications from Atomic-Level Understanding of Hydrothermal Stability

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

Song, James; Wang, Yilin; Walter, Eric D.

The hydrothermal stability of Cu/SSZ-13 SCR catalysts has been extensively studied, yet atomic level understanding of changes to the zeolite support and the Cu active sites during hydrothermal aging are still lacking. In this work, via the utilization of spectroscopic methods including solid-state 27Al and 29Si NMR, EPR, DRIFTS, and XPS, together with imaging and elemental mapping using STEM, detailed kinetic analyses, and theoretical calculations with DFT, various Cu species, including two types of isolated active sites and CuOx clusters, were precisely quantified for samples hydrothermally aged under varying conditions. This quantification convincingly confirms the exceptional hydrothermal stability of isolatedmore » Cu2+-2Z sites, and the gradual conversion of [Cu(OH)]+-Z to CuOx clusters with increasing aging severity. This stability difference is rationalized from the hydrolysis activation barrier difference between the two isolated sites via DFT. Discussions are provided on the nature of the CuOx clusters, and their possible detrimental roles on catalyst stability. Finally, a few rational design principles for Cu/SSZ-13 are derived rigorously from the atomic-level understanding of this catalyst obtained here. The authors gratefully acknowledge the US Department of Energy (DOE), Energy Efficiency and Renewable Energy, Vehicle Technologies Office for the support of this work. Computing time was granted by a user proposal at the William R. Wiley Environmental Molecular Sciences Laboratory (EMSL) and by the National Energy Research Scientific Computing Center (NERSC). The experimental studies described in this paper were performed in the EMSL, a national scientific user facility sponsored by the DOE’s Office of Biological and Environmental Research and located at Pacific Northwest National Laboratory (PNNL). PNNL is operated for the US DOE by Battelle.« less

MIRATE: MIps RATional dEsign Science Gateway.

PubMed

Busato, Mirko; Distefano, Rosario; Bates, Ferdia; Karim, Kal; Bossi, Alessandra Maria; López Vilariño, José Manuel; Piletsky, Sergey; Bombieri, Nicola; Giorgetti, Alejandro

2018-06-13

Molecularly imprinted polymers (MIPs) are high affinity robust synthetic receptors, which can be optimally synthesized and manufactured more economically than their biological equivalents (i.e. antibody). In MIPs production, rational design based on molecular modeling is a commonly employed technique. This mostly aids in (i) virtual screening of functional monomers (FMs), (ii) optimization of monomer-template ratio, and (iii) selectivity analysis. We present MIRATE, an integrated science gateway for the intelligent design of MIPs. By combining and adapting multiple state-of-the-art bioinformatics tools into automated and innovative pipelines, MIRATE guides the user through the entire process of MIPs' design. The platform allows the user to fully customize each stage involved in the MIPs' design, with the main goal to support the synthesis in the wet-laboratory. MIRATE is freely accessible with no login requirement at http://mirate.di.univr.it/. All major browsers are supported.

Rationing critical care medicine: recent studies and current trends.

PubMed

Ward, Nicholas S

2005-12-01

This paper reviews the literature on the rationing of critical care resources. Although much has been written about the concept of rationing, there have been few scientific studies as to its prevalence. A recent meta-analysis reviewed all previously published studies on rationing access to intensive care units but little is known about practices within the intensive care unit. Much literature in the past few years has focused on the growing use of critical care resources and projections for the future. Several authors suggest there may be a crisis in financial or personnel resources if some rationing does not take place. Other papers have argued that the methods of rationing critical care previously proposed, such as limiting the care of dying patients or using cost-effectiveness analysis to determine care, may not be effective or viewed as ethical by some. Finally, several recent papers review how critical care is practiced and allocated in India and Asian countries that already practice open rationing in their health care systems. There is currently no published evidence that overt rationing is taking place in critical care medicine. There is growing evidence that in the future, the need for critical care may outstrip financial resources unless some form of rationing takes place. It is also clear from the literature that choosing how to ration critical care will be a difficult task.

Transitioning Rationally Designed Catalytic Materials to Real 'Working' Catalysts Produced at Commercial Scale: Nanoparticle Materials

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

Schaidle, Joshua A.; Habas, Susan E.; Baddour, Frederick G.

Catalyst design, from idea to commercialization, requires multi-disciplinary scientific and engineering research and development over 10-20 year time periods. Historically, the identification of new or improved catalyst materials has largely been an empirical trial-and-error process. However, advances in computational capabilities (new tools and increased processing power) coupled with new synthetic techniques have started to yield rationally-designed catalysts with controlled nano-structures and tailored properties. This technological advancement represents an opportunity to accelerate the catalyst development timeline and to deliver new materials that outperform existing industrial catalysts or enable new applications, once a number of unique challenges associated with the scale-up ofmore » nano-structured materials are overcome.« less

Nucleic acids for the rational design of reaction circuits.

PubMed

Padirac, Adrien; Fujii, Teruo; Rondelez, Yannick

2013-08-01

Nucleic acid-based circuits are rationally designed in vitro assemblies that can perform complex preencoded programs. They can be used to mimic in silico computations. Recent works emphasized the modularity and robustness of these circuits, which allow their scaling-up. Another new development has led to dynamic, time-responsive systems that can display emergent behaviors like oscillations. These are closely related to biological architectures and provide an in vitro model of in vivo information processing. Nucleic acid circuits have already been used to handle various processes for technological or biotechnological purposes. Future applications of these chemical smart systems will benefit from the rapidly growing ability to design, construct, and model nucleic acid circuits of increasing size. Copyright © 2012 Elsevier Ltd. All rights reserved.

Modern Vaccines/Adjuvants Formulation Session 6: Vaccine &Adjuvant Formulation & Production 15-17 May 2013, Lausanne, Switzerland.

PubMed

Fox, Christopher B

2013-09-01

The Modern Vaccines/Adjuvants Formulation meeting aims to fill a critical gap in current vaccine development efforts by bringing together formulation scientists and immunologists to emphasize the importance of rational formulation design in order to optimize vaccine and adjuvant bioactivity, safety, and manufacturability. Session 6 on Vaccine and Adjuvant Formulation and Production provided three examples of this theme, with speakers emphasizing the need for extensive physicochemical characterization of adjuvant-antigen interactions, the rational formulation design of a CD8+ T cell-inducing adjuvant based on immunological principles, and the development and production of a rabies vaccine by a developing country manufacturer. Throughout the session, the practical importance of sound formulation and manufacturing design accompanied by analytical characterization was highlighted.

Design of a small molecule against an oncogenic noncoding RNA.

PubMed

Velagapudi, Sai Pradeep; Cameron, Michael D; Haga, Christopher L; Rosenberg, Laura H; Lafitte, Marie; Duckett, Derek R; Phinney, Donald G; Disney, Matthew D

2016-05-24

The design of precision, preclinical therapeutics from sequence is difficult, but advances in this area, particularly those focused on rational design, could quickly transform the sequence of disease-causing gene products into lead modalities. Herein, we describe the use of Inforna, a computational approach that enables the rational design of small molecules targeting RNA to quickly provide a potent modulator of oncogenic microRNA-96 (miR-96). We mined the secondary structure of primary microRNA-96 (pri-miR-96) hairpin precursor against a database of RNA motif-small molecule interactions, which identified modules that bound RNA motifs nearby and in the Drosha processing site. Precise linking of these modules together provided Targaprimir-96 (3), which selectively modulates miR-96 production in cancer cells and triggers apoptosis. Importantly, the compound is ineffective on healthy breast cells, and exogenous overexpression of pri-miR-96 reduced compound potency in breast cancer cells. Chemical Cross-Linking and Isolation by Pull-Down (Chem-CLIP), a small-molecule RNA target validation approach, shows that 3 directly engages pri-miR-96 in breast cancer cells. In vivo, 3 has a favorable pharmacokinetic profile and decreases tumor burden in a mouse model of triple-negative breast cancer. Thus, rational design can quickly produce precision, in vivo bioactive lead small molecules against hard-to-treat cancers by targeting oncogenic noncoding RNAs, advancing a disease-to-gene-to-drug paradigm.

The Paradox of "Structured" Methods for Software Requirements Management: A Case Study of an e-Government Development Project

NASA Astrophysics Data System (ADS)

Conboy, Kieran; Lang, Michael

This chapter outlines the alternative perspectives of "rationalism" and "improvisation" within information systems development and describes the major shortcomings of each. It then discusses how these shortcomings manifested themselves within an e-government case study where a "structured" requirements management method was employed. Although this method was very prescriptive and firmly rooted in the "rational" paradigm, it was observed that users often resorted to improvised behaviour, such as privately making decisions on how certain aspects of the method should or should not be implemented.

Analytic Procedures For Designing and Evaluating Decision Aids.

DTIC Science & Technology

1980-04-01

the taxonomy of decision charateristics . Chapter 5 applies the taxonomies to the information processing functions needed for AAW decisions, and...rationality emphasizes the extent to which organizations and other social institutions consist of individuals who pursue individual objectives by means of...adaptive rationality is always wrong or naive; most of us know persons that seem to be naturally good decision-makers. There is no logic that guarantees

Effect of supplementing orchardgrass herbage with a total mixed ration or flaxseed fermentation profile and bacterial protein synthesis in continuous culture

USDA-ARS?s Scientific Manuscript database

A 4-unit dual-flow continuous culture fermentor system was used to evaluate the effects of herbage, a total mixed ration (TMR) and flaxseed on nutrient digestibility and microbial N synthesis. Treatments were randomly assigned to fermentors in a 4 x 4 Latin square design. Each fermentor was fed a to...

A Rational Reconstruction of the Kinetic Molecular Theory of Gases Based on History and Philosophy of Science and Its Implications for Chemistry Textbooks.

ERIC Educational Resources Information Center

Niaz, Mansoor

2000-01-01

Describes a study that was designed to develop a framework for examining the way in which chemistry textbooks describe the kinetic theory and related issues. The framework was developed by a rational reconstruction of the kinetic molecular theory of gases based on historians and philosophers of science. (Contains 102 references.)(Author/LRW)

Rational design of hierarchical ZnO@Carbon nanoflower for high performance lithium ion battery anodes

NASA Astrophysics Data System (ADS)

liu, Huichao; Shi, Ludi; Li, Dongzhi; Yu, Jiali; Zhang, Han-Ming; Ullah, Shahid; Yang, Bo; Li, Cuihua; Zhu, Caizhen; Xu, Jian

2018-05-01

The rational structure design and strong interfacial bonding are crucially desired for high performance zinc oxide (ZnO)/carbon composite electrodes. In this context, micro-nano secondary structure design and strong dopamine coating strategies are adopted for the fabrication of flower-like ZnO/carbon (ZnO@C nanoflowers) composite electrodes. The results show the ZnO@C nanoflowers (2-6 μm) are assembled by hierarchical ZnO nanosheets (∼27 nm) and continuous carbon framework. The micro-nano secondary architecture can facilitate the penetration of electrolyte, shorten lithium ions diffusion length, and hinder the aggregation of the nanosheets. Moreover, the strong chemical interaction between ZnO and coating carbon layer via C-Zn bond improves structure stability as well as the electronic conductivity. As a synergistic result, when evaluated as lithium ion batteries (LIBs) anode, the ZnO@C nanoflower electrodes show high reversible capacity of ca. 1200 mA h g-1 at 0.1 A g-1 after 80 cycles. As well as good long-cycling stability (638 and 420 mA h g-1 at 1 and 5 A g-1 after 500 cycles, respectively) and excellent rate capability. Therefore, this rational design of ZnO@C nanoflowers electrode is a promising anode for high-performance LIBs.

Rational Design Approach for Enhancing Higher-Mode Response of a Microcantilever in Vibro-Impacting Mode.

PubMed

Migliniene, Ieva; Ostasevicius, Vytautas; Gaidys, Rimvydas; Dauksevicius, Rolanas; Janusas, Giedrius; Jurenas, Vytautas; Krasauskas, Povilas

2017-12-12

This paper proposes an approach for designing an efficient vibration energy harvester based on a vibro-impacting piezoelectric microcantilever with a geometric shape that has been rationally modified in accordance with results of dynamic optimization. The design goal is to increase the amplitudes of higher-order vibration modes induced during the vibro-impact response of the piezoelectric transducer, thereby providing a means to improve the energy conversion efficiency and power output. A rational configuration of the energy harvester is proposed and it is demonstrated that the new design retains essential modal characteristics of the optimal microcantilever structures, further providing the added benefit of less costly fabrication. The effects of structural dynamics associated with advantageous exploitation of higher vibration modes are analyzed experimentally by means of laser vibrometry as well as numerically via transient simulations of microcantilever response to random excitation. Electrical characterization results indicate that the proposed harvester outperforms its conventional counterpart (based on the microcantilever of the constant cross-section) in terms of generated electrical output. Reported results may serve for the development of impact-type micropower generators with harvesting performance that is enhanced by virtue of self-excitation of large intensity higher-order mode responses when the piezoelectric transducer is subjected to relatively low-frequency excitation with strongly variable vibration magnitudes.

Starlings uphold principles of economic rationality for delay and probability of reward.

PubMed

Monteiro, Tiago; Vasconcelos, Marco; Kacelnik, Alex

2013-04-07

Rationality principles are the bedrock of normative theories of decision-making in biology and microeconomics, but whereas in microeconomics, consistent choice underlies the notion of utility; in biology, the assumption of consistent selective pressures justifies modelling decision mechanisms as if they were designed to maximize fitness. In either case, violations of consistency contradict expectations and attract theoretical interest. Reported violations of rationality in non-humans include intransitivity (i.e. circular preferences) and lack of independence of irrelevant alternatives (changes in relative preference between options when embedded in different choice sets), but the extent to which these observations truly represent breaches of rationality is debatable. We tested both principles with starlings (Sturnus vulgaris), training subjects either with five options differing in food delay (exp. 1) or with six options differing in reward probability (exp. 2), before letting them choose repeatedly one option out of several binary and trinary sets of options. The starlings conformed to economic rationality on both tests, showing strong stochastic transitivity and no violation of the independence principle. These results endorse the rational choice and optimality approaches used in behavioural ecology, and highlight the need for functional and mechanistic enquiring when apparent violations of such principles are observed.

Starlings uphold principles of economic rationality for delay and probability of reward

PubMed Central

Monteiro, Tiago; Vasconcelos, Marco; Kacelnik, Alex

2013-01-01

Rationality principles are the bedrock of normative theories of decision-making in biology and microeconomics, but whereas in microeconomics, consistent choice underlies the notion of utility; in biology, the assumption of consistent selective pressures justifies modelling decision mechanisms as if they were designed to maximize fitness. In either case, violations of consistency contradict expectations and attract theoretical interest. Reported violations of rationality in non-humans include intransitivity (i.e. circular preferences) and lack of independence of irrelevant alternatives (changes in relative preference between options when embedded in different choice sets), but the extent to which these observations truly represent breaches of rationality is debatable. We tested both principles with starlings (Sturnus vulgaris), training subjects either with five options differing in food delay (exp. 1) or with six options differing in reward probability (exp. 2), before letting them choose repeatedly one option out of several binary and trinary sets of options. The starlings conformed to economic rationality on both tests, showing strong stochastic transitivity and no violation of the independence principle. These results endorse the rational choice and optimality approaches used in behavioural ecology, and highlight the need for functional and mechanistic enquiring when apparent violations of such principles are observed. PMID:23390098

Cognitive success: instrumental justifications of normative systems of reasoning.

PubMed

Schurz, Gerhard

2014-01-01

In the first part of the paper (sec. 1-4), I argue that Elqayam and Evan's (2011) distinction between normative and instrumental conceptions of cognitive rationality corresponds to deontological vs. teleological accounts in meta-ethics. I suggest that Elqayam and Evans' distinction be replaced by the distinction between a-priori intuition-based vs. a-posteriori success-based accounts of cognitive rationality. The value of cognitive success lies in its instrumental rationality for almost-all practical purposes. In the second part (sec. 5-7), I point out that the Elqayam and Evans's distinction between normative and instrumental rationality is coupled with a second distinction: between logically general vs. locally adaptive accounts of rationality. I argue that these are two independent distinctions that should be treated as independent dimensions. I also demonstrate that logically general systems of reasoning can be instrumentally justified. However, such systems can only be cognitively successful if they are paired with successful inductive reasoning, which is the area where the program of adaptive (ecological) rationality emerged, because there are no generally optimal inductive reasoning methods. I argue that the practical necessity of reasoning under changing environments constitutes a dilemma for ecological rationality, which I attempt to solve within a dual account of rationality.

Rational-Emotive Therapy with Children and Adolescents: Treatment Strategies.

ERIC Educational Resources Information Center

Bernard, Michael E.

1990-01-01

Presents rational-emotive therapy (RET) conceptualization of childhood disorders, discussing interaction of child temperament and parenting styles. Discusses RET child treatment goals, which involve modification of negative and inappropriate childhood emotions. Illustrates particular RET cognitive change methods (philosophical disputation;…

Appendix G : end region design models.

DOT National Transportation Integrated Search

2013-03-01

The 2007 AASHTO LRFD Bridge Design Specifications contain prescriptive : requirements for the quantity and placement of confinement reinforcement located in the bottom : flange of pretensioned concrete I-girders. This chapter proposes a rational mode...

Design, Synthesis and Affinity Properties of Biologically Active Peptide and Protein Conjugates of Cotton Cellulose

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

Edwards, J. V.; Goheen, Steven C.

The formation of peptide and protein conjugates of cellulose on cotton fabrics provides promising leads for the development of wound healing, antibacterial, and decontaminating textiles. An approach to the design, synthesis, and analysis of bioconjugates containing cellulose peptide and protein conjugates includes: 1) computer graphic modeling for a rationally designed structure; 2) attachment of the peptide or protein to cotton cellulose through a linker amino acid, and 3) characterization of the resulting bioconjugate. Computer graphic simulation of protein and peptide cellulose conjugates gives a rationally designed biopolymer to target synthetic modifications to the cotton cellulose. Techniques for preparing these typesmore » of conjugates involve both sequential assembly of the peptide on the fabric and direct crosslinking of the peptide or protein as cellulose bound esters or carboxymethylcellulose amides.« less

Supracolloidal fullerene-like cages: design principles and formation mechanisms.

PubMed

Li, Zhan-Wei; Zhu, You-Liang; Lu, Zhong-Yuan; Sun, Zhao-Yan

2016-11-30

How to create novel desired structures by rational design of building blocks represents a significant challenge in materials science. Here we report a conceptually new design principle for creating supracolloidal fullerene-like cages through the self-assembly of soft patchy particles interacting via directional nonbonded interactions by mimicking non-planar sp 2 hybridized carbon atoms in C 60 . Our numerical investigations demonstrate that the rational design of patch configuration, size, and interaction can drive soft three-patch particles to reversibly self-assemble into a vast collection of supracolloidal fullerene-like cages. We further elucidate the formation mechanisms of supracolloidal fullerene-like cages by analyzing the structural characteristics and the formation process. Our results provide conceptual and practical guidance towards the experimental realization of supracolloidal fullerene-like cages, as well as a new perspective on understanding the fullerene formation mechanisms.

An identification method for damping ratio in rotor systems

NASA Astrophysics Data System (ADS)

Wang, Weimin; Li, Qihang; Gao, Jinji; Yao, Jianfei; Allaire, Paul

2016-02-01

Centrifugal compressor testing with magnetic bearing excitations is the last step to assure the compressor rotordynamic stability in the designed operating conditions. To meet the challenges of stability evaluation, a new method combining the rational polynomials method (RPM) with the weighted instrumental variables (WIV) estimator to fit the directional frequency response function (dFRF) is presented. Numerical simulation results show that the method suggested in this paper can identify the damping ratio of the first forward and backward modes with high accuracy, even in a severe noise environment. Experimental tests were conducted to study the effect of different bearing configurations on the stability of rotor. Furthermore, two example centrifugal compressors (a nine-stage straight-through and a six-stage back-to-back) were employed to verify the feasibility of identification method in industrial configurations as well.

An Efficient Computational Model to Predict Protonation at the Amide Nitrogen and Reactivity along the C–N Rotational Pathway

PubMed Central

Szostak, Roman; Aubé, Jeffrey

2015-01-01

N-protonation of amides is critical in numerous biological processes, including amide bonds proteolysis and protein folding, as well as in organic synthesis as a method to activate amide bonds towards unconventional reactivity. A computational model enabling prediction of protonation at the amide bond nitrogen atom along the C–N rotational pathway is reported. Notably, this study provides a blueprint for the rational design and application of amides with a controlled degree of rotation in synthetic chemistry and biology. PMID:25766378

Renormalization group contraction of tensor networks in three dimensions

NASA Astrophysics Data System (ADS)

García-Sáez, Artur; Latorre, José I.

2013-02-01

We present a new strategy for contracting tensor networks in arbitrary geometries. This method is designed to follow as strictly as possible the renormalization group philosophy, by first contracting tensors in an exact way and, then, performing a controlled truncation of the resulting tensor. We benchmark this approximation procedure in two dimensions against an exact contraction. We then apply the same idea to a three-dimensional quantum system. The underlying rational for emphasizing the exact coarse graining renormalization group step prior to truncation is related to monogamy of entanglement.

The appropriate use of technology (particularly in medical problems of the elderly).

PubMed

Gilbert, F I

1990-09-01

Technology, particularly "high" technology, with little solid data, is often blamed for much of our increasing cost of health care. Politics and emotions are poor substitutes for accurate information needed for rational solutions. By targeting the desired outcome and studying the process needed to reach the outcome, we can make better decisions. The methods of designing, conducting and funding the studies needed to answer the difficult questions posed by the use of high technology in the elderly are available. Do we have the wisdom to use them?

PROCESS DESIGN MANUAL: LAND TREATMENT OF MUNICIPAL WASTEWATER

EPA Science Inventory

The manual presents a rational procedure for the design of land treatment systems. Slow rate, rapid infiltration, and overland flow processes for the treatment of municipal wastewaters are discussed in detail, and the design concepts and criteria are presented. A two-phased plann...

Rational selection of structurally diverse natural product scaffolds with favorable ADME properties for drug discovery.

PubMed

Samiulla, D S; Vaidyanathan, V V; Arun, P C; Balan, G; Blaze, M; Bondre, S; Chandrasekhar, G; Gadakh, A; Kumar, R; Kharvi, G; Kim, H O; Kumar, S; Malikayil, J A; Moger, M; Mone, M K; Nagarjuna, P; Ogbu, C; Pendhalkar, D; Rao, A V S Raja; Rao, G Venkateshwar; Sarma, V K; Shaik, S; Sharma, G V R; Singh, S; Sreedhar, C; Sonawane, R; Timmanna, U; Hardy, L W

2005-01-01

Natural product analogs are significant sources for therapeutic agents. To capitalize efficiently on the effective features of naturally occurring substances, a natural product-based library production platform has been devised at Aurigene for drug lead discovery. This approach combines the attractive biological and physicochemical properties of natural product scaffolds, provided by eons of natural selection, with the chemical diversity available from parallel synthetic methods. Virtual property analysis, using computational methods described here, guides the selection of a set of natural product scaffolds that are both structurally diverse and likely to have favorable pharmacokinetic properties. The experimental characterization of several in vitro ADME properties of twenty of these scaffolds, and of a small set of designed congeners based upon one scaffold, is also described. These data confirm that most of the scaffolds and the designed library members have properties favorable to their utilization for creating libraries of lead-like molecules.

Nanostructured electrocatalysts with tunable activity and selectivity

NASA Astrophysics Data System (ADS)

Mistry, Hemma; Varela, Ana Sofia; Kühl, Stefanie; Strasser, Peter; Cuenya, Beatriz Roldan

2016-04-01

The field of electrocatalysis has undergone tremendous advancement in the past few decades, in part owing to improvements in catalyst design at the nanoscale. These developments have been crucial for the realization of and improvement in alternative energy technologies based on electrochemical reactions such as fuel cells. Through the development of novel synthesis methods, characterization techniques and theoretical methods, rationally designed nanoscale electrocatalysts with tunable activity and selectivity have been achieved. This Review explores how nanostructures can be used to control electrochemical reactivity, focusing on three model reactions: O2 electroreduction, CO2 electroreduction and ethanol electrooxidation. The mechanisms behind nanoscale control of reactivity are discussed, such as the presence of low-coordinated sites or facets, strain, ligand effects and bifunctional effects in multimetallic materials. In particular, studies of how particle size, shape and composition in nanostructures can be used to tune reactivity are highlighted.

Ligand-regulated peptides: a general approach for modulating protein-peptide interactions with small molecules.

PubMed

Binkowski, Brock F; Miller, Russell A; Belshaw, Peter J

2005-07-01

We engineered a novel ligand-regulated peptide (LiRP) system where the binding activity of intracellular peptides is controlled by a cell-permeable small molecule. In the absence of ligand, peptides expressed as fusions in an FKBP-peptide-FRB-GST LiRP scaffold protein are free to interact with target proteins. In the presence of the ligand rapamycin, or the nonimmunosuppressive rapamycin derivative AP23102, the scaffold protein undergoes a conformational change that prevents the interaction of the peptide with the target protein. The modular design of the scaffold enables the creation of LiRPs through rational design or selection from combinatorial peptide libraries. Using these methods, we identified LiRPs that interact with three independent targets: retinoblastoma protein, c-Src, and the AMP-activated protein kinase. The LiRP system should provide a general method to temporally and spatially regulate protein function in cells and organisms.

A Science and Risk-Based Pragmatic Methodology for Blend and Content Uniformity Assessment.

PubMed

Sayeed-Desta, Naheed; Pazhayattil, Ajay Babu; Collins, Jordan; Doshi, Chetan

2018-04-01

This paper describes a pragmatic approach that can be applied in assessing powder blend and unit dosage uniformity of solid dose products at Process Design, Process Performance Qualification, and Continued/Ongoing Process Verification stages of the Process Validation lifecycle. The statistically based sampling, testing, and assessment plan was developed due to the withdrawal of the FDA draft guidance for industry "Powder Blends and Finished Dosage Units-Stratified In-Process Dosage Unit Sampling and Assessment." This paper compares the proposed Grouped Area Variance Estimate (GAVE) method with an alternate approach outlining the practicality and statistical rationalization using traditional sampling and analytical methods. The approach is designed to fit solid dose processes assuring high statistical confidence in both powder blend uniformity and dosage unit uniformity during all three stages of the lifecycle complying with ASTM standards as recommended by the US FDA.

Prediction of Surface and pH-Specific Binding of Peptides to Metal and Oxide Nanoparticles

NASA Astrophysics Data System (ADS)

Heinz, Hendrik; Lin, Tzu-Jen; Emami, Fateme Sadat; Ramezani-Dakhel, Hadi; Naik, Rajesh; Knecht, Marc; Perry, Carole C.; Huang, Yu

2015-03-01

The mechanism of specific peptide adsorption onto metallic and oxidic nanostructures has been elucidated in atomic resolution using novel force fields and surface models in comparison to measurements. As an example, variations in peptide adsorption on Pd and Pt nanoparticles depending on shape, size, and location of peptides on specific bounding facets are explained. Accurate computational predictions of reaction rates in C-C coupling reactions using particle models derived from HE-XRD and PDF data illustrate the utility of computational methods for the rational design of new catalysts. On oxidic nanoparticles such as silica and apatites, it is revealed how changes in pH lead to similarity scores of attracted peptides lower than 20%, supported by appropriate model surfaces and data from adsorption isotherms. The results demonstrate how new computational methods can support the design of nanoparticle carriers for drug release and the understanding of calcification mechanisms in the human body.

Deterrence from Cold War to Long War: Lessons from Six Decades of RAND Research

DTIC Science & Technology

2008-01-01

highly credible intention. Declaring an intention to retaliate for an attack on U.S. territory was no threat in Schelling’s formulation ; it was a...unconditional commitments are not rational . We shall say 14 Deterrence—From Cold War to Long War that they represent a non- rational element in...this method is impractical. Another strategy that Schelling discussed was embracing non- rationality and simply giving the impression that U.S

Cameo: A Python Library for Computer Aided Metabolic Engineering and Optimization of Cell Factories.

PubMed

Cardoso, João G R; Jensen, Kristian; Lieven, Christian; Lærke Hansen, Anne Sofie; Galkina, Svetlana; Beber, Moritz; Özdemir, Emre; Herrgård, Markus J; Redestig, Henning; Sonnenschein, Nikolaus

2018-04-20

Computational systems biology methods enable rational design of cell factories on a genome-scale and thus accelerate the engineering of cells for the production of valuable chemicals and proteins. Unfortunately, the majority of these methods' implementations are either not published, rely on proprietary software, or do not provide documented interfaces, which has precluded their mainstream adoption in the field. In this work we present cameo, a platform-independent software that enables in silico design of cell factories and targets both experienced modelers as well as users new to the field. It is written in Python and implements state-of-the-art methods for enumerating and prioritizing knockout, knock-in, overexpression, and down-regulation strategies and combinations thereof. Cameo is an open source software project and is freely available under the Apache License 2.0. A dedicated Web site including documentation, examples, and installation instructions can be found at http://cameo.bio . Users can also give cameo a try at http://try.cameo.bio .

Compiler-aided systematic construction of large-scale DNA strand displacement circuits using unpurified components

NASA Astrophysics Data System (ADS)

Thubagere, Anupama J.; Thachuk, Chris; Berleant, Joseph; Johnson, Robert F.; Ardelean, Diana A.; Cherry, Kevin M.; Qian, Lulu

2017-02-01

Biochemical circuits made of rationally designed DNA molecules are proofs of concept for embedding control within complex molecular environments. They hold promise for transforming the current technologies in chemistry, biology, medicine and material science by introducing programmable and responsive behaviour to diverse molecular systems. As the transformative power of a technology depends on its accessibility, two main challenges are an automated design process and simple experimental procedures. Here we demonstrate the use of circuit design software, combined with the use of unpurified strands and simplified experimental procedures, for creating a complex DNA strand displacement circuit that consists of 78 distinct species. We develop a systematic procedure for overcoming the challenges involved in using unpurified DNA strands. We also develop a model that takes synthesis errors into consideration and semi-quantitatively reproduces the experimental data. Our methods now enable even novice researchers to successfully design and construct complex DNA strand displacement circuits.

Effects of antibody, drug and linker on the preclinical and clinical toxicities of antibody-drug conjugates

PubMed Central

Donaghy, Heather

2016-01-01

ABSTRACT Antibody-drug conjugates (ADCs) represent a new class of cancer therapeutics. Their design involves a tumor-specific antibody, a linker and a cytotoxic payload. They were designed to allow specific targeting of highly potent cytotoxic agents to tumor cells whilst sparing normal cells. Frequent toxicities that may be driven by any of the components of an ADC have been reported. There are currently more than 50 ADCs in active clinical development, and a further ∼20 that have been discontinued. For this review, the reported toxicities of ADCs were analysed, and the mechanisms for their effects are explored in detail. Methods to reduce toxicities, including dosing strategies and drug design, are discussed. The toxicities reported for active and discontinued drugs are important to drive the rational design and improve the therapeutic index of ADCs of the future. PMID:27045800

Computational protein design: a review

NASA Astrophysics Data System (ADS)

Coluzza, Ivan

2017-04-01

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.

LANL seismic screening method for existing buildings

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

Dickson, S.L.; Feller, K.C.; Fritz de la Orta, G.O.

1997-01-01

The purpose of the Los Alamos National Laboratory (LANL) Seismic Screening Method is to provide a comprehensive, rational, and inexpensive method for evaluating the relative seismic integrity of a large building inventory using substantial life-safety as the minimum goal. The substantial life-safety goal is deemed to be satisfied if the extent of structural damage or nonstructural component damage does not pose a significant risk to human life. The screening is limited to Performance Category (PC) -0, -1, and -2 buildings and structures. Because of their higher performance objectives, PC-3 and PC-4 buildings automatically fail the LANL Seismic Screening Method andmore » will be subject to a more detailed seismic analysis. The Laboratory has also designated that PC-0, PC-1, and PC-2 unreinforced masonry bearing wall and masonry infill shear wall buildings fail the LANL Seismic Screening Method because of their historically poor seismic performance or complex behavior. These building types are also recommended for a more detailed seismic analysis. The results of the LANL Seismic Screening Method are expressed in terms of separate scores for potential configuration or physical hazards (Phase One) and calculated capacity/demand ratios (Phase Two). This two-phase method allows the user to quickly identify buildings that have adequate seismic characteristics and structural capacity and screen them out from further evaluation. The resulting scores also provide a ranking of those buildings found to be inadequate. Thus, buildings not passing the screening can be rationally prioritized for further evaluation. For the purpose of complying with Executive Order 12941, the buildings failing the LANL Seismic Screening Method are deemed to have seismic deficiencies, and cost estimates for mitigation must be prepared. Mitigation techniques and cost-estimate guidelines are not included in the LANL Seismic Screening Method.« less

Nutrient digestibility and energy value of sheep rations differing in protein level, main protein source and non-forage fibre source.

PubMed

Milis, Ch; Liamadis, D

2008-02-01

Two in vivo digestion trials were conducted to evaluate the effects of diet's crude protein (CP) level, N degradability, and non-forage fibre source (NFFS) on nutrient digestibility and energy value of sheep rations. In each trial, rams were fed four isocaloric and isofibrous rations, differing in main protein and/or NFFS source. At the first trial, mean CP/metabolizable energy (ME) ratio of the diets was 17 g/MJ ME and at the second trial, 13 g/MJ ME. At both trials, the first ration contained cotton seed cake (CSC) and wheat bran (WB), the second CSC and corn gluten feed (CGF), the third corn gluten meal (CGM) and WB and the fourth CGM and CGF. Data of both trials were analysed in common as 2 x 2 x 2 factorial experimental design. Low N degradability (CGM) had positive effect on CP, neutral detergent fibre (NDF) and acid detergent fibre (ADF) digestibility of the ration. Those results suggest that an increase in rumen undegradable protein (RUP) content does not negatively affect nutrient digestibility of sheep rations. Corn gluten feed significantly elevated crude fibre (CF) digestibility, in comparison with WB. Rations having high CP/ME ratio had higher digestibility of CP in comparison with those having low CP/ME ratio; the opposite was true for ether extract, CF, NDF and ADF digestibilities. CP level x N degradability interaction negatively affected energy value of the rations that had high CP level and high N degradability. Former suggest that when CP content is high then N degradability should be low otherwise ration's ME is negatively affected. CP digestibility and coefficient q of the rations containing WB and having high N degradability (N degradability x NFFS interaction) were the lowest suggesting that the combination of CSC and WB negatively affected CP digestibility and energy value of the ration. This could be explained by a reduced microbial CP synthesis, or lower RUP digestibility or both.

Rational Design and Synthesis of Carboxylate Gemini Surfactants with an Excellent Aggregate Behavior for Nano-La2O3 Morphology-Controllable Preparation.

PubMed

Liao, Xueming; Gao, Zhinong; Xia, Yan; Niu, Fei; Zhai, Wenzhong

2017-04-04

A series of carboxylate gemini surfactants (CGS, C n -Φ-C n , n = 12, 14, 16, 18) with diphenyl ketone as a spacer group were prepared using a simple and feasible synthetic method. These CGS exhibited an excellent surface activity with extremely low critical micelle concentration (CMC) value (approximately 10 -5 mol/L), good performance in reducing surface tension (nearly 30 mN/m), and the ability of molecular self-assembly into different aggregate morphologies via adjusting the concentrations, which is attributed to the introduction of diphenyl ketone and carboxylic acid ammonium salt in the molecular structure. Moreover, the surface activity and self-assembly ability of CGS were further optimized by tuning the length of the tail chain. These excellent properties imply that CGS can be a soft template to prepare nanomaterials, especially in morphology-controllable synthesis. By adjusting the concentration of one of CGS (C 12 -Φ-C 12 ), nano-La 2 O 3 particles with diverse morphologies were obtained, including spherical shape, bead-chain shape, rod shape, velvet-antler shape, cedar shape, and bowknot shape. This work offers a vital insight into the rational design of template agents for the development of morphology-controllable nanomaterials.

Characterizing the Hot Spots Involved in RON-MSPβ Complex Formation Using In Silico Alanine Scanning Mutagenesis and Molecular Dynamics Simulation

PubMed Central

Zarei, Omid; Hamzeh-Mivehroud, Maryam; Benvenuti, Silvia; Ustun-Alkan, Fulya; Dastmalchi, Siavoush

2017-01-01

Purpose: Implication of protein-protein interactions (PPIs) in development of many diseases such as cancer makes them attractive for therapeutic intervention and rational drug design. RON (Recepteur d’Origine Nantais) tyrosine kinase receptor has gained considerable attention as promising target in cancer therapy. The activation of RON via its ligand, macrophage stimulation protein (MSP) is the most common mechanism of activation for this receptor. The aim of the current study was to perform in silico alanine scanning mutagenesis and to calculate binding energy for prediction of hot spots in protein-protein interface between RON and MSPβ chain (MSPβ). Methods: In this work the residues at the interface of RON-MSPβ complex were mutated to alanine and then molecular dynamics simulation was used to calculate binding free energy. Results: The results revealed that Gln193, Arg220, Glu287, Pro288, Glu289, and His424 residues from RON and Arg521, His528, Ser565, Glu658, and Arg683 from MSPβ may play important roles in protein-protein interaction between RON and MSP. Conclusion: Identification of these RON hot spots is important in designing anti-RON drugs when the aim is to disrupt RON-MSP interaction. In the same way, the acquired information regarding the critical amino acids of MSPβ can be used in the process of rational drug design for developing MSP antagonizing agents, the development of novel MSP mimicking peptides where inhibition of RON activation is required, and the design of experimental site directed mutagenesis studies. PMID:28507948

Laboratory Evaluation of Australian Ration Packs.

DTIC Science & Technology

1982-09-01

Monitoring of Freeze Dried Meals , Potato & Onion Powder .......................... 40 Appendix 6 Emergency Flying Ration ............................ 41...Moulds were enumerated using the pour plate method as described in AS 1766 Part 2.1.2 1976. On occasions malt extract agar was used in place of...potato dextrose agar . Coliforms & E. coli were enumerated using the pour plate method as described in AS 1766 Part 2.1.3.7 1976. Violet red bile dextrose

Rainfall Threshold for Flash Flood Early Warning Based on Rational Equation: A Case Study of Zuojiao Watershed in Yunnan Province

NASA Astrophysics Data System (ADS)

Li, Q.; Wang, Y. L.; Li, H. C.; Zhang, M.; Li, C. Z.; Chen, X.

2017-12-01

Rainfall threshold plays an important role in flash flood warning. A simple and easy method, using Rational Equation to calculate rainfall threshold, was proposed in this study. The critical rainfall equation was deduced from the Rational Equation. On the basis of the Manning equation and the results of Chinese Flash Flood Survey and Evaluation (CFFSE) Project, the critical flow was obtained, and the net rainfall was calculated. Three aspects of the rainfall losses, i.e. depression storage, vegetation interception, and soil infiltration were considered. The critical rainfall was the sum of the net rainfall and the rainfall losses. Rainfall threshold was estimated after considering the watershed soil moisture using the critical rainfall. In order to demonstrate this method, Zuojiao watershed in Yunnan Province was chosen as study area. The results showed the rainfall thresholds calculated by the Rational Equation method were approximated to the rainfall thresholds obtained from CFFSE, and were in accordance with the observed rainfall during flash flood events. Thus the calculated results are reasonable and the method is effective. This study provided a quick and convenient way to calculated rainfall threshold of flash flood warning for the grass root staffs and offered technical support for estimating rainfall threshold.

A new generalized exponential rational function method to find exact special solutions for the resonance nonlinear Schrödinger equation

NASA Astrophysics Data System (ADS)

Ghanbari, Behzad; Inc, Mustafa

2018-04-01

The present paper suggests a novel technique to acquire exact solutions of nonlinear partial differential equations. The main idea of the method is to generalize the exponential rational function method. In order to examine the ability of the method, we consider the resonant nonlinear Schrödinger equation (R-NLSE). Many variants of exact soliton solutions for the equation are derived by the proposed method. Physical interpretations of some obtained solutions is also included. One can easily conclude that the new proposed method is very efficient and finds the exact solutions of the equation in a relatively easy way.

Strategies for Improving siRNA-Induced Gene Silencing Efficiency

PubMed Central

Safari, Fatemeh; Rahmani Barouji, Solmaz; Tamaddon, Ali Mohammad

2017-01-01

Purpose: Human telomerase reverse transcriptase (hTERT) plays a crucial role in tumorigenesis and progression of cancers. Gene silencing of hTERT by short interfering RNA (siRNA) is considered as a promising strategy for cancer gene therapy. Various algorithms have been devised for designing a high efficient siRNA which is a significant issue in the clinical usage. Thereby, in the present study, the relation of siRNA designing criteria and the gene silencing efficiency was evaluated. Methods: The siRNA sequences were designed and characterized by using on line soft wares. Cationic co-polymer (polyethylene glycol-g-polyethylene imine (PEG-g-PEI)) was used for the construction of polyelectrolyte complexes (PECs) containing siRNAs. The cellular uptake of the PECs was evaluated. The gene silencing efficiency of different siRNA sequences was investigated and the effect of observing the rational designing on the functionality of siRNAs was assessed. Results: The size of PEG-g-PEI siRNA with N/P (Nitrogen/Phosphate) ratio of 2.5 was 114 ± 0.645 nm. The transfection efficiency of PECs was desirable (95.5% ± 2.4%.). The results of Real-Time PCR showed that main sequence (MS) reduced the hTERT expression up to 90% and control positive sequence (CPS) up to 63%. These findings demonstrated that the accessibility to the target site has priority than the other criteria such as sequence preferences and thermodynamic features. Conclusion: siRNA opens a hopeful window in cancer therapy which provides a convenient and tolerable therapeutic approach. Thereby, using the set of criteria and rational algorithms in the designing of siRNA remarkably affect the gene silencing efficiency. PMID:29399550

Strategies for Improving siRNA-Induced Gene Silencing Efficiency.

PubMed

Safari, Fatemeh; Rahmani Barouji, Solmaz; Tamaddon, Ali Mohammad

2017-12-01

Purpose: Human telomerase reverse transcriptase (hTERT) plays a crucial role in tumorigenesis and progression of cancers. Gene silencing of hTERT by short interfering RNA (siRNA) is considered as a promising strategy for cancer gene therapy. Various algorithms have been devised for designing a high efficient siRNA which is a significant issue in the clinical usage. Thereby, in the present study, the relation of siRNA designing criteria and the gene silencing efficiency was evaluated. Methods: The siRNA sequences were designed and characterized by using on line soft wares. Cationic co-polymer (polyethylene glycol-g-polyethylene imine (PEG-g-PEI)) was used for the construction of polyelectrolyte complexes (PECs) containing siRNAs. The cellular uptake of the PECs was evaluated. The gene silencing efficiency of different siRNA sequences was investigated and the effect of observing the rational designing on the functionality of siRNAs was assessed. Results: The size of PEG-g-PEI siRNA with N/P (Nitrogen/Phosphate) ratio of 2.5 was 114 ± 0.645 nm. The transfection efficiency of PECs was desirable (95.5% ± 2.4%.). The results of Real-Time PCR showed that main sequence (MS) reduced the hTERT expression up to 90% and control positive sequence (CPS) up to 63%. These findings demonstrated that the accessibility to the target site has priority than the other criteria such as sequence preferences and thermodynamic features. Conclusion: siRNA opens a hopeful window in cancer therapy which provides a convenient and tolerable therapeutic approach. Thereby, using the set of criteria and rational algorithms in the designing of siRNA remarkably affect the gene silencing efficiency.

Suggestions for Library Network Design.

ERIC Educational Resources Information Center

Salton, Gerald

1979-01-01

Various approaches to the design of automatic library systems are described, suggestions for the design of rational and effective automated library processes are posed, and an attempt is made to assess the importance and effect of library network systems on library operations and library effectiveness. (Author/CWM)

Design of Mobile Augmented Reality in Health Care Education: A Theory-Driven Framework.

PubMed

Zhu, Egui; Lilienthal, Anneliese; Shluzas, Lauren Aquino; Masiello, Italo; Zary, Nabil

2015-09-18

Augmented reality (AR) is increasingly used across a range of subject areas in health care education as health care settings partner to bridge the gap between knowledge and practice. As the first contact with patients, general practitioners (GPs) are important in the battle against a global health threat, the spread of antibiotic resistance. AR has potential as a practical tool for GPs to combine learning and practice in the rational use of antibiotics. This paper was driven by learning theory to develop a mobile augmented reality education (MARE) design framework. The primary goal of the framework is to guide the development of AR educational apps. This study focuses on (1) identifying suitable learning theories for guiding the design of AR education apps, (2) integrating learning outcomes and learning theories to support health care education through AR, and (3) applying the design framework in the context of improving GPs' rational use of antibiotics. The design framework was first constructed with the conceptual framework analysis method. Data were collected from multidisciplinary publications and reference materials and were analyzed with directed content analysis to identify key concepts and their relationships. Then the design framework was applied to a health care educational challenge. The proposed MARE framework consists of three hierarchical layers: the foundation, function, and outcome layers. Three learning theories-situated, experiential, and transformative learning-provide foundational support based on differing views of the relationships among learning, practice, and the environment. The function layer depends upon the learners' personal paradigms and indicates how health care learning could be achieved with MARE. The outcome layer analyzes different learning abilities, from knowledge to the practice level, to clarify learning objectives and expectations and to avoid teaching pitched at the wrong level. Suggestions for learning activities and the requirements of the learning environment form the foundation for AR to fill the gap between learning outcomes and medical learners' personal paradigms. With the design framework, the expected rational use of antibiotics by GPs is described and is easy to execute and evaluate. The comparison of specific expected abilities with the GP personal paradigm helps solidify the GP practical learning objectives and helps design the learning environment and activities. The learning environment and activities were supported by learning theories. This paper describes a framework for guiding the design, development, and application of mobile AR for medical education in the health care setting. The framework is theory driven with an understanding of the characteristics of AR and specific medical disciplines toward helping medical education improve professional development from knowledge to practice. Future research will use the framework as a guide for developing AR apps in practice to validate and improve the design framework.

The Promiscuity of [beta]-Strand Pairing Allows for Rational Design of [beta]-Sheet Face Inversion

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

Makabe, Koki; Koide, Shohei

2009-06-17

Recent studies suggest the dominant role of main-chain H-bond formation in specifying {beta}-sheet topology. Its essentially sequence-independent nature implies a large degree of freedom in designing {beta}-sheet-based nanomaterials. Here we show rational design of {beta}-sheet face inversions by incremental deletions of {beta}-strands from the single-layer {beta}-sheet of Borrelia outer surface protein A. We show that a {beta}-sheet structure can be maintained when a large number of native contacts are removed and that one can design large-scale conformational transitions of a {beta}-sheet such as face inversion by exploiting the promiscuity of strand-strand interactions. High-resolution X-ray crystal structures confirmed the success ofmore » the design and supported the importance of main-chain H-bonds in determining {beta}-sheet topology. This work suggests a simple but effective strategy for designing and controlling nanomaterials based on {beta}-rich peptide self-assemblies.« less

Research of Acoustic Properties of Materials with the Purpose of Their Use at Design of Special Noise Protective Clothes for Oil and Gas Industry

NASA Astrophysics Data System (ADS)

Drofa, E. A.; Lipilina, E. Yu

2018-01-01

The article is devoted to the substantiation of the choice of a rational package of materials, which has the greatest noise-protective properties when designing special clothes with reference to the oil and gas industry. Studies were conducted to assess the factors that have the most significant effect on the noise-protective properties of clothing. Conclusions are made about the possibility of using the developed technique for studying the noise-protective properties of materials in selecting rational packages of materials for the production of special clothes with high noise-protective properties.

Game among interdependent networks: The impact of rationality on system robustness

NASA Astrophysics Data System (ADS)

Fan, Yuhang; Cao, Gongze; He, Shibo; Chen, Jiming; Sun, Youxian

2016-12-01

Many real-world systems are composed of interdependent networks that rely on one another. Such networks are typically designed and operated by different entities, who aim at maximizing their own payoffs. There exists a game among these entities when designing their own networks. In this paper, we study the game investigating how the rational behaviors of entities impact the system robustness. We first introduce a mathematical model to quantify the interacting payoffs among varying entities. Then we study the Nash equilibrium of the game and compare it with the optimal social welfare. We reveal that the cooperation among different entities can be reached to maximize the social welfare in continuous game only when the average degree of each network is constant. Therefore, the huge gap between Nash equilibrium and optimal social welfare generally exists. The rationality of entities makes the system inherently deficient and even renders it extremely vulnerable in some cases. We analyze our model for two concrete systems with continuous strategy space and discrete strategy space, respectively. Furthermore, we uncover some factors (such as weakening coupled strength of interdependent networks, designing a suitable topology dependence of the system) that help reduce the gap and the system vulnerability.

Rational modular design of metabolic network for efficient production of plant polyphenol pinosylvin.

PubMed

Wu, Junjun; Zhang, Xia; Zhu, Yingjie; Tan, Qinyu; He, Jiacheng; Dong, Mingsheng

2017-05-03

Efficient biosynthesis of the plant polyphenol pinosylvin, which has numerous applications in nutraceuticals and pharmaceuticals, is necessary to make biological production economically viable. To this end, an efficient Escherichia coli platform for pinosylvin production was developed via a rational modular design approach. Initially, different candidate pathway enzymes were screened to construct de novo pinosylvin pathway directly from D-glucose. A comparative analysis of pathway intermediate pools identified that this initial construct led to the intermediate cinnamic acid accumulation. The pinosylvin synthetic pathway was then divided into two new modules separated at cinnamic acid. Combinatorial optimization of transcriptional and translational levels of these two modules resulted in a 16-fold increase in pinosylvin titer. To further improve the concentration of the limiting precursor malonyl-CoA, the malonyl-CoA synthesis module based on clustered regularly interspaced short palindromic repeats interference was assembled and optimized with other two modules. The final pinosylvin titer was improved to 281 mg/L, which was the highest pinosylvin titer even directly from D-glucose without any additional precursor supplementation. The rational modular design approach described here could bolster our capabilities in synthetic biology for value-added chemical production.

Dynamics of lumps and dark-dark solitons in the multi-component long-wave-short-wave resonance interaction system.

PubMed

Rao, Jiguang; Porsezian, Kuppuswamy; He, Jingsong; Kanna, Thambithurai

2018-01-01

General semi-rational solutions of an integrable multi-component (2+1)-dimensional long-wave-short-wave resonance interaction system comprising multiple short waves and a single long wave are obtained by employing the bilinear method. These solutions describe the interactions between various types of solutions, including line rogue waves, lumps, breathers and dark solitons. We only focus on the dynamical behaviours of the interactions between lumps and dark solitons in this paper. Our detailed study reveals two different types of excitation phenomena: fusion and fission. It is shown that the fundamental (simplest) semi-rational solutions can exhibit fission of a dark soliton into a lump and a dark soliton or fusion of one lump and one dark soliton into a dark soliton. The non-fundamental semi-rational solutions are further classified into three subclasses: higher-order, multi- and mixed-type semi-rational solutions. The higher-order semi-rational solutions show the process of annihilation (production) of two or more lumps into (from) one dark soliton. The multi-semi-rational solutions describe N ( N ≥2) lumps annihilating into or producing from N -dark solitons. The mixed-type semi-rational solutions are a hybrid of higher-order semi-rational solutions and multi-semi-rational solutions. For the mixed-type semi-rational solutions, we demonstrate an interesting dynamical behaviour that is characterized by partial suppression or creation of lumps from the dark solitons.

Dynamics of lumps and dark-dark solitons in the multi-component long-wave-short-wave resonance interaction system

NASA Astrophysics Data System (ADS)

Rao, Jiguang; Porsezian, Kuppuswamy; He, Jingsong; Kanna, Thambithurai

2018-01-01

General semi-rational solutions of an integrable multi-component (2+1)-dimensional long-wave-short-wave resonance interaction system comprising multiple short waves and a single long wave are obtained by employing the bilinear method. These solutions describe the interactions between various types of solutions, including line rogue waves, lumps, breathers and dark solitons. We only focus on the dynamical behaviours of the interactions between lumps and dark solitons in this paper. Our detailed study reveals two different types of excitation phenomena: fusion and fission. It is shown that the fundamental (simplest) semi-rational solutions can exhibit fission of a dark soliton into a lump and a dark soliton or fusion of one lump and one dark soliton into a dark soliton. The non-fundamental semi-rational solutions are further classified into three subclasses: higher-order, multi- and mixed-type semi-rational solutions. The higher-order semi-rational solutions show the process of annihilation (production) of two or more lumps into (from) one dark soliton. The multi-semi-rational solutions describe N(N≥2) lumps annihilating into or producing from N-dark solitons. The mixed-type semi-rational solutions are a hybrid of higher-order semi-rational solutions and multi-semi-rational solutions. For the mixed-type semi-rational solutions, we demonstrate an interesting dynamical behaviour that is characterized by partial suppression or creation of lumps from the dark solitons.

Screening for small molecule inhibitors of Toxoplasma gondii.

PubMed

Kortagere, Sandhya

2012-12-01

Toxoplasma gondii, the agent that causes toxoplasmosis, is an opportunistic parasite that infects many mammalian species. It is an obligate intracellular parasite that causes severe congenital neurological and ocular disease mostly in immunocompromised humans. The current regimen of therapy includes only a few medications that often lead to hypersensitivity and toxicity. In addition, there are no vaccines available to prevent the transmission of this agent. Therefore, safer and more effective medicines to treat toxoplasmosis are urgently needed. The author presents in silico and in vitro strategies that are currently used to screen for novel targets and unique chemotypes against T. gondii. Furthermore, this review highlights the screening technologies and characterization of some novel targets and new chemical entities that could be developed into highly efficacious treatments for toxoplasmosis. A number of diverse methods are being used to design inhibitors against T. gondii. These include ligand-based methods, in which drugs that have been shown to be efficacious against other Apicomplexa parasites can be repurposed to identify lead molecules against T. gondii. In addition, structure-based methods use currently available repertoire of structural information in various databases to rationally design small-molecule inhibitors of T. gondii. Whereas the screening methods have their advantages and limitations, a combination of methods is ideally suited to design small-molecule inhibitors of complex parasites such as T. gondii.

Sharing Teaching Ideas.

ERIC Educational Resources Information Center

Mathematics Teacher, 1985

1985-01-01

Discusses: (1) use of matrix techniques to write secret codes (includes ready-to-duplicate worksheets); (2) a method of multiplication and division of polynomials in one variable that is not tedius, time-consuming, or dependent on guesswork; and (3) adding and subtracting rational expressions and solving rational equations. (JN)

Health Instruction Packages: Consumer--Behavior/Emotions.

ERIC Educational Resources Information Center

Larkin, Vincent; And Others

Text, illustrations, and exercises are utilized in this set of three learning modules to instruct the general public in methods of exploring human psychology and personal interrelationships. The first module, "The Basic Idea behind Rational-Emotive Therapy" by Vincent Larkin, distinguishes between rational and irrational fears and…

Treatment of Childhood Depression: The State of the Art.

ERIC Educational Resources Information Center

Clarizio, Harvey F.

1986-01-01

This article reviews various aspects of seven approaches to the treatment of childhood depression--psychoanalytic, behavioral, cognitive, familial, rational-emotive, multimodal, and drug interventions. Implications for practitioners are considered in terms of target selection, choice of treatment methods, rational evaluation based on developmental…

An Efficient Spectral Method for Ordinary Differential Equations with Rational Function Coefficients

NASA Technical Reports Server (NTRS)

Coutsias, Evangelos A.; Torres, David; Hagstrom, Thomas

1994-01-01

We present some relations that allow the efficient approximate inversion of linear differential operators with rational function coefficients. We employ expansions in terms of a large class of orthogonal polynomial families, including all the classical orthogonal polynomials. These families obey a simple three-term recurrence relation for differentiation, which implies that on an appropriately restricted domain the differentiation operator has a unique banded inverse. The inverse is an integration operator for the family, and it is simply the tridiagonal coefficient matrix for the recurrence. Since in these families convolution operators (i.e. matrix representations of multiplication by a function) are banded for polynomials, we are able to obtain a banded representation for linear differential operators with rational coefficients. This leads to a method of solution of initial or boundary value problems that, besides having an operation count that scales linearly with the order of truncation N, is computationally well conditioned. Among the applications considered is the use of rational maps for the resolution of sharp interior layers.

Relation of knowledge and level of education to the rationality of self-medication on childhood diarrhea on the Code River banks in Jogoyudan, Jetis, Yogyakarta

NASA Astrophysics Data System (ADS)

Dania, H.; Ihsan, M. N.

2017-11-01

Self-medication as an alternative is used to reduce the severity of diarrhea. Optimal treatment can be done by increasing the rationalization of self-medication on diarrhea. This can be achieved with good knowledge about self-medication, which is in turn influenced by level of education. The aim of this study was to determine the relationship of knowledge and education level to rationality of self-medication on childhood diarrhea around the Code River in Jogoyudan, Jetis, Yogyakarta. The study was conducted by cross-sectional analytical observational design. The subjects were mothers who had children aged 2-11 years who had experienced diarrhea and had self-medication. Questionnaires were used to assess the rationality of self-medication on children's diarrhea by the parents. The respondents were askeds to fill out about indications, right drugs, doses, time intervals and periods of drug administration. Data were analyzed using chi- square. It was showed that of 40 respondents, 14 respondents (35%) performed rational self-medication on children's diarrhea and 26 respondents (65%). did not rationalize the treatment. The results of a bivariate test obtained a chi-square value of 9.808 (> 3.841) and a p value of 0.002 (<0.05) on the relationship between education level and rationality of self-medication and a chi-square value of 19.476 (> 3.841) and a p value of 0.000 (<0.05) on relationship between knowledge and rationality of self- medication. The conclusion of this study is that there is a correlation between knowledge and level of education and rationality of self-medication on childhood diarrhea on the Code River banks in Jogoyudan, Jetis, Yogyakarta.

Factors related to rational antibiotic prescriptions in community health centers in Depok City, Indonesia.

PubMed

Andrajati, Retnosari; Tilaqza, Andri; Supardi, Sudibyo

Irrational antibiotic prescription is common in developing countries, including in Indonesia. The aims of this study were to evaluate antibiotic prescription patterns and the factors related to the rationale for antibiotic prescriptions in community health centers in Depok City, Indonesia. The study employed a cross-sectional design in eleven primary health centers in Depok City, Indonesia. The sample consisted of 28 physicians and 788 oral antibiotic prescriptions, 392 of which were evaluated for rationality according to local guidelines issued by the Ministry of Health Republic of Indonesia from October to December 2012. Data were analyzed with chi-square tests and logistic regression analysis. The most widely prescribed antibiotics were amoxicillin (73.5%) and co-trimoxazole (17.4%). The most frequent diseases were acute pharyngitis (40.2%) and non-specific respiratory infection (25.4%). Approximately 220 of the 392 prescriptions did not meet the criteria for rational antibiotic prescriptions with regard to antibiotic selection (22.7%), duration of administration (72.3%), frequency of administration (3.2%), or duration and frequency of administration (1.8%). Physicians who had attended training for rational drug use were 2.01 times more rational than physicians who had never attended training. Physicians with a short working period (i.e., <7 years) were 3.95 times more rational in prescribing antibiotics than physicians who had been working for longer periods (i.e., >7 years). Most antibiotics were prescribed irrationally. Training for rational drug use and length of practice were factors related to the rationality of antibiotic prescriptions. Suitable interventions are urgently required to encourage the rational prescription of antibiotics in the PHCs. Copyright © 2016 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

Effect of Chicken Bone Meal as Phosphorus Supplement on Blood Metabolites in Fattening Lambs

NASA Astrophysics Data System (ADS)

Pujiastuti, A.; Muktiani, A.

2018-02-01

The aim of this study was to evaluate the effect of chicken bone meal (CBM) as phosphorus supplementon blood metabolites in fattening lambs. The experiment used 16 of 12 months old local male lambs with initial body weight 27.01 ± 1.51 kg. The experiment used a complete randomized design with 4 treatments and 4 replications. The treatments were T0 (basal ration = native grass + soybean curd waste), T1 (basal ration + 0.49% P Dicalcium phosphate), T2 (basal ration + 0.70% P CBM), T3 (basal ration + 1.39 % P CBM). The results indicated that CBM as phosphorus supplement was significantly different (P<0,05) on P intake, phosphorus and glucose serum and did not different significantly on dry matter intake and alkaline phosphatase activity. In conclusion, CBM is one of requirement organic phosphorus supplement which can be applied on ruminants.

Rationality and antiemotionality as a risk factor for cancer: concept differentiation.

PubMed

van der Ploeg, H M; Kleijn, W C; Mook, J; van Donge, M; Pieters, A M; Leer, J W

1989-01-01

Control and repression of emotions may be coping styles or personality characteristics found more often in patients with cancer than in other patients and healthy subjects. Previous research indicated a possible relationship between high scores on a 'rationality and antiemotionality' scale and cancer. In the two studies reported, the psychometric properties of this scale and the meaning of the concept as a personality variable related to the control of emotions were investigated. It was found that the internal consistency of the scale could be improved by re-designing it into a personality inventory. Factor analysis repeatedly yielded more than one factor, indicating the complexity of the concept. 'Rationality and antiemotionality' seems related to the control, suppression or repression of anger. Our findings tentatively support the view that rationality and antiemotionality may be an important distinctive personality characteristic in patients with cancer.

Identifying thresholds for relationships between impacts of rationing of nursing care and nurse- and patient-reported outcomes in Swiss hospitals: a correlational study.

PubMed

Schubert, Maria; Clarke, Sean P; Glass, Tracy R; Schaffert-Witvliet, Bianca; De Geest, Sabina

2009-07-01

In the Rationing of Nursing Care in Switzerland Study, implicit rationing of care was the only factor consistently significantly associated with all six studied patient outcomes. These results highlight the importance of rationing as a new system factor regarding patient safety and quality of care. Since at least some rationing of care appears inevitable, it is important to identify the thresholds of its influences in order to minimize its negative effects on patient outcomes. To describe the levels of implicit rationing of nursing care in a sample of Swiss acute care hospitals and to identify clinically meaningful thresholds of rationing. Descriptive cross-sectional multi-center study. Five Swiss-German and three Swiss-French acute care hospitals. 1338 nurses and 779 patients. Implicit rationing of nursing care was measured using the newly developed Basel Extent of Rationing of Nursing Care (BERNCA) instrument. Other variables were measured using survey items from the International Hospital Outcomes Study battery. Data were summarized using appropriate descriptive measures, and logistic regression models were used to define a clinically meaningful rationing threshold level. For the studied patient outcomes, identified rationing threshold levels varied from 0.5 (i.e., between 0 ('never') and 1 ('rarely') to 2 ('sometimes')). Three of the identified patient outcomes (nosocomial infections, pressure ulcers, and patient satisfaction) were particularly sensitive to rationing, showing negative consequences anywhere it was consistently reported (i.e., average BERNCA scores of 0.5 or above). In other cases, increases in negative outcomes were first observed from the level of 1 (average ratings of rarely). Rationing scores generated using the BERNCA instrument provide a clinically meaningful method for tracking the correlates of low resources or difficulties in resource allocation on patient outcomes. Thresholds identified here provide parameters for administrators to respond to whenever rationing reports exceed the determined level of '0.5' or '1'. Since even very low levels of rationing had negative consequences on three of the six studied outcomes, it is advisable to treat consistent evidence of any rationing as a significant threat to patient safety and quality of care.

Rational design for multifunctional non-liposomal lipid-based nanocarriers for cancer management: theory to practice

PubMed Central

2013-01-01

Nanomedicines have gained more and more attention in cancer therapy thanks to their ability to enhance the tumour accumulation and the intracellular uptake of drugs while reducing their inactivation and toxicity. In parallel, nanocarriers have been successfully employed as diagnostic tools increasing imaging resolution holding great promises both in preclinical research and in clinical settings. Lipid-based nanocarriers are a class of biocompatible and biodegradable vehicles that provide advanced delivery of therapeutic and imaging agents, improving pharmacokinetic profile and safety. One of most promising engineering challenges is the design of innovative and versatile multifunctional targeted nanotechnologies for cancer treatment and diagnosis. This review aims to highlight rational approaches to design multifunctional non liposomal lipid-based nanocarriers providing an update of literature in this field. PMID:24564841

Creation of a Novel Class of Potent and Selective MutT Homologue 1 (MTH1) Inhibitors Using Fragment-Based Screening and Structure-Based Drug Design.

PubMed

Rahm, Fredrik; Viklund, Jenny; Trésaugues, Lionel; Ellermann, Manuel; Giese, Anja; Ericsson, Ulrika; Forsblom, Rickard; Ginman, Tobias; Günther, Judith; Hallberg, Kenth; Lindström, Johan; Persson, Lars Boukharta; Silvander, Camilla; Talagas, Antoine; Díaz-Sáez, Laura; Fedorov, Oleg; Huber, Kilian V M; Panagakou, Ioanna; Siejka, Paulina; Gorjánácz, Mátyás; Bauser, Marcus; Andersson, Martin

2018-03-22

Recent literature has both suggested and questioned MTH1 as a novel cancer target. BAY-707 was just published as a target validation small molecule probe for assessing the effects of pharmacological inhibition of MTH1 on tumor cell survival, both in vitro and in vivo. (1) In this report, we describe the medicinal chemistry program creating BAY-707, where fragment-based methods were used to develop a series of highly potent and selective MTH1 inhibitors. Using structure-based drug design and rational medicinal chemistry approaches, the potency was increased over 10,000 times from the fragment starting point while maintaining high ligand efficiency and drug-like properties.

Programmed serial stereochemical relay and its application in the synthesis of morphinans† †Electronic supplementary information (ESI) available. CCDC 1526432. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c7sc03189k Click here for additional data file. Click here for additional data file.

PubMed Central

Ho (Kenny) Park, Kun; Chen, Rui

2017-01-01

Herein we report a rationally designed, serial point-to-axial and axial-to-point stereoinduction and its integration into multi-step and target-oriented organic synthesis. In this proof-of-concept study, the configurational stability of several carefully designed atropisomeric intermediates and the fidelity of their unconventional stereoinductions were systematically investigated. The highly functionalized prepared synthetic intermediate was further applied in a novel chemical method to access the morphinans and it is potentially applicable to other structurally related alkaloids. PMID:29147530

Building synthetic gene circuits from combinatorial libraries: screening and selection strategies.

PubMed

Schaerli, Yolanda; Isalan, Mark

2013-07-01

The promise of wide-ranging biotechnology applications inspires synthetic biologists to design novel genetic circuits. However, building such circuits rationally is still not straightforward and often involves painstaking trial-and-error. Mimicking the process of natural selection can help us to bridge the gap between our incomplete understanding of nature's design rules and our desire to build functional networks. By adopting the powerful method of directed evolution, which is usually applied to protein engineering, functional networks can be obtained through screening or selecting from randomised combinatorial libraries. This review first highlights the practical options to introduce combinatorial diversity into gene circuits and then examines strategies for identifying the potentially rare library members with desired functions, either by screening or selection.

Rational Design of a Green-Light-Mediated Unimolecular Platform for Fast Switchable Acidic Sensing.

PubMed

Zhou, Yunyun; Zou, Qi; Qiu, Jing; Wang, Linjun; Zhu, Liangliang

2018-02-01

A controllable sensing ability strongly connects to complex and precise events in diagnosis and treatment. However, imposing visible light into the molecular-scale mediation of sensing processes is restricted by the lack of structural relevance. To address this critical challenge, we present the rational design, synthesis, and in vitro studies of a novel cyanostyryl-modified azulene system for green-light-mediated fast switchable acidic sensing. The advantageous features of the design include a highly efficient green-light-driven Z/E-isomerization (a quantum yield up to 61.3%) for fast erasing chromatic and luminescent expressions and a superior compatibility with control of ratiometric protonation. Significantly, these merits of the design enable the development of a microfluidic system to perform a green-light-mediated reusable sensing function toward a gastric acid analyte in a miniaturized platform. The results may provide new insights for building future integrated green materials.

Design Principles for Covalent Organic Frameworks as Efficient Electrocatalysts in Clean Energy Conversion and Green Oxidizer Production.

PubMed

Lin, Chun-Yu; Zhang, Lipeng; Zhao, Zhenghang; Xia, Zhenhai

2017-05-01

Covalent organic frameworks (COFs), an emerging class of framework materials linked by covalent bonds, hold potential for various applications such as efficient electrocatalysts, photovoltaics, and sensors. To rationally design COF-based electrocatalysts for oxygen reduction and evolution reactions in fuel cells and metal-air batteries, activity descriptors, derived from orbital energy and bonding structures, are identified with the first-principle calculations for the COFs, which correlate COF structures with their catalytic activities. The calculations also predict that alkaline-earth metal-porphyrin COFs could catalyze the direct production of H 2 O 2 , a green oxidizer and an energy carrier. These predictions are supported by experimental data, and the design principles derived from the descriptors provide an approach for rational design of new electrocatalysts for both clean energy conversion and green oxidizer production. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nonlinear machine learning and design of reconfigurable digital colloids.

PubMed

Long, Andrew W; Phillips, Carolyn L; Jankowksi, Eric; Ferguson, Andrew L

2016-09-14

Digital colloids, a cluster of freely rotating "halo" particles tethered to the surface of a central particle, were recently proposed as ultra-high density memory elements for information storage. Rational design of these digital colloids for memory storage applications requires a quantitative understanding of the thermodynamic and kinetic stability of the configurational states within which information is stored. We apply nonlinear machine learning to Brownian dynamics simulations of these digital colloids to extract the low-dimensional intrinsic manifold governing digital colloid morphology, thermodynamics, and kinetics. By modulating the relative size ratio between halo particles and central particles, we investigate the size-dependent configurational stability and transition kinetics for the 2-state tetrahedral (N = 4) and 30-state octahedral (N = 6) digital colloids. We demonstrate the use of this framework to guide the rational design of a memory storage element to hold a block of text that trades off the competing design criteria of memory addressability and volatility.

Cognitive success: instrumental justifications of normative systems of reasoning

PubMed Central

Schurz, Gerhard

2014-01-01

In the first part of the paper (sec. 1–4), I argue that Elqayam and Evan's (2011) distinction between normative and instrumental conceptions of cognitive rationality corresponds to deontological vs. teleological accounts in meta-ethics. I suggest that Elqayam and Evans' distinction be replaced by the distinction between a-priori intuition-based vs. a-posteriori success-based accounts of cognitive rationality. The value of cognitive success lies in its instrumental rationality for almost-all practical purposes. In the second part (sec. 5–7), I point out that the Elqayam and Evans's distinction between normative and instrumental rationality is coupled with a second distinction: between logically general vs. locally adaptive accounts of rationality. I argue that these are two independent distinctions that should be treated as independent dimensions. I also demonstrate that logically general systems of reasoning can be instrumentally justified. However, such systems can only be cognitively successful if they are paired with successful inductive reasoning, which is the area where the program of adaptive (ecological) rationality emerged, because there are no generally optimal inductive reasoning methods. I argue that the practical necessity of reasoning under changing environments constitutes a dilemma for ecological rationality, which I attempt to solve within a dual account of rationality. PMID:25071624

Modified equations, rational solutions, and the Painleve property for the Kadomtsev--Petviashvili and Hirota--Satsuma equations

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

Weiss, J.

1985-09-01

We propose a method for finding the Lax pairs and rational solutions of integrable partial differential equations. That is, when an equation possesses the Painleve property, a Baecklund transformation is defined in terms of an expansion about the singular manifold. This Baecklund transformation obtains (1) a type of modified equation that is formulated in terms of Schwarzian derivatives and (2) a Miura transformation from the modified to the original equation. By linearizing the (Ricati-type) Miura transformation the Lax pair is found. On the other hand, consideration of the (distinct) Baecklund transformations of the modified equations provides a method for themore » iterative construction of rational solutions. This also obtains the Lax pairs for the modified equations. In this paper we apply this method to the Kadomtsev--Petviashvili equation and the Hirota--Satsuma equations.« less

Rational optimization of drug-target residence time: Insights from inhibitor binding to the S. aureus FabI enzyme-product complex

PubMed Central

Chang, Andrew; Schiebel, Johannes; Yu, Weixuan; Bommineni, Gopal R.; Pan, Pan; Baxter, Michael V.; Khanna, Avinash; Sotriffer, Christoph A.; Kisker, Caroline; Tonge, Peter J.

2013-01-01

Drug-target kinetics has recently emerged as an especially important facet of the drug discovery process. In particular, prolonged drug-target residence times may confer enhanced efficacy and selectivity in the open in vivo system. However, the lack of accurate kinetic and structural data for series of congeneric compounds hinders the rational design of inhibitors with decreased off-rates. Therefore, we chose the Staphylococcus aureus enoyl-ACP reductase (saFabI) - an important target for the development of new anti-staphylococcal drugs - as a model system to rationalize and optimize the drug-target residence time on a structural basis. Using our new, efficient and widely applicable mechanistically informed kinetic approach, we obtained a full characterization of saFabI inhibition by a series of 20 diphenyl ethers complemented by a collection of 9 saFabI-inhibitor crystal structures. We identified a strong correlation between the affinities of the investigated saFabI diphenyl ether inhibitors and their corresponding residence times, which can be rationalized on a structural basis. Due to its favorable interactions with the enzyme, the residence time of our most potent compound exceeds 10 hours. In addition, we found that affinity and residence time in this system can be significantly enhanced by modifications predictable by a careful consideration of catalysis. Our study provides a blueprint for investigating and prolonging drug-target kinetics and may aid in the rational design of long-residence-time inhibitors targeting the essential saFabI enzyme. PMID:23697754

Optimization of the molecular dynamics method for simulations of DNA and ion transport through biological nanopores.

PubMed

Wells, David B; Bhattacharya, Swati; Carr, Rogan; Maffeo, Christopher; Ho, Anthony; Comer, Jeffrey; Aksimentiev, Aleksei

2012-01-01

Molecular dynamics (MD) simulations have become a standard method for the rational design and interpretation of experimental studies of DNA translocation through nanopores. The MD method, however, offers a multitude of algorithms, parameters, and other protocol choices that can affect the accuracy of the resulting data as well as computational efficiency. In this chapter, we examine the most popular choices offered by the MD method, seeking an optimal set of parameters that enable the most computationally efficient and accurate simulations of DNA and ion transport through biological nanopores. In particular, we examine the influence of short-range cutoff, integration timestep and force field parameters on the temperature and concentration dependence of bulk ion conductivity, ion pairing, ion solvation energy, DNA structure, DNA-ion interactions, and the ionic current through a nanopore.

Research on Matching Method of Power Supply Parameters for Dual Energy Source Electric Vehicles

NASA Astrophysics Data System (ADS)

Jiang, Q.; Luo, M. J.; Zhang, S. K.; Liao, M. W.

2018-03-01

A new type of power source is proposed, which is based on the traffic signal matching method of the dual energy source power supply composed of the batteries and the supercapacitors. First, analyzing the power characteristics is required to meet the excellent dynamic characteristics of EV, studying the energy characteristics is required to meet the mileage requirements and researching the physical boundary characteristics is required to meet the physical conditions of the power supply. Secondly, the parameter matching design with the highest energy efficiency is adopted to select the optimal parameter group with the method of matching deviation. Finally, the simulation analysis of the vehicle is carried out in MATLABSimulink, The mileage and energy efficiency of dual energy sources are analyzed in different parameter models, and the rationality of the matching method is verified.

Rational Emotive Behavior Therapy: Humanism in Action.

ERIC Educational Resources Information Center

Hill, Larry K.

1996-01-01

Claims that humanism, in both concept and philosophy, is encased in a literature that is predominantly abstract, making humanism difficult to translate into tangible day-to-day action. Argues that rational emotive behavior therapy (REBT), however, provides a detailed method for translating humanist concepts into humanist behavior. (RJM)

Chronic sublethal effects of San Francisco Bay sediments on nereis (neanthes) arenaceodentata; effect of food ration on sediment toxicity. Final report

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

Moore, D.W.; Dillon, T.M.

1993-09-01

This report is designed to address concerns regarding the effect of food ration on toxicity during chronic sublethal sediment bioassays. To this end, a contaminated San Francisco Bay sediment and a clean control sediment were evaluated in a chronic sublethal test under a series of different food rations, with the marine polychaete worm Nereis (Neanthes) arenaceodentata. Animals were exposed from early juvenile stage through the onset of gametogenesis. Treatments were 2.OX, 1.OX, 0.5X, and 0.25X where X is the recommended food ration for laboratory cultures. Test end points were survival, growth, and reproduction. The contaminated sediment was a composite ofmore » several cores taken to project depth (38 ft (11.6 m) below mean low water mark) from an area in Oakland Inner Harbor known to be contaminated with polycyclic aromatic hydrocarbons and metals. Comparisons were made with a clean control sediment. The control sediment is used in the laboratory cultures of N. arenaceodentata and was collected from Sequim, WA. Mean percent survival of Neanthes was high (>90 percent) in both the contaminated and control sediment across all food ration treatments. Individual wet weights were significantly reduced with decreasing food ration in both contaminated and control sediments. Significant differences in wet weight between sediment types were observed at the 1.OX, 0.5X, and 0.25X rations. Reproduction (fecundity and emergent juvenile (EJ) production) was also Chronic sublethal, Neanthes, Dredged material, San Francisco Bay, Food ration, Sediment.« less

Study on Amortization Time and Rationality in Real Estate Investment

NASA Astrophysics Data System (ADS)

Li, Yancang; Zhou, Shujing; Suo, Juanjuan

Amortization time and rationality has been discussed a lot in real estate investment research. As the price of real estate is driven by Geometric Brown Motion (GBM), whether the mortgagors should amortize in advance has become a key issue in amortization time research. This paper presents a new method to solve the problem by using the optimal stopping time theory and option pricing theory models. We discuss the option value in amortizing decision based on this model. A simulation method is used to test this method.

Time-domain parameter identification of aeroelastic loads by forced-vibration method for response of flexible structures subject to transient wind

NASA Astrophysics Data System (ADS)

Cao, Bochao

Slender structures representing civil, mechanical and aerospace systems such as long-span bridges, high-rise buildings, stay cables, power-line cables, high light mast poles, crane-booms and aircraft wings could experience vortex-induced and buffeting excitations below their design wind speeds and divergent self-excited oscillations (flutter) beyond a critical wind speed because these are flexible. Traditional linear aerodynamic theories that are routinely applied for their response prediction are not valid in the galloping, or near-flutter regime, where large-amplitude vibrations could occur and during non-stationary and transient wind excitations that occur, for example, during hurricanes, thunderstorms and gust fronts. The linear aerodynamic load formulation for lift, drag and moment are expressed in terms of aerodynamic functions in frequency domain that are valid for straight-line winds which are stationary or weakly-stationary. Application of the frequency domain formulation is restricted from use in the nonlinear and transient domain because these are valid for linear models and stationary wind. The time-domain aerodynamic force formulations are suitable for finite element modeling, feedback-dependent structural control mechanism, fatigue-life prediction, and above all modeling of transient structural behavior during non-stationary wind phenomena. This has motivated the developing of time-domain models of aerodynamic loads that are in parallel to the existing frequency-dependent models. Parameters defining these time-domain models can be now extracted from wind tunnel tests, for example, the Rational Function Coefficients defining the self-excited wind loads can be extracted using section model tests using the free vibration technique. However, the free vibration method has some limitations because it is difficult to apply at high wind speeds, in turbulent wind environment, or on unstable cross sections with negative aerodynamic damping. In the current research, new algorithms were developed based on forced vibration technique for direct extraction of the Rational Functions. The first of the two algorithms developed uses the two angular phase lag values between the measured vertical or torsional displacement and the measured aerodynamic lift and moment produced on the section model subject to forced vibration to identify the Rational Functions. This algorithm uses two separate one-degree-of-freedom tests (vertical or torsional) to identify all the four Rational Functions or corresponding Rational Function Coefficients for a two degrees-of-freedom (DOF) vertical-torsional vibration model. It was applied to a streamlined section model and the results compared well with those obtained from earlier free vibration experiment. The second algorithm that was developed is based on direct least squares method. It uses all the data points of displacements and aerodynamic lift and moment instead of phase lag values for more accurate estimates. This algorithm can be used for one-, two- and three-degree-of-freedom motions. A two-degree-of-freedom forced vibration system was developed and the algorithm was shown to work well for both streamlined and bluff section models. The uniqueness of the second algorithms lies in the fact that it requires testing the model at only two wind speeds for extraction of all four Rational Functions. The Rational Function Coefficients that were extracted for a streamlined section model using the two-DOF Least Squares algorithm were validated in a separate wind tunnel by testing a larger scaled model subject to straight-line, gusty and boundary-layer wind.

Design of a small molecule against an oncogenic noncoding RNA

PubMed Central

Velagapudi, Sai Pradeep; Cameron, Michael D.; Haga, Christopher L.; Rosenberg, Laura H.; Lafitte, Marie; Duckett, Derek R.; Phinney, Donald G.; Disney, Matthew D.

2016-01-01

The design of precision, preclinical therapeutics from sequence is difficult, but advances in this area, particularly those focused on rational design, could quickly transform the sequence of disease-causing gene products into lead modalities. Herein, we describe the use of Inforna, a computational approach that enables the rational design of small molecules targeting RNA to quickly provide a potent modulator of oncogenic microRNA-96 (miR-96). We mined the secondary structure of primary microRNA-96 (pri-miR-96) hairpin precursor against a database of RNA motif–small molecule interactions, which identified modules that bound RNA motifs nearby and in the Drosha processing site. Precise linking of these modules together provided Targaprimir-96 (3), which selectively modulates miR-96 production in cancer cells and triggers apoptosis. Importantly, the compound is ineffective on healthy breast cells, and exogenous overexpression of pri-miR-96 reduced compound potency in breast cancer cells. Chemical Cross-Linking and Isolation by Pull-Down (Chem-CLIP), a small-molecule RNA target validation approach, shows that 3 directly engages pri-miR-96 in breast cancer cells. In vivo, 3 has a favorable pharmacokinetic profile and decreases tumor burden in a mouse model of triple-negative breast cancer. Thus, rational design can quickly produce precision, in vivo bioactive lead small molecules against hard-to-treat cancers by targeting oncogenic noncoding RNAs, advancing a disease-to-gene-to-drug paradigm. PMID:27170187

Communicative versus strategic rationality: Habermas theory of communicative action and the social brain.

PubMed

Schaefer, Michael; Heinze, Hans-Jochen; Rotte, Michael; Denke, Claudia

2013-01-01

In the philosophical theory of communicative action, rationality refers to interpersonal communication rather than to a knowing subject. Thus, a social view of rationality is suggested. The theory differentiates between two kinds of rationality, the emancipative communicative and the strategic or instrumental reasoning. Using experimental designs in an fMRI setting, recent studies explored similar questions of reasoning in the social world and linked them with a neural network including prefrontal and parietal brain regions. Here, we employed an fMRI approach to highlight brain areas associated with strategic and communicative reasoning according to the theory of communicative action. Participants were asked to assess different social scenarios with respect to communicative or strategic rationality. We found a network of brain areas including temporal pole, precuneus, and STS more activated when participants performed communicative reasoning compared with strategic thinking and a control condition. These brain regions have been previously linked to moral sensitivity. In contrast, strategic rationality compared with communicative reasoning and control was associated with less activation in areas known to be related to moral sensitivity, emotional processing, and language control. The results suggest that strategic reasoning is associated with reduced social and emotional cognitions and may use different language related networks. Thus, the results demonstrate experimental support for the assumptions of the theory of communicative action.

Manipulating the architecture of bimetallic nanostructures and their plasmonic properties

NASA Astrophysics Data System (ADS)

DeSantis, Christopher John

There has been much interest in colloidal noble metal nanoparticles due to their fascinating plasmonic and catalytic properties. These properties make noble metal nanoparticles potentially useful for applications such as targeted drug delivery agents and hydrogen storage devices. Historically, shape-controlled noble metal nanoparticles have been predominantly monometallic. Recent synthetic advances provide access to bimetallic noble metal nanoparticles wherein their inherent multifunctionality and ability to fine tune or expand their surface chemistry and light scattering properties of metal nanoparticles make them popular candidates for many applications. Even so, there are currently few synthetic strategies to rationally design shape-controlled bimetallic nanocrystals; for this reason, few architectures are accessible. For example, the "seed-mediated method" is a popular means of achieving monodisperse shape-controlled bimetallic nanocrystals. In this process, small metal seeds are used as platforms for additional metal addition, allowing for conformal core shell nanostructures. However, this method has only been applied to single metal core/single metal shell structures; therefore, the surface compositions and architectures achievable are limited. This thesis expands upon the seed-mediated method by coupling it with co-reduction. In short, two metal precursors are simultaneously reduced to deposit metal onto pre-formed seeds in hopes that the interplay between two metal species facilitates bimetallic shell nanocrystals. Au/Pd was used as a test system due to favorable reduction potentials of metal precursors and good lattice match between Au and Pd. Alloyed shelled Au Au/Pd nanocrystals were achieved using this "seed-mediated co-reduction" approach. Symmetric eight-branched Au/Pd nanocrystals (octopods) are also prepared using this method. This thesis investigates many synthetic parameters that determine the shape outcome in Au/Pd nanocrystals during seed-mediated co-reduction. Plasmonic, catalytic, and assembly properties are also investigated in relation to nanocrystal shape and architecture. This work provides a foundation for the rational design of architecturally defined bimetallic nanostructures.

Rational Design of Small Molecules Targeting Oncogenic Noncoding RNAs from Sequence.

PubMed

Disney, Matthew D; Angelbello, Alicia J

2016-12-20

The discovery of RNA catalysis in the 1980s and the dissemination of the human genome sequence at the start of this century inspired investigations of the regulatory roles of noncoding RNAs in biology. In fact, the Encyclopedia of DNA Elements (ENCODE) project has shown that only 1-2% of the human genome encodes protein, yet 75% is transcribed into RNA. Functional studies both preceding and following the ENCODE project have shown that these noncoding RNAs have important roles in regulating gene expression, developmental timing, and other critical functions. RNA's diverse roles are often a consequence of the various folds that it adopts. The single-stranded nature of the biopolymer enables it to adopt intramolecular folds with noncanonical pairings to lower its free energy. These folds can be scaffolds to bind proteins or to form frameworks to interact with other RNAs. Not surprisingly, dysregulation of certain noncoding RNAs has been shown to be causative of disease. Given this as the background, it is easy to see why it would be useful to develop methods that target RNA and manipulate its biology in rational and predictable ways. The antisense approach has afforded strategies to target RNAs via Watson-Crick base pairing and has typically focused on targeting partially unstructured regions of RNA. Small molecule strategies to target RNA would be desirable not only because compounds could be lead optimized via medicinal chemistry but also because structured regions within an RNA of interest could be targeted to directly interfere with RNA folds that contribute to disease. Additionally, small molecules have historically been the most successful drug candidates. Until recently, the ability to design small molecules that target non-ribosomal RNAs has been elusive, creating the perception that they are "undruggable". In this Account, approaches to demystify targeting RNA with small molecules are described. Rather than bulk screening for compounds that bind to singular targets, which is the purview of the pharmaceutical industry and academic institutions with high throughput screening facilities, we focus on methods that allow for the rational design of small molecules toward biological RNAs. One enabling and foundational technology that has been developed is two-dimensional combinatorial screening (2DCS), a library-versus-library selection approach that allows the identification of the RNA motif binding preferences of small molecules from millions of combinations. A landscape map of the 2DCS-defined and annotated RNA motif-small molecule interactions is then placed into Inforna, a computational tool that allows one to mine these interactions against an RNA of interest or an entire transcriptome. Indeed, this approach has been enabled by tools to annotate RNA structure from sequence, an invaluable asset to the RNA community and this work, and has allowed for the rational identification of "druggable" RNAs in a target agnostic fashion.

Rational design based synthetic polyepitope DNA vaccine for eliciting HIV-specific CD8+ T cell responses.

PubMed

Bazhan, S I; Karpenko, L I; Ilyicheva, T N; Belavin, P A; Seregin, S V; Danilyuk, N K; Antonets, D V; Ilyichev, A A

2010-04-01

Advances in defining HIV-1 CD8+ T cell epitopes and understanding endogenous MHC class I antigen processing enable the rational design of polyepitope vaccines for eliciting broadly targeted CD8+ T cell responses to HIV-1. Here we describe the construction and comparison of experimental DNA vaccines consisting of ten selected HLA-A2 epitopes from the major HIV-1 antigens Env, Gag, Pol, Nef, and Vpr. The immunogenicity of designed gene constructs was assessed after double DNA prime, single vaccinia virus boost immunization of HLA-A2 transgenic mice. We compared a number of parameters including different strategies for fusing ubiquitin to the polyepitope and including spacer sequences between epitopes to optimize proteasome liberation and TAP transport. It was demonstrated that the vaccine construct that induced in vitro the largest number of [peptide-MHC class I] complexes was also the most immunogenic in the animal experiments. This most immunogenic vaccine construct contained the N-terminal ubiquitin for targeting the polyepitope to the proteasome and included both proteasome liberation and TAP transport optimized spacer sequences that flanked the epitopes within the polyepitope construct. The immunogenicity of determinants was strictly related to their affinities for HLA-A2. Our finding supports the concept of rational vaccine design based on detailed knowledge of antigen processing. Copyright 2010 Elsevier Ltd. All rights reserved.

A Comparison Study of Second-Order Screening Designs and Their Extension

DTIC Science & Technology

2013-12-01

H2 97 V. Nonlinear Screening Designs for Defense Testing: An Overview and Case Study 5.1 Introduction “Necessity is the Mother of Invention.” Plato is...involved concepts like design resolution, minimum aber- ration , power, the number of clear (non-confounded) effects, concepts like rotatability

[Expert consensus on prescription comment of Chinese traditional patent medicine for promoting the rational use of drugs in Beijing].

PubMed

Jin, Rui; Zhao, Kui-Jun; Guo, Gui-Ming; Zhang, Bing; Wang, Yu-Guang; Xue, Chun-Miao; Yang, Yi-Heng; Wang, Li-Xia; Li, Guo-Hui; Tang, Jin-Fa; Nie, Li-Xing; Zhang, Xiang-Lin; Zhao, Ting-Ting; Zhang, Yi; Yan, Can; Yuan, Suo-Zhong; Sun, Lu-Lu; Feng, Xing-Zhong; Yan, Dan

2018-03-01

With the growth of number of Chinese patent medicines and clinical use, the rational use of Chinese medicine is becoming more and more serious. Due to the complexity of Chinese medicine theory and the uncertainty of clinical application, the prescription review of Chinese patent medicine always relied on experience in their respective, leading to the uncontrolled of clinical rational use. According to the traditional Chinese medicine (TCM) theory and characteristics of the unique clinical therapeutics, based on the practice experience and expertise comments, our paper formed the expert consensus on the prescription review of Chinese traditional patent medicine for promoting the rational use of drugs in Beijing. The objective, methods and key points of prescription review of Chinese patent medicine, were included in this expert consensus, in order to regulate the behavior of prescription and promote rational drug use. Copyright© by the Chinese Pharmaceutical Association.

Permeation profiles of Antibiotics

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

Lopez Bautista, Cesar Augusto; Gnanakaran, Sandrasegaram

Presentation describes motivation: Combating bacterial inherent resistance; Drug development mainly uses brute force rather than rational design; Current experimental approaches lack molecular detail.

Molecular system identification for enzyme directed evolution and design

NASA Astrophysics Data System (ADS)

Guan, Xiangying; Chakrabarti, Raj

2017-09-01

The rational design of chemical catalysts requires methods for the measurement of free energy differences in the catalytic mechanism for any given catalyst Hamiltonian. The scope of experimental learning algorithms that can be applied to catalyst design would also be expanded by the availability of such methods. Methods for catalyst characterization typically either estimate apparent kinetic parameters that do not necessarily correspond to free energy differences in the catalytic mechanism or measure individual free energy differences that are not sufficient for establishing the relationship between the potential energy surface and catalytic activity. Moreover, in order to enhance the duty cycle of catalyst design, statistically efficient methods for the estimation of the complete set of free energy differences relevant to the catalytic activity based on high-throughput measurements are preferred. In this paper, we present a theoretical and algorithmic system identification framework for the optimal estimation of free energy differences in solution phase catalysts, with a focus on one- and two-substrate enzymes. This framework, which can be automated using programmable logic, prescribes a choice of feasible experimental measurements and manipulated input variables that identify the complete set of free energy differences relevant to the catalytic activity and minimize the uncertainty in these free energy estimates for each successive Hamiltonian design. The framework also employs decision-theoretic logic to determine when model reduction can be applied to improve the duty cycle of high-throughput catalyst design. Automation of the algorithm using fluidic control systems is proposed, and applications of the framework to the problem of enzyme design are discussed.

Texas M-E flexible pavement design system: literature review and proposed framework.

DOT National Transportation Integrated Search

2012-04-01

Recent developments over last several decades have offered an opportunity for more rational and rigorous pavement design procedures. Substantial work has already been completed in Texas, nationally, and internationally, in all aspects of modeling, ma...

Rational Emotive Behavior Therapy with Troubled Students.

ERIC Educational Resources Information Center

Zionts, Paul; Zionts, Laura

1997-01-01

Based on the early work of Albert Ellis, seeks to identify and challenge irrational beliefs that underlie behavior problems. Outlines concepts and methods of Rational Emotive Behavior Theory and describes the application both in counseling and as a mental health curriculum for troubled children and youth. Offers classroom techniques. (RJM)

Solving Rational Expectations Models Using Excel

ERIC Educational Resources Information Center

Strulik, Holger

2004-01-01

Simple problems of discrete-time optimal control can be solved using a standard spreadsheet software. The employed-solution method of backward iteration is intuitively understandable, does not require any programming skills, and is easy to implement so that it is suitable for classroom exercises with rational-expectations models. The author…

Unfinished nursing care, missed care, and implicitly rationed care: State of the science review.

PubMed

Jones, Terry L; Hamilton, Patti; Murry, Nicole

2015-06-01

The purposes of this review of unfinished care were to: (1) compare conceptual definitions and frameworks associated with unfinished care and related synonyms (i.e. missed care, implicitly rationed care; and care left undone); (2) compare and contrast approaches to instrumentation; (3) describe prevalence and patterns; (4) identify antecedents and outcomes; and (5) describe mitigating interventions. A literature search in CINAHL and MEDLINE identified 1828 articles; 54 met inclusion criteria. Search terms included: implicit ration*, miss* care, ration* care, task* undone, and unfinish*care. Analysis was performed in three phases: initial screening and sorting, comprehensive review for data extraction (first author), and confirmatory review to validate groupings, major themes, and interpretations (second author). Reviewed literature included 42 quantitative reports; 7 qualitative reports; 1 mixed method report; and 4 scientific reviews. With one exception, quantitative studies involved observational cross-sectional survey designs. A total of 22 primary samples were identified; 5 involved systematic sampling. The response rate was >60% in over half of the samples. Unfinished care was measured with 14 self-report instruments. Most nursing personnel (55-98%) reported leaving at least 1 task undone. Estimates increased with survey length, recall period, scope of response referent, and scope of resource scarcity considered. Patterns of unfinished care were consistent with the subordination of teaching and emotional support activities to those related to physiologic needs and organizational audits. Predictors of unfinished care included perceived team interactions, adequacy of resources, safety climate, and nurse staffing. Unfinished care is a predictor of: decreased nurse-reported care quality, decreased patient satisfaction; increased adverse events; increased turnover; decreased job and occupational satisfaction; and increased intent to leave. Unfinished care is a significant problem in acute care hospitals internationally. Prioritization strategies of nurses leave patients vulnerable to unmet educational, emotional, and psychological needs. Key limitations of the science include the threat of common method/source bias, a lack of transparency regarding the use of combined samples and secondary analysis, inconsistency in the reporting format for unfinished care prevalence, and a paucity of intervention studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Optimal design of earth-moving machine elements with cusp catastrophe theory application

NASA Astrophysics Data System (ADS)

Pitukhin, A. V.; Skobtsov, I. G.

2017-10-01

This paper deals with the optimal design problem solution for the operator of an earth-moving machine with a roll-over protective structure (ROPS) in terms of the catastrophe theory. A brief description of the catastrophe theory is presented, the cusp catastrophe is considered, control parameters are viewed as Gaussian stochastic quantities in the first part of the paper. The statement of optimal design problem is given in the second part of the paper. It includes the choice of the objective function and independent design variables, establishment of system limits. The objective function is determined as mean total cost that includes initial cost and cost of failure according to the cusp catastrophe probability. Algorithm of random search method with an interval reduction subject to side and functional constraints is given in the last part of the paper. The way of optimal design problem solution can be applied to choose rational ROPS parameters, which will increase safety and reduce production and exploitation expenses.

Design of Heteronuclear Metalloenzymes

PubMed Central

Bhagi-Damodaran, Ambika; Hosseinzadeh, Parisa; Mirts, Evan; Reed, Julian; Petrik, Igor D.; Lu, Yi

2016-01-01

Heteronuclear metalloenzymes catalyze some of the most fundamentally interesting and practically useful reactions in nature. However, the presence of two or more metal ions in close proximity in these enzymes makes them more difficult to prepare and study than homonuclear metalloenzymes. To meet these challenges, heteronuclear metal centers have been designed into small and stable proteins with rigid scaffolds to understand how these heteronuclear centers are constructed and the mechanism of their function. This chapter describes methods for designing heterobinuclear metal centers in a protein scaffold by giving specific examples of a few heme-nonheme bimetallic centers engineered in myoglobin and cytochrome c peroxidase. We provide step-by-step procedure on how to choose the protein scaffold, design a heterobinuclear metal center in the protein computationally, incorporate metal centers in the protein and characterize the resulting metalloprotein, both structurally and functionally. Finally, we discuss how an initial design can be further improved by rationally tuning its secondary coordination sphere, electron/proton transfer rates, and the substrate affinity. PMID:27586347

DNA rendering of polyhedral meshes at the nanoscale

NASA Astrophysics Data System (ADS)

Benson, Erik; Mohammed, Abdulmelik; Gardell, Johan; Masich, Sergej; Czeizler, Eugen; Orponen, Pekka; Högberg, Björn

2015-07-01

It was suggested more than thirty years ago that Watson-Crick base pairing might be used for the rational design of nanometre-scale structures from nucleic acids. Since then, and especially since the introduction of the origami technique, DNA nanotechnology has enabled increasingly more complex structures. But although general approaches for creating DNA origami polygonal meshes and design software are available, there are still important constraints arising from DNA geometry and sense/antisense pairing, necessitating some manual adjustment during the design process. Here we present a general method of folding arbitrary polygonal digital meshes in DNA that readily produces structures that would be very difficult to realize using previous approaches. The design process is highly automated, using a routeing algorithm based on graph theory and a relaxation simulation that traces scaffold strands through the target structures. Moreover, unlike conventional origami designs built from close-packed helices, our structures have a more open conformation with one helix per edge and are therefore stable under the ionic conditions usually used in biological assays.

DNA rendering of polyhedral meshes at the nanoscale.

PubMed

Benson, Erik; Mohammed, Abdulmelik; Gardell, Johan; Masich, Sergej; Czeizler, Eugen; Orponen, Pekka; Högberg, Björn

2015-07-23

It was suggested more than thirty years ago that Watson-Crick base pairing might be used for the rational design of nanometre-scale structures from nucleic acids. Since then, and especially since the introduction of the origami technique, DNA nanotechnology has enabled increasingly more complex structures. But although general approaches for creating DNA origami polygonal meshes and design software are available, there are still important constraints arising from DNA geometry and sense/antisense pairing, necessitating some manual adjustment during the design process. Here we present a general method of folding arbitrary polygonal digital meshes in DNA that readily produces structures that would be very difficult to realize using previous approaches. The design process is highly automated, using a routeing algorithm based on graph theory and a relaxation simulation that traces scaffold strands through the target structures. Moreover, unlike conventional origami designs built from close-packed helices, our structures have a more open conformation with one helix per edge and are therefore stable under the ionic conditions usually used in biological assays.

A polymer dataset for accelerated property prediction and design

DOE PAGES

Huan, Tran Doan; Mannodi-Kanakkithodi, Arun; Kim, Chiho; ...

2016-03-01

Emerging computation- and data-driven approaches are particularly useful for rationally designing materials with targeted properties. Generally, these approaches rely on identifying structure-property relationships by learning from a dataset of sufficiently large number of relevant materials. The learned information can then be used to predict the properties of materials not already in the dataset, thus accelerating the materials design. Herein, we develop a dataset of 1,073 polymers and related materials and make it available at http://khazana.uconn.edu/. This dataset is uniformly prepared using first-principles calculations with structures obtained either from other sources or by using structure search methods. Because the immediate targetmore » of this work is to assist the design of high dielectric constant polymers, it is initially designed to include the optimized structures, atomization energies, band gaps, and dielectric constants. As a result, it will be progressively expanded by accumulating new materials and including additional properties calculated for the optimized structures provided.« less

Total System Design (TSD) Methodology Assessment.

DTIC Science & Technology

1983-01-01

hardware implementation. Author: Martin - Marietta Aerospace Title: Total System Design Methodology Source: Martin - Marietta Technical Report MCR -79-646...systematic, rational approach to computer systems design is needed. Martin - Marietta has produced a Total System Design Methodology to support such design...gathering and ordering. The purpose of the paper is to document the existing TSD methoeology at Martin - Marietta , describe the supporting tools, and

Optimizing Parameters of Axial Pressure-Compounded Ultra-Low Power Impulse Turbines at Preliminary Design

NASA Astrophysics Data System (ADS)

Kalabukhov, D. S.; Radko, V. M.; Grigoriev, V. A.

2018-01-01

Ultra-low power turbine drives are used as energy sources in auxiliary power systems, energy units, terrestrial, marine, air and space transport within the confines of shaft power N td = 0.01…10 kW. In this paper we propose a new approach to the development of surrogate models for evaluating the integrated efficiency of multistage ultra-low power impulse turbine with pressure stages. This method is based on the use of existing mathematical models of ultra-low power turbine stage efficiency and mass. It has been used in a method for selecting the rational parameters of two-stage axial ultra-low power turbine. The article describes the basic features of an algorithm for two-stage turbine parameters optimization and for efficiency criteria evaluating. Pledged mathematical models are intended for use at the preliminary design of turbine drive. The optimization method was tested at preliminary design of an air starter turbine. Validation was carried out by comparing the results of optimization calculations and numerical gas-dynamic simulation in the Ansys CFX package. The results indicate a sufficient accuracy of used surrogate models for axial two-stage turbine parameters selection

Antiretroviral therapy (ART) rationing and access mechanisms and their impact on youth ART utilization in Malawi.

PubMed

Dixon, Jimmy-Gama; Gibson, Sarah; McPake, Barbara; Maleta, Ken

2011-06-01

The World Health Organization (WHO) staging is a commonly used rationing mechanism for highly active antiretroviral therapy (HAART) among various HIV infected populations including youths in most developing countries. Rationing is defined as any policy or practice that restricts consumption of or access to certain goods due to its limited supply. However, as HIV prevalence is rapidly increasing among youth, understanding the capacity of the staging approach to achieve HAART uptake in youth is of considerable importance. This study aimed to explore how HAART rationing and access mechanisms impact on youth's utilization of HAART in Malawi. The study used mixed methods with quantitative analysis of existing Ministry of Health Clinical HIV Unit data used to determine existing levels of youth HAART use. Qualitative methods employed in-depth interviews that interviewed nine ART providers, nine HIV positive youth on HAART and nine HIV positive youth not on HAART; and field observations to nine ART clinics were used to understand HAART rationing and access mechanisms and how such mechanisms impact youth uptake of HAART. The findings revealed that ART providers use both explicit rationing mechanisms like WHO clinical staging and implicit rationing mechanisms like use of waiting lists, queues and referral in ART provision. However, the WHO staging approach had some challenges in its implementation. It was also observed that factors like non-comprehensive approach to HAART provision, costs incurred to access HAART, negative beliefs and misconceptions about HAART and HIV were among the key factors that limit youth access to HAART. The study recommends that while WHO staging is successful as a rationing mechanism in Malawi, measures should be put in place to improve access to CD4 assessment for clients who may need it. ART providers also need to be made aware of the implicit rationing mechanisms that may affect HAART access. There is also need to improve monitoring of those HIV positive youth not on HAART in order for the system to be able to commence them on treatment on time. Additionally, ART programmes need to address individual, programme and structural/social factors that may affect t youth's access to HAART.

Monitoring total mixed rations and feed delivery systems.

PubMed

Oelberg, Thomas J; Stone, William

2014-11-01

This article is intended to give practitioners a method to evaluate total mixed ration (TMR) consistency and to give them practical solutions to improve TMR consistency that will improve cattle performance and health. Practitioners will learn how to manage the variation in moisture and nutrients that exists in haylage and corn silage piles and in bales of hay, and methods to reduce variation in the TMR mixing and delivery process. Copyright © 2014 Elsevier Inc. All rights reserved.

Dismantling the Built Drawing: Working with Mood in Architectural Design

ERIC Educational Resources Information Center

Teal, Randall

2010-01-01

From the late Middle Ages onward an emphasis on the rational and the technical aspects of design and design drawing gained hold of architectural practice. In this transformation, the phenomenon of mood has been frequently overlooked or seen as something to be added on to a design; yet the fundamental grounding of mood, as described in Martin…

FRET-based small-molecule fluorescent probes: rational design and bioimaging applications.

PubMed

Yuan, Lin; Lin, Weiying; Zheng, Kaibo; Zhu, Sasa

2013-07-16

Fluorescence imaging has emerged as a powerful tool for monitoring biomolecules within the context of living systems with high spatial and temporal resolution. Researchers have constructed a large number of synthetic intensity-based fluorescent probes for bio-imaging. However, intensity-based fluorescent probes have some limitations: variations in probe concentration, probe environment, and excitation intensity may influence the fluorescence intensity measurements. In principle, the use of ratiometric fluorescent probes can alleviate this shortcoming. Förster resonance energy transfer (FRET) is one of the most widely used sensing mechanisms for ratiometric fluorescent probes. However, the development of synthetic FRET probes with favorable photophysical properties that are also suitable for biological imaging applications remains challenging. In this Account, we review the rational design and biological applications of synthetic FRET probes, focusing primarily on studies from our laboratory. To construct useful FRET probes, it is a pre-requisite to develop a FRET platform with favorable photophysical properties. The design criteria of a FRET platform include (1) well-resolved absorption spectra of the donor and acceptor, (2) well-separated emission spectra of the donor and acceptor, (3) donors and acceptors with comparable brightness, (4) rigid linkers, and (5) near-perfect efficiency in energy transfer. With an efficient FRET platform in hand, it is then necessary to modulate the donor-acceptor distance or spectral overlap integral in an analyte-dependent fashion for development of FRET probes. Herein, we emphasize our most recent progress on the development of FRET probes by spectral overlap integral, in particular by changing the molar absorption coefficient of the donor dyes such as rhodamine dyes, which undergo unique changes in the absorption profiles during the ring-opening and -closing processes. Although partial success has been obtained in design of first-generation rhodamine-based FRET probes via modulation of acceptor molar absorption coefficient, further improvements in terms of versatility, sensitivity, and synthetic accessibility are required. To address these issues with the first-generation rhodamine-based FRET probes, we have proposed a strategy for the design of second-generation probes. As a demonstration, we have developed FRET imaging probes for diverse targets including Cu²⁺, NO, HOCl, cysteine, and H₂O₂. This discussion of the methods for successfully designing synthetic FRET probes underscores the rational basis for further development of new FRET probes as a molecular toolbox for probing and manipulating a wide variety of biomolecules in living systems.

Interlinked multiphase Fe-doped MnO2 nanostructures: a novel design for enhanced pseudocapacitive performance

NASA Astrophysics Data System (ADS)

Wang, Ziya; Wang, Fengping; Li, Yan; Hu, Jianlin; Lu, Yanzhen; Xu, Mei

2016-03-01

Structure designing and morphology control can lead to high performance pseudocapacitive materials for supercapacitors. In this work, we have designed interlinked multiphase Fe-doped MnO2 nanostructures (α-MnO2/R-MnO2/ε-MnO2) to enhance the electrochemical properties by a facile method. These hierarchical hollow microspheres assembled by interconnected nanoflakes, and with plenty of porous nanorods radiating from the spherical shells were hydrothermally obtained. The supercapacitor electrode prepared from the unique construction exhibits outstanding specific capacitance of 267.0 F g-1 even under a high mass loading (~5 mg cm-2). Obviously improved performances compared to pure MnO2 are also demonstrated with a good rate capability, high energy density (1.30 mW h cm-3) and excellent cycling stability of 100% capacitance retention after 2000 cycles at 2 A g-1. The synergistic effects of alternative crystal structures, appropriate crystallinity and optimal morphology are identified to be responsible for the observations. This rational multiphase composite strategy provides a promising idea for materials scientists to design and prepare scalable electrode materials for energy storage devices.Structure designing and morphology control can lead to high performance pseudocapacitive materials for supercapacitors. In this work, we have designed interlinked multiphase Fe-doped MnO2 nanostructures (α-MnO2/R-MnO2/ε-MnO2) to enhance the electrochemical properties by a facile method. These hierarchical hollow microspheres assembled by interconnected nanoflakes, and with plenty of porous nanorods radiating from the spherical shells were hydrothermally obtained. The supercapacitor electrode prepared from the unique construction exhibits outstanding specific capacitance of 267.0 F g-1 even under a high mass loading (~5 mg cm-2). Obviously improved performances compared to pure MnO2 are also demonstrated with a good rate capability, high energy density (1.30 mW h cm-3) and excellent cycling stability of 100% capacitance retention after 2000 cycles at 2 A g-1. The synergistic effects of alternative crystal structures, appropriate crystallinity and optimal morphology are identified to be responsible for the observations. This rational multiphase composite strategy provides a promising idea for materials scientists to design and prepare scalable electrode materials for energy storage devices. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr08857g

Comprehensive computational design of ordered peptide macrocycles

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

Hosseinzadeh, Parisa; Bhardwaj, Gaurav; Mulligan, Vikram Khipple

Mixed chirality peptide macrocycles such as cyclosporine are among the most potent therapeutics identified to-date, but there is currently no way to systematically search through the structural space spanned by such compounds for new drug candidates. Natural proteins do not provide a useful guide: peptide macrocycles lack regular secondary structures and hydrophobic cores and have different backbone torsional constraints. Hence the development of new peptide macrocycles has been approached by modifying natural products or using library selection methods; the former is limited by the small number of known structures, and the latter by the limited size and diversity accessible throughmore » library-based methods. To overcome these limitations, here we enumerate the stable structures that can be adopted by macrocyclic peptides composed of L and D amino acids. We identify more than 200 designs predicted to fold into single stable structures, many times more than the number of currently available unbound peptide macrocycle structures. We synthesize and characterize by NMR twelve 7-10 residue macrocycles, 9 of which have structures very close to the design models in solution. NMR structures of three 11-14 residue bicyclic designs are also very close to the computational models. Our results provide a nearly complete coverage of the rich space of structures possible for short peptide based macrocycles unparalleled for other molecular systems, and vastly increase the available starting scaffolds for both rational drug design and library selection methods.« less

Comprehensive Optimization of LC-MS Metabolomics Methods Using Design of Experiments (COLMeD)

PubMed Central

Rhoades, Seth D.

2017-01-01

Introduction Both reverse-phase and HILIC chemistries are deployed for liquid-chromatography mass spectrometry (LC-MS) metabolomics analyses, however HILIC methods lag behind reverse-phase methods in reproducibility and versatility. Comprehensive metabolomics analysis is additionally complicated by the physiochemical diversity of metabolites and array of tunable analytical parameters. Objective Our aim was to rationally and efficiently design complementary HILIC-based polar metabolomics methods on multiple instruments using Design of Experiments (DoE). Methods We iteratively tuned LC and MS conditions on ion-switching triple quadrupole (QqQ) and quadrupole-time-of-flight (qTOF) mass spectrometers through multiple rounds of a workflow we term COLMeD (Comprehensive optimization of LC-MS metabolomics methods using design of experiments). Multivariate statistical analysis guided our decision process in the method optimizations. Results LC-MS/MS tuning for the QqQ method on serum metabolites yielded a median response increase of 161.5% (p<0.0001) over initial conditions with a 13.3% increase in metabolite coverage. The COLMeD output was benchmarked against two widely used polar metabolomics methods, demonstrating total ion current increases of 105.8% and 57.3%, with median metabolite response increases of 106.1% and 10.3% (p<0.0001 and p<0.05 respectively). For our optimized qTOF method, 22 solvent systems were compared on a standard mix of physiochemically diverse metabolites, followed by COLMeD optimization, yielding a median 29.8% response increase (p<0.0001) over initial conditions. Conclusions The COLMeD process elucidated response tradeoffs, facilitating improved chromatography and MS response without compromising separation of isobars. COLMeD is efficient, requiring no more than 20 injections in a given DoE round, and flexible, capable of class-specific optimization as demonstrated through acylcarnitine optimization within the QqQ method. PMID:28348510

Controlling the scattering properties of thin, particle-doped coatings

NASA Astrophysics Data System (ADS)

Rogers, William; Corbett, Madeleine; Manoharan, Vinothan

2013-03-01

Coatings and thin films of small particles suspended in a matrix possess optical properties that are important in several industries from cosmetics and paints to polymer composites. Many of the most interesting applications require coatings that produce several bulk effects simultaneously, but it is often difficult to rationally formulate materials with these desired optical properties. Here, we focus on the specific challenge of designing a thin colloidal film that maximizes both diffuse and total hemispherical transmission. We demonstrate that these bulk optical properties follow a simple scaling with two microscopic length scales: the scattering and transport mean free paths. Using these length scales and Mie scattering calculations, we generate basic design rules that relate scattering at the single particle level to the film's bulk optical properties. These ideas will be useful in the rational design of future optically active coatings.

Design for Additive Bio-Manufacturing: From Patient-Specific Medical Devices to Rationally Designed Meta-Biomaterials.

PubMed

Zadpoor, Amir A

2017-07-25

Recent advances in additive manufacturing (AM) techniques in terms of accuracy, reliability, the range of processable materials, and commercial availability have made them promising candidates for production of functional parts including those used in the biomedical industry. The complexity-for-free feature offered by AM means that very complex designs become feasible to manufacture, while batch-size-indifference enables fabrication of fully patient-specific medical devices. Design for AM (DfAM) approaches aim to fully utilize those features for development of medical devices with substantially enhanced performance and biomaterials with unprecedented combinations of favorable properties that originate from complex geometrical designs at the micro-scale. This paper reviews the most important approaches in DfAM particularly those applicable to additive bio-manufacturing including image-based design pipelines, parametric and non-parametric designs, metamaterials, rational and computationally enabled design, topology optimization, and bio-inspired design. Areas with limited research have been identified and suggestions have been made for future research. The paper concludes with a brief discussion on the practical aspects of DfAM and the potential of combining AM with subtractive and formative manufacturing processes in so-called hybrid manufacturing processes.

Design for Additive Bio-Manufacturing: From Patient-Specific Medical Devices to Rationally Designed Meta-Biomaterials

PubMed Central

Zadpoor, Amir A.

2017-01-01

Recent advances in additive manufacturing (AM) techniques in terms of accuracy, reliability, the range of processable materials, and commercial availability have made them promising candidates for production of functional parts including those used in the biomedical industry. The complexity-for-free feature offered by AM means that very complex designs become feasible to manufacture, while batch-size-indifference enables fabrication of fully patient-specific medical devices. Design for AM (DfAM) approaches aim to fully utilize those features for development of medical devices with substantially enhanced performance and biomaterials with unprecedented combinations of favorable properties that originate from complex geometrical designs at the micro-scale. This paper reviews the most important approaches in DfAM particularly those applicable to additive bio-manufacturing including image-based design pipelines, parametric and non-parametric designs, metamaterials, rational and computationally enabled design, topology optimization, and bio-inspired design. Areas with limited research have been identified and suggestions have been made for future research. The paper concludes with a brief discussion on the practical aspects of DfAM and the potential of combining AM with subtractive and formative manufacturing processes in so-called hybrid manufacturing processes. PMID:28757572

Rational and Experiential Decision-Making Preferences of Third-Year Student Pharmacists

PubMed Central

McLaughlin, Jacqueline E.; Cox, Wendy C.; Williams, Charlene R.

2014-01-01

Objective. To examine the rational (systematic and rule-based) and experiential (fast and intuitive) decision-making preferences of student pharmacists, and to compare these preferences to the preferences of other health professionals and student populations. Methods. The Rational-Experiential Inventory (REI-40), a validated psychometric tool, was administered electronically to 114 third-year (P3) student pharmacists. Student demographics and preadmission data were collected. The REI-40 results were compared with student demographics and admissions data to identify possible correlations between these factors. Results. Mean REI-40 rational scores were higher than experiential scores. Rational scores for younger students were significantly higher than students aged 30 years and older (p<0.05). No significant differences were found based on gender, race, or the presence of a prior degree. All correlations between REI-40 scores and incoming grade point average (GPA) and Pharmacy College Admission Test (PCAT) scores were weak. Conclusion. Student pharmacists favored rational decision making over experiential decision making, which was similar to results of studies done of other health professions. PMID:25147392

Fluid dynamic instabilities: theory and application to pattern forming in complex media

PubMed Central

Brun, P.-T.

2017-01-01

In this review article, we exemplify the use of stability analysis tools to rationalize pattern formation in complex media. Specifically, we focus on fluid flows, and show how the destabilization of their interface sets the blueprint of the patterns they eventually form. We review the potential use and limitations of the theoretical methods at the end, in terms of their applications to practical settings, e.g. as guidelines to design and fabricate structures while harnessing instabilities. This article is part of the themed issue ‘Patterning through instabilities in complex media: theory and applications’. PMID:28373378

Quantifying the process and outcomes of person-centered planning.

PubMed

Holburn, S; Jacobson, J W; Vietze, P M; Schwartz, A A; Sersen, E

2000-09-01

Although person-centered planning is a popular approach in the field of developmental disabilities, there has been little systematic assessment of its process and outcomes. To measure person-centered planning, we developed three instruments designed to assess its various aspects. We then constructed variables comprising both a Process and an Outcome Index using a combined rational-empirical method. Test-retest reliability and measures of internal consistency appeared adequate. Variable correlations and factor analysis were generally consistent with our conceptualization and resulting item and variable classifications. Practical implications for intervention integrity, program evaluation, and organizational performance are discussed.

Optimization of Typological Requirements for Low-Cost Detached Houses

NASA Astrophysics Data System (ADS)

Kuráň, Jozef

2017-09-01

The presented paper deals with an analysis of the legislative, hygienic, functional and operational requirements for the design of detached houses and individual dwellings in terms of typological requirements. The article also presents a sociological survey about the preferences and subjective requirements of relevant public group segments in terms of living in a detached house or an individual dwelling. The aim of the paper is to define the possibilities for the optimization of typological requirements. The optimization methods are based on principles already applied to contemporary detached house preferences and trends. The main idea is to reduce the amount of floor space, thus lowering construction and operating costs. The goal is to design an optimized floor plan, while preserving the hygienic criteria for individual residential dwellings. By applying optimization methods, a so-called rationalized and conditioned floor plan results in an individual dwelling floor plan design that can be compared to a reference model with an accurate quantification comparison. The significant sources of research are the legislative and normative requirements in the field of house construction in Slovakia, the Czech Republic and abroad.

Flux analysis and metabolomics for systematic metabolic engineering of microorganisms.

PubMed

Toya, Yoshihiro; Shimizu, Hiroshi

2013-11-01

Rational engineering of metabolism is important for bio-production using microorganisms. Metabolic design based on in silico simulations and experimental validation of the metabolic state in the engineered strain helps in accomplishing systematic metabolic engineering. Flux balance analysis (FBA) is a method for the prediction of metabolic phenotype, and many applications have been developed using FBA to design metabolic networks. Elementary mode analysis (EMA) and ensemble modeling techniques are also useful tools for in silico strain design. The metabolome and flux distribution of the metabolic pathways enable us to evaluate the metabolic state and provide useful clues to improve target productivity. Here, we reviewed several computational applications for metabolic engineering by using genome-scale metabolic models of microorganisms. We also discussed the recent progress made in the field of metabolomics and (13)C-metabolic flux analysis techniques, and reviewed these applications pertaining to bio-production development. Because these in silico or experimental approaches have their respective advantages and disadvantages, the combined usage of these methods is complementary and effective for metabolic engineering. Copyright © 2013 Elsevier Inc. All rights reserved.

Elucidating the druggable interface of protein-protein interactions using fragment docking and coevolutionary analysis.

PubMed

Bai, Fang; Morcos, Faruck; Cheng, Ryan R; Jiang, Hualiang; Onuchic, José N

2016-12-13

Protein-protein interactions play a central role in cellular function. Improving the understanding of complex formation has many practical applications, including the rational design of new therapeutic agents and the mechanisms governing signal transduction networks. The generally large, flat, and relatively featureless binding sites of protein complexes pose many challenges for drug design. Fragment docking and direct coupling analysis are used in an integrated computational method to estimate druggable protein-protein interfaces. (i) This method explores the binding of fragment-sized molecular probes on the protein surface using a molecular docking-based screen. (ii) The energetically favorable binding sites of the probes, called hot spots, are spatially clustered to map out candidate binding sites on the protein surface. (iii) A coevolution-based interface interaction score is used to discriminate between different candidate binding sites, yielding potential interfacial targets for therapeutic drug design. This approach is validated for important, well-studied disease-related proteins with known pharmaceutical targets, and also identifies targets that have yet to be studied. Moreover, therapeutic agents are proposed by chemically connecting the fragments that are strongly bound to the hot spots.

Self-assembly of multi-stranded RNA motifs into lattices and tubular structures

DOE PAGES

Stewart, Jaimie Marie; Subramanian, Hari K. K.; Franco, Elisa

2017-02-16

Rational design of nucleic acidmolecules yields selfassembling scaffolds with increasing complexity, size and functionality. It is an open question whether design methods tailored to build DNA nanostructures can be adapted to build RNA nanostructures with comparable features. We demonstrate the formation of RNA lattices and tubular assemblies from double crossover (DX) tiles, a canonical motif in DNA nanotechnology. Tubular structures can exceed 1 m in length, suggesting that this DX motif can produce very robust lattices. Some of these tubes spontaneously form with left-handed chirality. We obtain assemblies by using two methods: a protocol where gel-extracted RNA strands are slowlymore » annealed, and a one-pot transcription and anneal procedure. We then identify the tile nick position as a structural requirement for lattice formation. These results demonstrate that stable RNA structures can be obtained with design tools imported from DNA nanotechnology. These large assemblies could be potentially integrated with a variety of functional RNA motifs for drug or nanoparticle delivery, or for colocalization of cellular components.« less

Self-assembly of multi-stranded RNA motifs into lattices and tubular structures

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

Stewart, Jaimie Marie; Subramanian, Hari K. K.; Franco, Elisa

Rational design of nucleic acidmolecules yields selfassembling scaffolds with increasing complexity, size and functionality. It is an open question whether design methods tailored to build DNA nanostructures can be adapted to build RNA nanostructures with comparable features. We demonstrate the formation of RNA lattices and tubular assemblies from double crossover (DX) tiles, a canonical motif in DNA nanotechnology. Tubular structures can exceed 1 m in length, suggesting that this DX motif can produce very robust lattices. Some of these tubes spontaneously form with left-handed chirality. We obtain assemblies by using two methods: a protocol where gel-extracted RNA strands are slowlymore » annealed, and a one-pot transcription and anneal procedure. We then identify the tile nick position as a structural requirement for lattice formation. These results demonstrate that stable RNA structures can be obtained with design tools imported from DNA nanotechnology. These large assemblies could be potentially integrated with a variety of functional RNA motifs for drug or nanoparticle delivery, or for colocalization of cellular components.« less

Fixing Stellarator Magnetic Surfaces

NASA Astrophysics Data System (ADS)

Hanson, James D.

1999-11-01

Magnetic surfaces are a perennial issue for stellarators. The design heuristic of finding a magnetic field with zero perpendicular component on a specified outer surface often yields inner magnetic surfaces with very small resonant islands. However, magnetic fields in the laboratory are not design fields. Island-causing errors can arise from coil placement errors, stray external fields, and design inadequacies such as ignoring coil leads and incomplete characterization of current distributions within the coil pack. The problem addressed is how to eliminate such error-caused islands. I take a perturbation approach, where the zero order field is assumed to have good magnetic surfaces, and comes from a VMEC equilibrium. The perturbation field consists of error and correction pieces. The error correction method is to determine the correction field so that the sum of the error and correction fields gives zero island size at specified rational surfaces. It is particularly important to correctly calculate the island size for a given perturbation field. The method works well with many correction knobs, and a Singular Value Decomposition (SVD) technique is used to determine minimal corrections necessary to eliminate islands.

Self-assembly of multi-stranded RNA motifs into lattices and tubular structures

PubMed Central

Stewart, Jaimie Marie; Subramanian, Hari K. K.

2017-01-01

Abstract Rational design of nucleic acid molecules yields self-assembling scaffolds with increasing complexity, size and functionality. It is an open question whether design methods tailored to build DNA nanostructures can be adapted to build RNA nanostructures with comparable features. Here we demonstrate the formation of RNA lattices and tubular assemblies from double crossover (DX) tiles, a canonical motif in DNA nanotechnology. Tubular structures can exceed 1 μm in length, suggesting that this DX motif can produce very robust lattices. Some of these tubes spontaneously form with left-handed chirality. We obtain assemblies by using two methods: a protocol where gel-extracted RNA strands are slowly annealed, and a one-pot transcription and anneal procedure. We identify the tile nick position as a structural requirement for lattice formation. Our results demonstrate that stable RNA structures can be obtained with design tools imported from DNA nanotechnology. These large assemblies could be potentially integrated with a variety of functional RNA motifs for drug or nanoparticle delivery, or for colocalization of cellular components. PMID:28204562

Green chemistry for nanoparticle synthesis.

PubMed

Duan, Haohong; Wang, Dingsheng; Li, Yadong

2015-08-21

The application of the twelve principles of green chemistry in nanoparticle synthesis is a relatively new emerging issue concerning the sustainability. This field has received great attention in recent years due to its capability to design alternative, safer, energy efficient, and less toxic routes towards synthesis. These routes have been associated with the rational utilization of various substances in the nanoparticle preparations and synthetic methods, which have been broadly discussed in this tutorial review. This article is not meant to provide an exhaustive overview of green synthesis of nanoparticles, but to present several pivotal aspects of synthesis with environmental concerns, involving the selection and evaluation of nontoxic capping and reducing agents, the choice of innocuous solvents and the development of energy-efficient synthetic methods.

The pseudo-Boolean optimization approach to form the N-version software structure

NASA Astrophysics Data System (ADS)

Kovalev, I. V.; Kovalev, D. I.; Zelenkov, P. V.; Voroshilova, A. A.

2015-10-01

The problem of developing an optimal structure of N-version software system presents a kind of very complex optimization problem. This causes the use of deterministic optimization methods inappropriate for solving the stated problem. In this view, exploiting heuristic strategies looks more rational. In the field of pseudo-Boolean optimization theory, the so called method of varied probabilities (MVP) has been developed to solve problems with a large dimensionality. Some additional modifications of MVP have been made to solve the problem of N-version systems design. Those algorithms take into account the discovered specific features of the objective function. The practical experiments have shown the advantage of using these algorithm modifications because of reducing a search space.

Effect of processing on Polymer/Composite structure and properties

NASA Technical Reports Server (NTRS)

1982-01-01

Advances in the vitality and economic health of the field of polymer forecasting are discussed. A consistent and rational point of view which considers processing as a participant in the underlying triad of relationships which comprise materials science and engineering is outlined. This triad includes processing as it influences material structure, and ultimately properties. Methods in processing structure properties, polymer science and engineering, polymer chemistry and synthesis, structure and modification and optimization through processing, and methods of melt flow modeling in processing structure property relations of polymer were developed. Mechanical properties of composites are considered, and biomedical materials research to include polymer processing effects are studied. An analysis of the design technology of advances graphite/epoxy composites is also reported.

The Rational Patient and Beyond: Implications for Treatment Adherence in People with Psychiatric Disabilities

PubMed Central

Corrigan, Patrick W.; Rüsch, Nicolas; Ben-Zeev, Dror; Sher, Tamara

2014-01-01

Purpose/Objective Many people with psychiatric disabilities do not benefit from evidence-based practices because they often do not seek out or fully adhere to them. One way psychologists have made sense of this rehabilitation and health decision process and subsequent behaviors (of which adherence might be viewed as one) is by proposing a “rational patient;” namely, that decisions are made deliberatively by weighing perceived costs and benefits of intervention options. Social psychological research, however, suggests limitations to a rational patient theory that impact models of health decision making. Design The research literature was reviewed for studies of rational patient models and alternative theories with empirical support. Special focus was on models specifically related to decisions about rehabilitation strategies for psychiatric disability. Results Notions of the rational patient evolved out of several psychological models including the health belief model, protection motivation theory, and theory of planned behavior. A variety of practice strategies evolved to promote rational decision making. However, research also suggests limitations to rational deliberations of health. (1) Rather than carefully and consciously considered, many health decisions are implicit, potentially occurring outside awareness. (2) Decisions are not always planful; often it is the immediate exigencies of a context rather than an earlier balance of costs and benefits that has the greatest effects. (3) Cool cognitions often do not dictate the process; emotional factors have an important role in health decisions. Each of these limitations suggests additional practice strategies that facilitate a person’s health decisions. Conclusions/Implications Old models of rational decision making need to be supplanted by multi-process models that explain supra-deliberative factors in health decisions and behaviors. PMID:24446671

Rational design of metal nitride redox materials for solar-driven ammonia synthesis.

PubMed

Michalsky, Ronald; Pfromm, Peter H; Steinfeld, Aldo

2015-06-06

Fixed nitrogen is an essential chemical building block for plant and animal protein, which makes ammonia (NH3) a central component of synthetic fertilizer for the global production of food and biofuels. A global project on artificial photosynthesis may foster the development of production technologies for renewable NH3 fertilizer, hydrogen carrier and combustion fuel. This article presents an alternative path for the production of NH3 from nitrogen, water and solar energy. The process is based on a thermochemical redox cycle driven by concentrated solar process heat at 700-1200°C that yields NH3 via the oxidation of a metal nitride with water. The metal nitride is recycled via solar-driven reduction of the oxidized redox material with nitrogen at atmospheric pressure. We employ electronic structure theory for the rational high-throughput design of novel metal nitride redox materials and to show how transition-metal doping controls the formation and consumption of nitrogen vacancies in metal nitrides. We confirm experimentally that iron doping of manganese nitride increases the concentration of nitrogen vacancies compared with no doping. The experiments are rationalized through the average energy of the dopant d-states, a descriptor for the theory-based design of advanced metal nitride redox materials to produce sustainable solar thermochemical ammonia.

Rational design of metal nitride redox materials for solar-driven ammonia synthesis

PubMed Central

Michalsky, Ronald; Pfromm, Peter H.; Steinfeld, Aldo

2015-01-01

Fixed nitrogen is an essential chemical building block for plant and animal protein, which makes ammonia (NH3) a central component of synthetic fertilizer for the global production of food and biofuels. A global project on artificial photosynthesis may foster the development of production technologies for renewable NH3 fertilizer, hydrogen carrier and combustion fuel. This article presents an alternative path for the production of NH3 from nitrogen, water and solar energy. The process is based on a thermochemical redox cycle driven by concentrated solar process heat at 700–1200°C that yields NH3 via the oxidation of a metal nitride with water. The metal nitride is recycled via solar-driven reduction of the oxidized redox material with nitrogen at atmospheric pressure. We employ electronic structure theory for the rational high-throughput design of novel metal nitride redox materials and to show how transition-metal doping controls the formation and consumption of nitrogen vacancies in metal nitrides. We confirm experimentally that iron doping of manganese nitride increases the concentration of nitrogen vacancies compared with no doping. The experiments are rationalized through the average energy of the dopant d-states, a descriptor for the theory-based design of advanced metal nitride redox materials to produce sustainable solar thermochemical ammonia. PMID:26052421

Rational design and application of responsive alpha-helical peptide hydrogels.

PubMed

Banwell, Eleanor F; Abelardo, Edgardo S; Adams, Dave J; Birchall, Martin A; Corrigan, Adam; Donald, Athene M; Kirkland, Mark; Serpell, Louise C; Butler, Michael F; Woolfson, Derek N

2009-07-01

Biocompatible hydrogels have a wide variety of potential applications in biotechnology and medicine, such as the controlled delivery and release of cells, cosmetics and drugs, and as supports for cell growth and tissue engineering. Rational peptide design and engineering are emerging as promising new routes to such functional biomaterials. Here, we present the first examples of rationally designed and fully characterized self-assembling hydrogels based on standard linear peptides with purely alpha-helical structures, which we call hydrogelating self-assembling fibres (hSAFs). These form spanning networks of alpha-helical fibrils that interact to give self-supporting physical hydrogels of >99% water content. The peptide sequences can be engineered to alter the underlying mechanism of gelation and, consequently, the hydrogel properties. Interestingly, for example, those with hydrogen-bonded networks of fibrils melt on heating, whereas those formed through hydrophobic fibril-fibril interactions strengthen when warmed. The hSAFs are dual-peptide systems that gel only on mixing, which gives tight control over assembly. These properties raise possibilities for using the hSAFs as substrates in cell culture. We have tested this in comparison with the widely used Matrigel substrate, and demonstrate that, like Matrigel, hSAFs support both growth and differentiation of rat adrenal pheochromocytoma cells for sustained periods in culture.

Rational design and application of responsive α-helical peptide hydrogels

PubMed Central

Banwell, Eleanor F.; Abelardo, Edgardo S.; Adams, Dave J.; Birchall, Martin A.; Corrigan, Adam; Donald, Athene M.; Kirkland, Mark; Serpell, Louise C.; Butler, Michael F.; Woolfson, Derek N.

2009-01-01

Biocompatible hydrogels have a wide variety of potential applications in biotechnology and medicine, such as the controlled delivery and release of cells, cosmetics and drugs; and as supports for cell growth and tissue engineering1. Rational peptide design and engineering are emerging as promising new routes to such functional biomaterials2-4. Here we present the first examples of rationally designed and fully characterized self-assembling hydrogels based on standard linear peptides with purely α-helical structures, which we call hydrogelating self-assembling fibres (hSAFs). These form spanning networks of α-helical fibrils that interact to give self-supporting physical hydrogels of >99% water content. The peptide sequences can be engineered to alter the underlying mechanism of gelation and, consequently, the hydrogel properties. Interestingly, for example, those with hydrogen-bonded networks melt upon heating, whereas those formed via hydrophobic interactions strengthen when warmed. The hSAFs are dual-peptide systems that only gel on mixing, which gives tight control over assembly5. These properties raise possibilities for using the hSAFs as substrates in cell culture. We have tested this in comparison with the widely used Matrigel substrate, and demonstrate that, like Matrigel, hSAFs support both growth and differentiation of rat adrenal pheochromocytoma cells for sustained periods in culture. PMID:19543314

Rational design and application of responsive α-helical peptide hydrogels

NASA Astrophysics Data System (ADS)

Banwell, Eleanor F.; Abelardo, Edgardo S.; Adams, Dave J.; Birchall, Martin A.; Corrigan, Adam; Donald, Athene M.; Kirkland, Mark; Serpell, Louise C.; Butler, Michael F.; Woolfson, Derek N.

2009-07-01

Biocompatible hydrogels have a wide variety of potential applications in biotechnology and medicine, such as the controlled delivery and release of cells, cosmetics and drugs, and as supports for cell growth and tissue engineering. Rational peptide design and engineering are emerging as promising new routes to such functional biomaterials. Here, we present the first examples of rationally designed and fully characterized self-assembling hydrogels based on standard linear peptides with purely α-helical structures, which we call hydrogelating self-assembling fibres (hSAFs). These form spanning networks of α-helical fibrils that interact to give self-supporting physical hydrogels of >99% water content. The peptide sequences can be engineered to alter the underlying mechanism of gelation and, consequently, the hydrogel properties. Interestingly, for example, those with hydrogen-bonded networks of fibrils melt on heating, whereas those formed through hydrophobic fibril-fibril interactions strengthen when warmed. The hSAFs are dual-peptide systems that gel only on mixing, which gives tight control over assembly. These properties raise possibilities for using the hSAFs as substrates in cell culture. We have tested this in comparison with the widely used Matrigel substrate, and demonstrate that, like Matrigel, hSAFs support both growth and differentiation of rat adrenal pheochromocytoma cells for sustained periods in culture.

A design of high-precision BLDCM drive with bus voltage protection

NASA Astrophysics Data System (ADS)

Lian, Xuezheng; Wang, Haitao; Xie, Meilin; Huang, Wei; Li, Dawei; Jing, Feng

2017-11-01

In the application of space satellite turntable, the design of balance wheel is very necessary. To solve the acquisition precision of Brushless DC motor speed is low, and the encoder is also more complex, this paper improves the original hall signal measurement methods. Using the logic device to achieve the six frequency multiplication of hall signal, the signal is used as speed feedback to achieve speed closed-loop control and improve the speed stability. At the same time, in order to prevent the E.M.F of BLDC motor to raise the voltage of the bus bar when reversing or braking, and affect the normal operation of other circuit modules, the analog circuit is used to protect the bus bar voltage by the way of energy consumption braking. The experimental results are consistent with the theoretical design, and the rationality and feasibility of the frequency multiplication scheme and bus voltage protection scheme are verified.

Precise Design of Phosphorescent Molecular Butterflies with Tunable Photoinduced Structural Change and Dual Emission.

PubMed

Zhou, Chenkun; Tian, Yu; Yuan, Zhao; Han, Mingu; Wang, Jamie; Zhu, Lei; Tameh, Maliheh Shaban; Huang, Chen; Ma, Biwu

2015-08-10

Photoinduced structural change (PSC) is a fundamental excited-state dynamic process in chemical and biological systems. However, precise control of PSC processes is very challenging, owing to the lack of guidelines for designing excited-state potential energy surfaces (PESs). A series of rationally designed butterfly-like phosphorescent binuclear platinum complexes that undergo controlled PSC by Pt-Pt distance shortening and exhibit tunable dual (greenish-blue and red) emission are herein reported. Based on the Bell-Evans-Polanyi principle, it is demonstrated how the energy barrier of the PSC, which can be described as a chemical-reaction-like process between the two energy minima on the first triplet excited-state PES, can be controlled by synthetic means. These results reveal a simple method to engineer the dual emission of molecular systems by manipulating PES to control PSC. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Approximate techniques of structural reanalysis

NASA Technical Reports Server (NTRS)

Noor, A. K.; Lowder, H. E.

1974-01-01

A study is made of two approximate techniques for structural reanalysis. These include Taylor series expansions for response variables in terms of design variables and the reduced-basis method. In addition, modifications to these techniques are proposed to overcome some of their major drawbacks. The modifications include a rational approach to the selection of the reduced-basis vectors and the use of Taylor series approximation in an iterative process. For the reduced basis a normalized set of vectors is chosen which consists of the original analyzed design and the first-order sensitivity analysis vectors. The use of the Taylor series approximation as a first (initial) estimate in an iterative process, can lead to significant improvements in accuracy, even with one iteration cycle. Therefore, the range of applicability of the reanalysis technique can be extended. Numerical examples are presented which demonstrate the gain in accuracy obtained by using the proposed modification techniques, for a wide range of variations in the design variables.

Algebraic grid adaptation method using non-uniform rational B-spline surface modeling

NASA Technical Reports Server (NTRS)

Yang, Jiann-Cherng; Soni, B. K.

1992-01-01

An algebraic adaptive grid system based on equidistribution law and utilized by the Non-Uniform Rational B-Spline (NURBS) surface for redistribution is presented. A weight function, utilizing a properly weighted boolean sum of various flow field characteristics is developed. Computational examples are presented to demonstrate the success of this technique.

Utility, Economic Rationalism and the Circumscription of Agency

ERIC Educational Resources Information Center

Dirita, P. A.; Parmenter, T. R.; Stancliffe, R. J.

2008-01-01

Background: Great strides have been achieved over the past few decades in service provision for people with intellectual disability (ID). However, there has also been a growth in the use of economic rationalism and a related rise in managerialism in forming service provision outcomes. Method: An account of the focus on process and means of…

Comparison of Cue-Controlled Desensitization, Rational Restructuring, and a Credible Placebo in the Treatment of Speech Anxiety.

ERIC Educational Resources Information Center

Lent, Robert W.; And Others

1981-01-01

The efficacy of cue-controlled desensitization and systematic rational restructuring was compared with a placebo method and a waiting-list control in reducing public speaking and nontargeted anxieties. Cue-controlled desensitization was generally more effective than the other groups in reducing subjective speech anxiety. (Author)

An Intricate Fabric: Understanding the Rationality of Practice

ERIC Educational Resources Information Center

Dunne, Joseph

2005-01-01

This article provides an account of a "neo-Aristotelian" conception of practice. It introduces this account through an analysis of internal and external goods of practices. It then delineates a crucial distinction between practical and technical rationality and grounds this distinction in an analysis of the priority of "material" over "method" in…

Nisin Migration in Shelf Stable, Tuna-Filled Tortillas During Storage

DTIC Science & Technology

2014-09-22

RATIONS SHELF LIFE ACCEPTABILITY MICROCOCCUS LUTEUS STORAGE INHIBITION MILITARY RATIONS...7 Figure 3. The assay of nisin against Micrococcus luteus ATCC 10240 in tuna enrobed in a tortilla wrap...METHODS 2.1 BACTERIAL STRAINS, MEDIA, AND BUFFER The nisin-sensitive test organism, Micrococcus luteus ATCC® 10240, was obtained from the American

75 FR 80765 - Hazardous Materials: Adoption of ASME Code Section XII and the National Board Inspection Code

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-23

... requirement for allowable peak secondary stresses for MC 331 cargo tanks. 4. Rational Design of Non-circular... the design, construction, and certification of cargo tank motor vehicles, cryogenic portable tanks and... CTMV: Cargo Tank Motor Vehicle DCE: Design Certifying Engineer FMCSA: Federal Motor Carrier Safety...

Project-Based Pedagogy for the Facilitation of Webpage Design

ERIC Educational Resources Information Center

Jakovljevic, Maria; Ankiewicz, Piet

2016-01-01

Real issues of web design and development include many problem-solving tasks. There are, however, some inadequacies associated with the implementation of appropriate pedagogy for organised and structured instruction that supports the rational problem-solving paradigm. The purpose of this article is to report on a study for the design and…

Developing a (Non-Linear) Practice of Design Thinking

ERIC Educational Resources Information Center

Teal, Randall

2010-01-01

Design thinking can be a powerful way to engage the world, allowing interactive understandings that are both analytic and experiential. When fully functioning, design thinking necessarily calls upon faculties often considered a-rational, a-causal and a-logical. Unfortunately, such faculties often give rise to academic suspicion. That is to say,…

[Rational bases for cooperation between epidemiologists and mathematicians].

PubMed

Favorova, L A; Shatrov, I I

1977-10-01

The authors consider rational foundations underlying creatin of realistic models. The principal condition for the successful mathematical modelling is obtaining of the most full value primary materials on the course of the epidemic process. For this purpose the authors suggest definite principles of the methodical approach to the mathematical modelling. Possibilities of the use of mathematical methods for various groups of infections are consideder. Particular attention is paid to the works on the study of the infection risk in "small" collective bodies.

Comprehensive Optimization of LC-MS Metabolomics Methods Using Design of Experiments (COLMeD).

PubMed

Rhoades, Seth D; Weljie, Aalim M

2016-12-01

Both reverse-phase and HILIC chemistries are deployed for liquid-chromatography mass spectrometry (LC-MS) metabolomics analyses, however HILIC methods lag behind reverse-phase methods in reproducibility and versatility. Comprehensive metabolomics analysis is additionally complicated by the physiochemical diversity of metabolites and array of tunable analytical parameters. Our aim was to rationally and efficiently design complementary HILIC-based polar metabolomics methods on multiple instruments using Design of Experiments (DoE). We iteratively tuned LC and MS conditions on ion-switching triple quadrupole (QqQ) and quadrupole-time-of-flight (qTOF) mass spectrometers through multiple rounds of a workflow we term COLMeD (Comprehensive optimization of LC-MS metabolomics methods using design of experiments). Multivariate statistical analysis guided our decision process in the method optimizations. LC-MS/MS tuning for the QqQ method on serum metabolites yielded a median response increase of 161.5% (p<0.0001) over initial conditions with a 13.3% increase in metabolite coverage. The COLMeD output was benchmarked against two widely used polar metabolomics methods, demonstrating total ion current increases of 105.8% and 57.3%, with median metabolite response increases of 106.1% and 10.3% (p<0.0001 and p<0.05 respectively). For our optimized qTOF method, 22 solvent systems were compared on a standard mix of physiochemically diverse metabolites, followed by COLMeD optimization, yielding a median 29.8% response increase (p<0.0001) over initial conditions. The COLMeD process elucidated response tradeoffs, facilitating improved chromatography and MS response without compromising separation of isobars. COLMeD is efficient, requiring no more than 20 injections in a given DoE round, and flexible, capable of class-specific optimization as demonstrated through acylcarnitine optimization within the QqQ method.

The Special Education Teacher as an Instructional Designer. Rational, Content, and Strategy for an Innovative Individualized Course on Instructional Design in Special Education. Working Paper 9.14.

ERIC Educational Resources Information Center

Thiagarajan, Sivasailam

Provided are the rationale, content and strategy for an introductory course in instructional design for special education teachers. The teacher's need for varied competencies in instructional design, management and interaction are discussed. It is recommended that teacher training include development of such design skills as task analysis, learner…

Rational Discovery of (+) (S) Abscisic Acid as a Potential Antifungal Agent: a Repurposing Approach.

PubMed

Khedr, Mohammed A; Massarotti, Alberto; Mohamed, Maged E

2018-06-04

Fungal infections are spreading widely worldwide, and the types of treatment are limited due to the lack of diverse therapeutic agents and their associated side effects and toxicity. The discovery of new antifungal classes is vital and critical. We discovered the antifungal activity of abscisic acid through a rational drug design methodology that included the building of homology models for fungal chorismate mutases and a pharmacophore model derived from a transition state inhibitor. Ligand-based virtual screening resulted in some hits that were filtered using molecular docking and molecular dynamic simulations studies. Both in silico methods and in vitro antifungal assays were used as tools to select and validate the abscisic acid repurposing. Abscisic acid inhibition assays confirmed the inhibitory effect of abscisic acid on chorismate mutase through the inhibition of phenylpyruvate production. The repositioning of abscisic acid, the well-known and naturally occurring plant growth regulator, as a potential antifungal agent because of its suggested action as an inhibitor to several fungal chorismate mutases was the main result of this work.

Effects of a rational-emotive health education intervention on stress management and irrational beliefs among technical college teachers in Southeast Nigeria

PubMed Central

Ugwoke, Samuel C.; Eseadi, Chiedu; Igbokwe, Chima C.; Chiaha, Gertrude T.U.; Nwaubani, Okechukwu O.; Orji, Chibueze Tobias; Ugwuanyi, Leonard T.; Chukwuma, Ifeoma S.; Edikpa, Edith C.; Ogakwu, Vera N.; Onu, Eucharia A.; Agu, Patricia; Nwobi, Ujunwa A.; Omeke, Faith; Okeke, Francisca C.; Ezema, Rita N.; Abugu, Lawretta I.

2017-01-01

Abstract Background: Stress is the product of how an individual reacts and adapts to the specific demands and threats they encounter while carrying out given tasks. The main purpose of this study was to investigate the effects of a rational-emotive health education intervention (REHEI) on stress management, and irrational beliefs in a sample of technical college teachers in Southeast Nigeria. Method: The study design was a pretest–posttest control group. Repeated measures analysis of variance, paired t test and Mann–Whitney U tests were used to analyze the data collected. Results: The REHEI significantly reduced teacher stress in those teaching staff exposed to the treatment intervention, relative to a waitlist control group. Furthermore, the REHEI program significantly decreased irrational beliefs about teaching in those teaching staff exposed to the treatment intervention compared to a waitlist control group. Conclusion: The REHEI program can be used to coach teachers on how to manage and cope with stress and overcome irrational beliefs in teaching. PMID:28767584

Experimental Investigation of a Temperature-Controlled Car Seat Powered by an Exhaust Thermoelectric Generator

NASA Astrophysics Data System (ADS)

Du, H.; Wang, Y. P.; Yuan, X. H.; Deng, Y. D.; Su, C. Q.

2016-03-01

To improve the riding comfort and rational utilization of the electrical energy captured by an automotive thermoelectric generator (ATEG), a temperature-controlled car seat was constructed to adjust the temperature of the car seat surface. Powered by the ATEG and the battery, the seat-embedded air conditioner can improve the riding comfort using a thermoelectric device to adjust the surface temperature of the seat, with an air duct to regulate the cold side and hot side of the thermoelectric device. The performance of the thermoelectric cooler (TEC) and theoretical analysis on the optimum state of the TEC device are put forward. To verify the rationality of the air duct design and to ensure sufficient air supply, the velocity field of the air duct system was obtained by means of the finite element method. To validate the reliability of the numerical simulation, the air velocity around the thermoelectric device was measured by a wind speed transmitter. The performance of the temperature-controlled car seat has been validated and is in good agreement with bench tests and real vehicle tests.

[Assessment of dietary habits in students of the Medical University of Bialystok with differentiated nutritional status].

PubMed

Stefańiska, Ewa; Ostrowska, Lucyna; Sajewicz, Joanna

2011-01-01

The research was conducted into 360 students of Medical University in Bialystok with differentiated nutritional status. The study involved 251 female students (46 with underweight, 186 with normal weight, 19 with excessive body weight) and 69 male students (7 with underweight, 47 with normal weight, 15 with excessive body weight). The quantity analyze of daily food rations was conducted on the base of the previous day 24 h dietary recall method. The computer program Diet 2.0 designed in the Institute of Food and Nutrition in Warsaw was used for calculations. Energetic value and basic nutrients supply was estimated and also the average content of dietary fiber and cholesterol. The results of the conducted research indicate lack ofbalanced content ofessential nutrients in daily food rations of the tested students of both sexes, irrespective of nutritional status. Energy supply was far too low comparing to recommended standards. It was proved that carbohydrate and fat supply was definitely lower than recommended standards. The research also showed low consumption of dietary fiber in all investigated groups and high consumption of cholesterol in men.

Synthetic Biological Approaches to Natural Product Biosynthesis

PubMed Central

Winter, Jaclyn M; Tang, Yi

2012-01-01

Small molecules produced in Nature continue to be an inspiration for the development of new therapeutic agents. These natural products possess exquisite chemical diversity, which gives rise to their wide range of biological activities. In their host organism, natural products are assembled and modified by dedicated biosynthetic pathways that Nature has meticulously developed. Often times, the complex structures or chemical modifications instated by these pathways are difficult to replicate using traditional synthetic methods. An alternative approach for creating or enhancing the structural variation of natural products is through combinatorial biosynthesis. By rationally reprogramming and manipulating the biosynthetic machinery responsible for their production, unnatural metabolites that were otherwise inaccessible can be obtained. Additionally, new chemical structures can be synthesized or derivatized by developing the enzymes that carry out these complicated chemical reactions into biocatalysts. In this review, we will discuss a variety of combinatorial biosynthetic strategies, their technical challenges, and highlight some recent (since 2007) examples of rationally designed unnatural metabolites, as well as platforms that have been established for the production and modification of clinically important pharmaceutical compounds. PMID:22221832

Rational Synthesis of Hollow Prussian Blue Analogue Through Coordination Replication and Controlled-Etching for Cs-Ion Removal.

PubMed

Xu, Jun; Bu, Fan-Xing; Guo, Yi-Fei; Zhang, Wei; Hu, Ming; Jiang, Ji-Sen

2018-05-01

Radioactive cesium pollution have received considerable attention due to the increasing risks in development of the nuclear power plants in the world. Although various functional porous materials are utilized to adsorb Cs+ ions in water, Prussian blue analogues (PBAs) are an impressive class of candidates because of their super affinity of Cs+ ions. The adsorption ability of the PBAs strongly relate to the mesostructure and interstitial sites. To design a hollow PBA with large number of interstitial sites, the traditional hollowing methods are not suitable owing to the difficulty in processing the specific PBAs with large number of interstitial sites. In this work, we empolyed a rational strategy which was to form a "metal oxide"@"PBA" core-shell structure via coordination replication at first, then utilized a mild etching to remove the metal oxide core, led to hollow PBA finally. The obtained hollow PBAs were of high crystallinity and large number of interstitial sites, showing a super adsorption performance for Cs+ ions (221.6 mg/g) within a short period (10 min).

Measuring Resilience.

PubMed

Hoffman, Robert R; Hancock, P A

2017-06-01

As human factors and ergonomics (HF/E) moves to embrace a greater systems perspective concerning human-machine technologies, new and emergent properties, such as resilience, have arisen. Our objective here is to promote discussion as to how to measure this latter, complex phenomenon. Resilience is now a much-referenced goal for technology and work system design. It subsumes the new movement of resilience engineering. As part of a broader systems approach to HF/E, this concept requires both a definitive specification and an associated measurement methodology. Such an effort epitomizes our present work. Using rational analytic and synthetic methods, we offer an approach to the measurement of resilience capacity. We explicate how our proposed approach can be employed to compare resilience across multiple systems and domains, and emphasize avenues for its future development and validation. Emerging concerns for the promise and potential of resilience and associated concepts, such as adaptability, are highlighted. Arguments skeptical of these emerging dimensions must be met with quantitative answers; we advance one approach here. Robust and validated measures of resilience will enable coherent and rational discussions of complex emergent properties in macrocognitive system science.

Two-color SERS microscopy for protein co-localization in prostate tissue with primary antibody-protein A/G-gold nanocluster conjugates

NASA Astrophysics Data System (ADS)

Salehi, Mohammad; Schneider, Lilli; Ströbel, Philipp; Marx, Alexander; Packeisen, Jens; Schlücker, Sebastian

2014-01-01

SERS microscopy is a novel staining technique in immunohistochemistry, which is based on antibodies labeled with functionalized noble metal colloids called SERS labels or nanotags for optical detection. Conventional covalent bioconjugation of these SERS labels cannot prevent blocking of the antigen recognition sites of the antibody. We present a rational chemical design for SERS label-antibody conjugates which addresses this issue. Highly sensitive, silica-coated gold nanoparticle clusters as SERS labels are non-covalently conjugated to primary antibodies by using the chimeric protein A/G, which selectively recognizes the Fc part of antibodies and therefore prevents blocking of the antigen recognition sites. In proof-of-concept two-color imaging experiments for the co-localization of p63 and PSA on non-neoplastic prostate tissue FFPE specimens, we demonstrate the specificity and signal brightness of these rationally designed primary antibody-protein A/G-gold nanocluster conjugates.SERS microscopy is a novel staining technique in immunohistochemistry, which is based on antibodies labeled with functionalized noble metal colloids called SERS labels or nanotags for optical detection. Conventional covalent bioconjugation of these SERS labels cannot prevent blocking of the antigen recognition sites of the antibody. We present a rational chemical design for SERS label-antibody conjugates which addresses this issue. Highly sensitive, silica-coated gold nanoparticle clusters as SERS labels are non-covalently conjugated to primary antibodies by using the chimeric protein A/G, which selectively recognizes the Fc part of antibodies and therefore prevents blocking of the antigen recognition sites. In proof-of-concept two-color imaging experiments for the co-localization of p63 and PSA on non-neoplastic prostate tissue FFPE specimens, we demonstrate the specificity and signal brightness of these rationally designed primary antibody-protein A/G-gold nanocluster conjugates. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr05890e

The equivalence of a human observer and an ideal observer in binary diagnostic tasks

NASA Astrophysics Data System (ADS)

He, Xin; Samuelson, Frank; Gallas, Brandon D.; Sahiner, Berkman; Myers, Kyle

2013-03-01

The Ideal Observer (IO) is "ideal" for given data populations. In the image perception process, as the raw images are degraded by factors such as display and eye optics, there is an equivalent IO (EIO). The EIO uses the statistical information that exits the perception/cognitive degradations as the data. We assume a human observer who received sufficient training, e.g., radiologists, and hypothesize that such a human observer can be modeled as if he is an EIO. To measure the likelihood ratio (LR) distributions of an EIO, we formalize experimental design principles that encourage rationality based on von Neumann and Morgenstern's (vNM) axioms. We present examples to show that many observer study design refinements, although motivated by empirical principles explicitly, implicitly encourage rationality. Our hypothesis is supported by a recent review paper on ROC curve convexity by Pesce, Metz, and Berbaum. We also provide additional evidence based on a collection of observer studies in medical imaging. EIO theory shows that the "sub-optimal" performance of a human observer can be mathematically formalized in the form of an IO, and measured through rationality encouragement.

Nano-array based monolithic catalysts: Concept, rational materials design and tunable catalytic performance

DOE PAGES

Ren, Zheng; Guo, Yanbing; Gao, Pu-Xian

2015-03-20

Monolithic catalysts, also known as structured catalysts, represent an important catalyst configuration widely used in automotive, chemical, and energy industries. However, several issues associated with washcoat based monolithic catalyst preparation are ever present, such as compromised materials utilization efficiency due to a less-than-ideal wash coating process, difficulty in precise and optimum microstructure control and lack of structure-property correlation. Here, in this mini-review, we introduce the concept of nano-array catalyst, a new type of monolithic catalyst featuring high catalyst utilization efficiency, good thermal/mechanical robustness, and catalytic performance tunability. A comprehensive overview is presented with detailed discussion of the strategies for nano-arraymore » catalyst preparation and rational catalytic activity adjustment enabled by the well-defined nano-array geometry. Specifically their scalable fabrication processes are reviewed in conjunction with discussion of their various catalytic oxidation reaction performances at low temperature. Finally, we hope this review will serve as a timely and useful research guide for rational design and utilization of the new type of monolithic catalysts.« less

Effect of Rational-Emotive Behavior Therapy Program on the Symptoms of Burnout Syndrome Among Undergraduate Electronics Work Students in Nigeria.

PubMed

Ogbuanya, Theresa C; Eseadi, Chiedu; Orji, Chibueze T; Omeje, Joachim C; Anyanwu, Joy I; Ugwoke, Samuel C; Edeh, Nkechinyere C

2018-01-01

This research aimed to investigate the effect that rational-emotive behavior therapy had on the symptoms of burnout among undergraduate electronics work students in Southeast Nigeria. This study utilized a pretest-posttest design involving a no-intervention group versus an intervention group. Participants were 124 undergraduate electronics work students who met the inclusion criteria of the study. The intervention consisted of 12 weeks of rational-emotive behavior therapy treatment and 2 weeks of follow-up meetings conducted at 6 months. Self-report questionnaire was used for data collection. Repeated measures analysis of variance and t test were used for data analysis. The results show that rational-emotive behavior therapy had a significant effect on the symptoms of burnout syndrome among the electronics work students in the treatment group compared to their counterparts in the no-intervention group. Finally, the positive gains were significantly maintained by the treatment group at the follow-up. The current study suggests that rational-emotive behavior therapy program can be effective for dealing with burnout syndrome among the population of undergraduates in Nigeria. Further clinical evaluation is needed.

Utilization of Cacao Pod Husk Silage as Cattle Ration Mixture at Taluditi, Pohuwatu Regency, Gorontalo Province

NASA Astrophysics Data System (ADS)

Hidayat, M.; Pratama, H. Y.; Martono, E.

2018-02-01

Cacao plantation produces cacao pod husks (CPHs) by-products during the harvest period. This research aimed to make benefits the CPH, preserved with silage technology as cattle ration mixture, investigate the adequacy of nutrient for the cattle after treated with addition of CPH silage, and investigate the quota of cattle treated with CPH silage addition. The research design was conducted by giving extension and field observation that was carried out at Taluditi on July to August 2015 during the activity of Student Community Service (KKN PPM UGM Unit Gorontalo 02). The secondary data was gathered from the Department of Agriculture and Plantation Pohuwatu Regency, and also supporting references. The number of respondents in each location was about 30 - 40 people. The research results showed that the silage preservation technology can be well received by the farmers. There was improvement of cattle ration nutrient supplemented with CPH compared to that of ration nutrient which was usually be used by the farmers or standard ration nutrient. The research also resulted in fresh CPH production 2,625.741 tons/year, CPH silage production 2,140.549 tons/year and load capacity + 575 heads/day weight 250-300 kg.

The limited impact of indeterminacy for healthcare rationing: how indeterminacy problems show the need for a hybrid theory, but nothing more.

PubMed

Herlitz, Anders

2016-01-01

A notorious debate in the ethics of healthcare rationing concerns whether to address rationing decisions with substantial principles or with a procedural approach. One major argument in favour of procedural approaches is that substantial principles are indeterminate so that we can reasonably disagree about how to apply them. To deal with indeterminacy, we need a just decision process. In this paper I argue that it is a mistake to abandon substantial principles just because they are indeterminate. It is true that reasonable substantial principles designed to deal with healthcare rationing can be expected to be indeterminate. Yet, the indeterminacy is only partial. In some situations we can fully determine what to do in light of the principles, in some situations we cannot. The conclusion to draw from this fact is not that we need to develop procedural approaches to healthcare rationing, but rather that we need a more complex theory in which both substantial principles and procedural approaches are needed. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Rational and Safe Design of Concrete Transportation Structures for Size Effect and Multi-Decade Sustainability

DOT National Transportation Integrated Search

2012-10-01

The overall goal of this project was to improve the safety and sustainability in the design of large : prestressed concrete bridges and other transportation structures. The safety of large concrete : structures, including bridges, has been insufficie...

DEVELOPMENT OF A RATIONALLY BASED DESIGN PROTOCOL FOR THE ULTRAVIOLET LIGHT DISINFECTION PROCESS

EPA Science Inventory

A protocol is demonstrated for the design and evaluation of ultraviolet (UV) disinfection systems based on a mathematical model. The disinfection model incorporates the system's physical dimensions, the residence time distribution of the reactor and dispersion characteristics, th...

SUSTAINABLE ALLOY DESIGN: SEARCHING FOR RARE EARTH ELEMENT ALTERNATIVES THROUGH CRYSTAL ENGINEERING

DTIC Science & Technology

2016-02-26

Property Maps to Guide Materials Design via Statistical Learning Summer Research Group Meeting – Materials by Design Los Alamos National Laboratory, July...Informatics, Rational design , Quantitative correlative spectroscopy and imaging, DFT, In situ high pressure mechanical property measurements, Superalloy...final, technical, interim, memorandum, master’s thesis, progress, quarterly, research , special, group study, etc. 3. DATES COVERED. Indicate the

Rational Design and Development of Lanthanide-Doped NaYF4@CdS-Au-RGO as Quaternary Plasmonic Photocatalysts for Harnessing Visible-Near-Infrared Broadband Spectrum.

PubMed

Kumar, Ajay; Reddy, Kumbam Lingeshwar; Kumar, Suneel; Kumar, Ashish; Sharma, Vipul; Krishnan, Venkata

2018-05-09

Utilization of the total solar spectrum efficiently for photocatalysis has remained a huge challenge for a long time. However, designing a system by rationally combining nanocomponents with complementary properties, such as upconversion nanoparticles, semiconductors, plasmonic metals, and carbonaceous support, offers a promising route for efficient utilization of solar energy by harnessing the broadband spectrum. In this work, a series of novel quaternary plasmonic photocatalysts comprising of lanthanide-doped NaYF 4 @CdS (UC) core-shell nanostructures decorated with Au nanoparticles (Au NPs) supported on reduced graphene oxide (RGO) nanosheets were prepared using the multistep hydrothermal method. The different components of the prepared nanocomposites could be efficiently employed to utilize both the visible and near-infrared (NIR) regions. Specifically in this work, the utility of these quaternary nanocomposites for photocatalytic degradation of a colorless pharmaceutical pollutant, ciprofloxacin, under visible and NIR light irradiations has been demonstrated. In comparison to bare counterparts, our quaternary nanocomposites exhibit an enhanced photocatalytic activity attributable to the synergistic effect of different components arranged in such a way that favors harnessing energy from the broad spectral region and efficient charge separation. The combination of upconversion and plasmonic properties along with the advantages of a carbonaceous support can provide new physical insights for further development of photocatalysts, which could utilize the broadband spectrum.