Recombination rate plasticity: revealing mechanisms by design

Science.gov (United States)

Sefick, Stephen; Rushton, Chase

2017-01-01

For over a century, scientists have known that meiotic recombination rates can vary considerably among individuals, and that environmental conditions can modify recombination rates relative to the background. A variety of external and intrinsic factors such as temperature, age, sex and starvation can elicit ‘plastic’ responses in recombination rate. The influence of recombination rate plasticity on genetic diversity of the next generation has interesting and important implications for how populations evolve. Further, many questions remain regarding the mechanisms and molecular processes that contribute to recombination rate plasticity. Here, we review 100 years of experimental work on recombination rate plasticity conducted in Drosophila melanogaster. We categorize this work into four major classes of experimental designs, which we describe via classic studies in D. melanogaster. Based on these studies, we highlight molecular mechanisms that are supported by experimental results and relate these findings to studies in other systems. We synthesize lessons learned from this model system into experimental guidelines for using recent advances in genotyping technologies, to study recombination rate plasticity in non-model organisms. Specifically, we recommend (1) using fine-scale genome-wide markers, (2) collecting time-course data, (3) including crossover distribution measurements, and (4) using mixed effects models to analyse results. To illustrate this approach, we present an application adhering to these guidelines from empirical work we conducted in Drosophila pseudoobscura. This article is part of the themed issue ‘Evolutionary causes and consequences of recombination rate variation in sexual organisms’. PMID:29109222

Design of 2-D rational digital filters

International Nuclear Information System (INIS)

Harris, D.B

1981-01-01

A novel 2-D rational filter design technique is presented which makes use of a reflection coefficient function (RCF) representation for the filter transfer function. The design problem is formulated in the frequency domain. A least-square error criterion is used though the usual error measure is augmented with barrier functions. These act to restrict the domain of approximation to the set of stable filters. Construction of suitable barrier functions is facilitated by the RCF characterization

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

Science.gov (United States)

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

Standby Gasoline Rationing Plan. Contingency gasoline rationing regulations

Energy Technology Data Exchange (ETDEWEB)

1979-02-01

The Economic Regulatory Administration issues final rules with respect to standby gasoline rationing. The plan is designed for and would be used only in the event of a severe gasoline shortage. The plan provides that eligibility for ration allotments will be primarily on the basis of motor vehicle registrations. DOE will mail government ration checks to the parties named in a national vehicle registration file to be maintained by DOE. Ration recipients may cash these checks for ration coupons at various designated coupon issuance points. Retail outlets and other suppliers will be required to redeem the ration coupons received in exchange for gasoline sold. Supplemental gas will be given to high-priority activities. A ration banking system will be established with two separate and distinct of ration accounts: retail outlets and other suppliers will open redemption accounts for the deposit of redeemed ration rights; and individuals or firms may open ration rights accounts, which will operate in much the same manner as monetary checking accounts. A white market will be permitted for the sale of transfer of ration rights. A percentage of the total ration rights to be issued will be reserved for distribution to the states as a State Ration Reserve, to be used by the states primarily for the relief of hardship. A National Ration Reserave will also be established. All sections of the Standby Gasoline Rationing Regulations are analyzed. (MCW)

RECENT ADVANCES TOWARDS THE RATIONAL DESIGN OF PEPTIDE DRUGS

OpenAIRE

YEŞİLADA, Akgül; ÖZKANLI, Fügen

2004-01-01

In this review, after a short introduction to definition and physiological roles of regulatory peptides, problems faced during the development of peptide drugs, studies directed to solve these problems and rational design of peptide drugs with special emphesis on peptidomimetics are mentioned

A rational approach for ω-transaminase-catalyzed process design

DEFF Research Database (Denmark)

T. Gundersen, Maria; Lloyd, Richard; Tufvesson, Pär

Herein we describe a novel rational approach to the design of a ω-transaminase process such that it will fulfill criteria necessary for industrial use. By first determining the fundamental properties of the reaction system, it is possible to suggest appropriate process strategies that may be used...

Design rationalization and the logic of design: a case study

DEFF Research Database (Denmark)

Galle, Per

1996-01-01

various ‘sources of credibility’ of premises, items of general background knowledge, and several (abductive and deductive) patterns of inference which suggest a possible ‘logic of design’. Rationalization of decisions is defined, and many decisions are found not to be fully rationalized, despite...... the apparent rationality of the reasoning....

Gas recombination device design and cost study. Final report

Energy Technology Data Exchange (ETDEWEB)

1980-07-01

Under a contract with Argonne National Laboratory, VARTA Batterie AG. conducted a design and cost study of hydrogen-oxygen recombination devices (HORD) for use with utility load-leveling lead-acid cells. Design specifications for the devices, through extensive calculation of the heat-flow conditions of the unit, were developed. Catalyst and condenser surface areas were specified. The exact dimensions can, however, be adjusted to the cell dimension and the space available above the cell. Design specifications were also developed for additional components required to ensure proper function of the recombination device, including metal hydride compound decomposer, aerosol retainer, and gas storage component. Costs for HORD were estimated to range from $4 to $10/kWh cell capacity for the production of a large number of units (greater than or equal to 10,000 units). The cost is a function of cell size and positive grid design. 21 figures, 2 tables.

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

Science.gov (United States)

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.

MIRATE: MIps RATional dEsign Science Gateway.

Science.gov (United States)

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.

Structure-based, rational design of T cell receptors

Directory of Open Access Journals (Sweden)

Vincent eZoete

2013-09-01

Full Text Available Adoptive cell transfer using engineered T cells is emerging as a promising treatment for metastatic melanoma. Such an approach allows one to introduce TCR modifications that, while maintaining the specificity for the targeted antigen, can enhance the binding and kinetic parameters for the interaction pMHC. Using the well-characterized 2C TCR/SIYR/H-2K(b structure as a model system, we demonstrated that a binding free energy decomposition based on the MM-GBSA approach provides a detailed and reliable description of the TCR/pMHC interactions at the structural and thermodynamic levels. Starting from this result, we developed a new structure-based approach, to rationally design new TCR sequences, and applied it to the BC1 TCR targeting the HLA-A2 restricted NY-ESO-1157-165 cancer-testis epitope. 54% of the designed sequence replacements exhibited improved pMHC-binding as compared to the native TCR, with up to 150 fold increase in affinity, while preserving specificity. Genetically-engineered CD8+ T cells expressing these modified TCRs showed an improved functional activity compared to those expressing BC1 TCR. We measured maximum levels of activities for TCRs within the upper limit of natural affinity. Beyond the affinity threshold at KD < 1 μM we observed an attenuation in cellular function. We have also developed a homology modeling-based approach, TCRep 3D, to obtain accurate structural models of any TCR-pMHC complexes. We have complemented the approach with a simplified rigid method to predict the TCR orientation over pMHC. These methods potentially extend the use of our TCR engineering method to entire TCR repertoires for which no X-ray structure is available. We have also performed a steered molecular dynamics study of the unbinding of the TCR-pMHC complex to get a better understanding of how TCRs interact with pMHCs. This entire rational TCR design pipeline is now being used to produce rationally optimized TCRs for adoptive cell therapies of

Site-Directed Mutagenesis of a Hyperthermophilic Endoglucanase Cel12B from Thermotoga maritima Based on Rational Design.

Directory of Open Access Journals (Sweden)

Jinfeng Zhang

Full Text Available To meet the demand for the application of high activity and thermostable cellulases in the production of new-generation bioethanol from nongrain-cellulose sources, a hyperthermostable β-1,4-endoglucase Cel12B from Thermotoga maritima was selected for further modification by gene site-directed mutagenesis method in the present study, based on homology modeling and rational design. As a result, two recombinant enzymes showed significant improvement in enzyme activity by 77% and 87%, respectively, higher than the parental enzyme TmCel12B. Furthermore, the two mutants could retain 80% and 90.5% of their initial activity after incubation at 80°C for 8 h, while only 45% for 5 h to TmCel12B. The Km and Vmax of the two recombinant enzymes were 1.97±0.05 mM, 4.23±0.15 μmol·mg(-1·min(-1 of TmCel12B-E225H-K207G-D37V, and 2.97±0.12 mM, 3.15±0.21 μmol·mg(-1·min(-1 of TmCel12B-E225H-K207G, respectively, when using CMC-Na as the substrate. The roles of the mutation sites were also analyzed and evaluated in terms of electron density, hydrophobicity of the modeled protein structures. The recombinant enzymes may be used in the hydrolysis of cellulose at higher temperature in the future. It was concluded that the gene mutagenesis approach of a certain active residues may effectively improve the performance of cellulases for the industrial applications and contribute to the study the thermostable mechanism of thermophilic enzymes.

Rationalization of design and construction of buildings for nuclear power plants

Energy Technology Data Exchange (ETDEWEB)

Satoh, Shunsaku; Mitsumatsu, Kazuo

1987-02-01

This article presents various rationalization methods introduced in the past few years for design and construction of BWR nuclear power plant buildings. When the site for a nuclear power plant has been decided, investigation is made on various aspects of possible earthquakes, based on which anti-earthquake design for the plant site is established. The next step is to examine the displacements and stresses that may occur to various parts of the bulding from a postulated earthquake. This is normally called the earthquake response analysis and consists of calculating the behaviors of the buildings using large computers. A seismic controlled structure system has recently proposed, aiming to reduce the displacements and stresses of the building itself by controlling the flexibility of the installed seismic apparatus against the input of external loads. Lately, high strength concrete and high strength reinforcing steel bars (rebars) are being considered for practical application. If advanced computers and related accessories are utilized to the maximum, it will lead not only to efficiency in the design work but to the possibility of optimized design. For rational construction, a combined scaffolding and temporary support has been devised to reduce the time and volume of required temporary work. What have been developed for rationalization of construction work also include robots for heavy weight rebar fabrication, horizontal reed blind type rebars, portable concrete distributor, all weather environment facilities, and construction materials conveyance system. (Nogami, K.).

Rationalization of design and construction of buildings for nuclear power plants

International Nuclear Information System (INIS)

Satoh, Shunsaku; Mitsumatsu, Kazuo

1987-01-01

This article presents various rationalization methods introduced in the past few years for design and construction of BWR nuclear power plant buildings. When the site for a nuclear power plant has been decided, investigation is made on various aspects of possible earthquakes, based on which anti-earthquake design for the plant site is established. The next step is to examine the displacements and stresses that may occur to various parts of the bulding from a postulated earthquake. This is normally called the earthquake response analysis and consists of calculating the behaviors of the buildings using large computers. A seismic controlled structure system has recently proposed, aiming to reduce the displacements and stresses of the building itself by controlling the flexibility of the installed seismic apparatus against the input of external loads. Lately, high strength concrete and high strength reinforcing steel bars (rebars) are being considered for practical application. If advanced computers and related accessories are utilized to the maximum, it will lead not only to efficiency in the design work but to the possibility of optimized design. For rational construction, a combined scaffolding and temporary support has been devised to reduce the time and volume of required temporary work. What have been developed for rationalization of construction work also include robots for heavy weight rebar fabrication, horizontal reed blind type rebars, portable concrete distributor, all weather environment facilities, and construction materials conveyance system. (Nogami, K.)

On rationally supported surfaces

DEFF Research Database (Denmark)

Gravesen, Jens; Juttler, B.; Sir, Z.

2008-01-01

We analyze the class of surfaces which are equipped with rational support functions. Any rational support function can be decomposed into a symmetric (even) and an antisymmetric (odd) part. We analyze certain geometric properties of surfaces with odd and even rational support functions....... In particular it is shown that odd rational support functions correspond to those rational surfaces which can be equipped with a linear field of normal vectors, which were discussed by Sampoli et al. (Sampoli, M.L., Peternell, M., Juttler, B., 2006. Rational surfaces with linear normals and their convolutions...... with rational surfaces. Comput. Aided Geom. Design 23, 179-192). As shown recently, this class of surfaces includes non-developable quadratic triangular Bezier surface patches (Lavicka, M., Bastl, B., 2007. Rational hypersurfaces with rational convolutions. Comput. Aided Geom. Design 24, 410426; Peternell, M...

Rational design of anatase TiO2 architecture with hierarchical nanotubes and hollow microspheres for high-performance dye-sensitized solar cells

Science.gov (United States)

Gu, Jiuwang; Khan, Javid; Chai, Zhisheng; Yuan, Yufei; Yu, Xiang; Liu, Pengyi; Wu, Mingmei; Mai, Wenjie

2016-01-01

Large surface area, sufficient light-harvesting and superior electron transport property are the major factors for an ideal photoanode of dye-sensitized solar cells (DSSCs), which requires rational design of the nanoarchitectures and smart integration of state-of-the-art technologies. In this work, a 3D anatase TiO2 architecture consisting of vertically aligned 1D hierarchical TiO2 nanotubes (NTs) with ultra-dense branches (HTNTs, bottom layer) and 0D hollow TiO2 microspheres with rough surface (HTS, top layer) is first successfully constructed on transparent conductive fluorine-doped tin oxide glass through a series of facile processes. When used as photoanodes, the DSSCs achieve a very large short-current density of 19.46 mA cm-2 and a high overall power conversion efficiency of 8.38%. The remarkable photovoltaic performance is predominantly ascribed to the enhanced charge transport capacity of the NTs (function as the electron highway), the large surface area of the branches (act as the electron branch lines), the pronounced light harvesting efficiency of the HTS (serve as the light scattering centers), and the engineered intimate interfaces between all of them (minimize the recombination effect). Our work demonstrates a possibility of fabricating superior photoanodes for high-performance DSSCs by rational design of nanoarchitectures and smart integration of multi-functional components.

Rational assembly of nanoparticle superlattices with designed lattice symmetries

Science.gov (United States)

Gang, Oleg; Lu, Fang; Tagawa, Miho

2017-09-05

A method for lattice design via multivalent linkers (LDML) is disclosed that introduces a rationally designed symmetry of connections between particles in order to achieve control over the morphology of their assembly. The method affords the inclusion of different programmable interactions within one linker that allow an assembly of different types of particles. The designed symmetry of connections is preferably provided utilizing DNA encoding. The linkers may include fabricated "patchy" particles, DNA scaffold constructs and Y-shaped DNA linkers, anisotropic particles, which are preferably functionalized with DNA, multimeric protein-DNA complexes, and particles with finite numbers of DNA linkers.

Rational design of an EGF-IL18 fusion protein: Implication for developing tumor therapeutics

International Nuclear Information System (INIS)

Lu Jianxin; Peng Ying; Meng Zhefeng; Jin Liqin; Lu Yongsui; Guan Minxin

2005-01-01

Interleukin-18 (IL-18) is a proinflammatory cytokine. This protein has a role in regulating immune responses and exhibits significant anti-tumor activities. Epidermal growth factor (EGF) is an important growth factor that plays a central role in the regulation of cell cycle and differentiation. It was proposed that a targeted delivery of IL-18 by generation of IL-18-EGF fusion protein might decrease adverse effects and result in enhancing cytotoxic and antitumor activities. In the present study, a fusion protein, consisting of EGFR binding domain fused to human IL-18 mature peptide via a linker peptide of (Gly 4 Ser) 3, was constructed and expressed in the insect cell line Sf9 using Bac-to-Bac baculovirus expression system. We showed that the purified recombinant fusion protein induced similar levels of IFN-γ to that of native IL-18 protein in human PBMC in the presence of ConA. Furthermore, EGF receptor competitive test in human epithelial cancer A431 cell line showed that EGF-IL18 fusion protein can specifically bind with EGFR by competing with native EGF protein. These suggest that this rationally designed protein can be further developed as novel tumor therapeutics

Rational design of soft mechanical metamaterials : Independent tailoring of elastic properties with randomness

NARCIS (Netherlands)

Mirzaali Mazandarani, M.J.; Hedayati, R.; Vena, P; Vergani, L.; Strano, M.; Zadpoor, A.A.

2017-01-01

The elastic properties of mechanical metamaterials are direct functions of their topological designs. Rational design approaches based on computational models could, therefore, be used to devise topological designs that result in the desired properties. It is of particular importance to

Harvesting bioenergy with rationally designed complex functional materials

Science.gov (United States)

Kuang, Liangju

A key challenge in renewable energy is to capture, convert and store solar power with earth-abundant materials and environmentally benign technologies. The goal of this thesis is to develop rationally designed complex functional materials for bio-renewable energy applications. On one hand, photoconversion membrane proteins (MPs) are nature's nanoengineering feats for renewable energy management. Harnessing their functions in synthetic systems could help understand, predict, and ultimately control matter and energy at the nanoscale. This is particularly enticing in the post-genome era as recombinant or cell-free expression of many MPs with high yields becomes possible. However, the labile nature of lipid bilayers renders them unsuitable for use in a broad range of engineered systems. A knowledge gap exists about how to design robust synthetic nanomembranes as lipid-bilayer-mimics to support MP functions and how to direct hierarchical MP reconstitution into those membranes to form 2-D or 3-D ordered proteomembrane arrays. Our studies on proteorhodopsin (PR) and bacterial reaction center (BRC), the two light-harvesting MPs, reveal that a charge-interaction-directed reconstitution (CIDR) mechanism induces spontaneous reconstitution of detergent-solubilized MPs into various amphiphilic block copolymer membranes, many of which have far superior stability than lipid bilayers. Our preliminary data also suggest MPs are not enslaved by the biological membranes they derive from; rather, the chemically nonspecific material properties of MP-supporting membranes may act as allosteric regulators. Versatile chemical designs are possible to modulate the conformational energetics of MPs, hence their transport performance in synthetic systems. On the other hand, microalgae are widely regarded as a sustainable feedstock for biofuel production. Microalgae-derived biofuels have not been commercialized yet because current technologies for microalgae dewatering add a huge cost to the

Does decision documentation help junior designers rationalize their decisions? A comparative multiple-case study

NARCIS (Netherlands)

Heesch, U. van; Avgeriou, P.; Tang, A.

Software architecture design is challenging, especially for junior software designers. Lacking practice and experience, junior designers need process support in order to make rational architecture decisions. In this paper, we present the results of a comparative multiple-case study conducted to find

Fundamental understanding and rational design of high energy structural microbatteries

Energy Technology Data Exchange (ETDEWEB)

Wang, Yuxing; Li, Qiuyan; Cartmell, Samuel; Li, Huidong; Mendoza, Sarah; Zhang, Ji-Guang; Deng, Zhiqun Daniel; Xiao, Jie

2018-01-01

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 in designing the structural microbatteries for emerging technologies.

Reiterative Recombination for the in vivo assembly of libraries of multigene pathways.

Science.gov (United States)

Wingler, Laura M; Cornish, Virginia W

2011-09-13

The increasing sophistication of synthetic biology is creating a demand for robust, broadly accessible methodology for constructing multigene pathways inside of the cell. Due to the difficulty of rationally designing pathways that function as desired in vivo, there is a further need to assemble libraries of pathways in parallel, in order to facilitate the combinatorial optimization of performance. While some in vitro DNA assembly methods can theoretically make libraries of pathways, these techniques are resource intensive and inherently require additional techniques to move the DNA back into cells. All previously reported in vivo assembly techniques have been low yielding, generating only tens to hundreds of constructs at a time. Here, we develop "Reiterative Recombination," a robust method for building multigene pathways directly in the yeast chromosome. Due to its use of endonuclease-induced homologous recombination in conjunction with recyclable markers, Reiterative Recombination provides a highly efficient, technically simple strategy for sequentially assembling an indefinite number of DNA constructs at a defined locus. In this work, we describe the design and construction of the first Reiterative Recombination system in Saccharomyces cerevisiae, and we show that it can be used to assemble multigene constructs. We further demonstrate that Reiterative Recombination can construct large mock libraries of at least 10(4) biosynthetic pathways. We anticipate that our system's simplicity and high efficiency will make it a broadly accessible technology for pathway construction and render it a valuable tool for optimizing pathways in vivo.

Advanced design and modeling concepts for recombination x-ray lasers

International Nuclear Information System (INIS)

Eder, D.C.; Rosen, M.D.; Shephard, R.; Staffin, R.; Nash, J.K.; Keane, C.J.

1990-01-01

Geometric, kinetic, and trapping issues, in short and ultrashort recombination x-ray lasers, are discussed. The design of a composite target consisting of a lasant strip on a plastic backing is described. Examples of modeling showing the effect of photon trapping and uncertainties in other physical processes on calculated gain coefficients are given. A simple and accurate expression for photon trapping in cylindrical geometry is presented. Recombination lasers that have the ground state as the lower laser state are shown to have small I sat 's and corresponding low efficiencies. Scaling laws for femtosecond laser-plasma interactions are presented. 19 refs

Rational Multiparty Computation

OpenAIRE

Wallrabenstein, John Ross

2014-01-01

The field of rational cryptography considers the design of cryptographic protocols in the presence of rational agents seeking to maximize local utility functions. This departs from the standard secure multiparty computation setting, where players are assumed to be either honest or malicious. ^ We detail the construction of both a two-party and a multiparty game theoretic framework for constructing rational cryptographic protocols. Our framework specifies the utility function assumptions neces...

Designing institutions for climate change: Why rational design involves technology

Energy Technology Data Exchange (ETDEWEB)

Coninck, H. de [Energy Research Centre of the Netherlands, Petten (Netherlands)

2008-09-30

This paper aims to explore how to augment the institutional solutions offered by current political theory for addressing the unprecedented problem of climate change. Although steering directly at emission reductions in an international treaty has benefits in terms of cost-effectiveness, the paper arrives at the conclusion that considerations around technological development should be drawn into the treaty equation in order to generate sufficient reciprocity to have a politically feasible international regime. It then argues that the benefits of technology agreements for climate change mitigation may be larger than commonly assumed, as they - if properly designed - could lead to real emission reductions and provide more flexibility to reach agreement in post-2012 negotiations than proposals modelled exclusively on the Kyoto Protocol or other types of absolute emission targets. Based on rational design of international institutions for environmental governance, and attempting to take into account considerations of technological dynamics and the 'sociotechnical system', contours of a possible environmentally effective and politically feasible international climate change agreements are sketched.

Fundamental understanding and rational design of high energy structural microbatteries

International Nuclear Information System (INIS)

Wang, Yuxing; Li, Qiuyan; Cartmell, Samuel; Li, Huidong; Mendoza, Sarah

2017-01-01

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 during the rolling process are discussed providing new insights in designing the structural microbatteries for emerging technologies.

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

Directory of Open Access Journals (Sweden)

Charles H. Williams

2011-04-01

Full Text Available 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.

Rational Design of Semiconductor Nanostructures for Functional Subcellular Interfaces.

Science.gov (United States)

Parameswaran, Ramya; Tian, Bozhi

2018-05-15

One of the fundamental questions guiding research in the biological sciences is how cellular systems process complex physical and environmental cues and communicate with each other across multiple length scales. Importantly, aberrant signal processing in these systems can lead to diseases that can have devastating impacts on human lives. Biophysical studies in the past several decades have demonstrated that cells can respond to not only biochemical cues but also mechanical and electrical ones. Thus, the development of new materials that can both sense and modulate all of these pathways is necessary. Semiconducting nanostructures are an emerging class of discovery platforms and tools that can push the limits of our ability to modulate and sense biological behaviors for both fundamental research and clinical applications. These materials are of particular interest for interfacing with cellular systems due to their matched dimension with subcellular components (e.g., cytoskeletal filaments), and easily tunable properties in the electrical, optical and mechanical regimes. Rational design via traditional or new approaches, such as nanocasting and mesoscale chemical lithography, can allow us to control micro- and nanoscale features in nanowires to achieve new biointerfaces. Both processes endogenous to the target cell and properties of the material surface dictate the character of these interfaces. In this Account, we focus on (1) approaches for the rational design of semiconducting nanowires that exhibit unique structures for biointerfaces, (2) recent fundamental discoveries that yield robust biointerfaces at the subcellular level, (3) intracellular electrical and mechanical sensing, and (4) modulation of cellular behaviors through material topography and remote physical stimuli. In the first section, we discuss new approaches for the synthetic control of micro- and nanoscale features of these materials. In the second section, we focus on achieving biointerfaces with

Rational design and application of responsive α-helical peptide hydrogels

Science.gov (United States)

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

Geology and Design: Formal and Rational Connections

Science.gov (United States)

Eriksson, S. C.; Brewer, J.

2016-12-01

Geological forms and the manmade environment have always been inextricably linked. From the time that Upper Paleolithic man created drawings in the Lascaux Caves in the southwest of France, geology has provided a critical and dramatic spoil for human creativity. This inspiration has manifested itself in many different ways, and the history of architecture is rife with examples of geologically derived buildings. During the early 20th Century, German Expressionist art and architecture was heavily influenced by the natural and often translucent quality of minerals. Architects like Bruno Taut drew and built crystalline forms that would go on to inspire the more restrained Bauhaus movement. Even within the context of Contemporary architecture, geology has been a fertile source for inspiration. Architectural practices across the globe leverage the rationality and grounding found in geology to inform a process that is otherwise dominated by computer-driven parametric design. The connection between advanced design technology and the beautifully realized geo natural forms insures that geology will be a relevant source of architectural inspiration well into the 21st century. The sometimes hidden relationship of geology to the various sub-disciplines of Design such as Architecture, Interiors, Landscape Architecture, and Historic Preservation is explored in relation to curriculum and the practice of design. Topics such as materials, form, history, the cultural and physical landscape, natural hazards, and global design enrich and inform curriculum across the college. Commonly, these help define place-based education.

Structured morphological modeling as a framework for rational strain design of Streptomyces species

NARCIS (Netherlands)

Celler, K.; Picioreanu, C.; Van Loosdrecht, M.C.M.; Van Wezel, G.P.

2012-01-01

Successful application of a computational model for rational design of industrial Streptomyces exploitation requires a better understanding of the relationship between morphology—dictated by microbial growth, branching, fragmentation and adhesion—and product formation. Here we review the

Nucleic acids for the rational design of reaction circuits.

Science.gov (United States)

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.

Rational use of water in trickle irrigation design.

Science.gov (United States)

Saad, J. C. C.; da Silva Junior, H. M.

2012-04-01

In trickle irrigation systems, the design is based on the pre-established emission uniformity (EU) which is the combined result of the equipment characteristics and its hydraulic configuration. However, this desired value of the EU may not be confirmed by the final project (in field conditions) and neither by the yield uniformity. However, the most important is to assure yield uniformity with rational use of water. The hypotheses of this research were: a) the EU of a trickle irrigation system at field conditions is equal to the emission uniformity pre-established in the design; b) EU has always the lowest value when compared with other indicators of uniformity; c) the discharge variation coefficient is not equal to production variation coefficient in the operational unit; d) the productivity variation coefficient is more dependent on water depth applied than the EU. This study aimed to evaluate the relationships among EU used in the irrigation system design, water depth applied and the final yield uniformity. The uniformity indicators evaluated were: EU, distribution uniformity (UD) and the index proposed by Barragan & Wu (2005). They were compared estimating the performance of a trickle irrigation system applied in a citrus orchard with dimensions of 400m x 600m. The design of the irrigation system was optimized by a Linear Programming model. The tree rows were leveled in the larger direction and the spacing adopted in the orchard was 7m x 4m. The manifold line was always operating on a slope condition. The sensitivity analysis involved different slopes, 0, 3, 6, 9 and 12%, and different values of emission uniformity, 60, 70, 75, 80, 85, 90 and 94%. The citrus yield uniformity was evaluated by the variation coefficient. The emission uniformity (EU) after design differed from the EU pre-established, more sharply in the initial values lower than 90%. Comparing the uniformity indexes, the EU always generated lower values when compared with the UD and with the index

Rational drug design paradigms: the odyssey for designing better drugs.

Science.gov (United States)

Kellici, Tahsin; Ntountaniotis, Dimitrios; Vrontaki, Eleni; Liapakis, George; Moutevelis-Minakakis, Panagiota; Kokotos, George; Hadjikakou, Sotiris; Tzakos, Andreas G; Afantitis, Antreas; Melagraki, Georgia; Bryant, Sharon; Langer, Thierry; Di Marzo, Vincenzo; Mavromoustakos, Thomas

2015-01-01

Due to the time and effort requirements for the development of a new drug, and the high attrition rates associated with this developmental process, there is an intense effort by academic and industrial researchers to find novel ways for more effective drug development schemes. The first step in the discovery process of a new drug is the identification of the lead compound. The modern research tendency is to avoid the synthesis of new molecules based on chemical intuition, which is time and cost consuming, and instead to apply in silico rational drug design. This approach reduces the consumables and human personnel involved in the initial steps of the drug design. In this review real examples from our research activity aiming to discover new leads will be given for various dire warnings diseases. There is no recipe to follow for discovering new leads. The strategy to be followed depends on the knowledge of the studied system and the experience of the researchers. The described examples constitute successful and unsuccessful efforts and reflect the reality which medicinal chemists have to face in drug design and development. The drug stability is also discussed in both organic molecules and metallotherapeutics. This is an important issue in drug discovery as drug metabolism in the body can lead to various toxic and undesired molecules.

Conditional genomic rearrangement by designed meiotic recombination using VDE (PI-SceI) in yeast.

Science.gov (United States)

Fukuda, Tomoyuki; Ohya, Yoshikazu; Ohta, Kunihiro

2007-10-01

Meiotic recombination plays critical roles in the acquisition of genetic diversity and has been utilized for conventional breeding of livestock and crops. The frequency of meiotic recombination is normally low, and is extremely low in regions called "recombination cold domains". Here, we describe a new and highly efficient method to modulate yeast meiotic gene rearrangements using VDE (PI-SceI), an intein-encoded endonuclease that causes an efficient unidirectional meiotic gene conversion at its recognition sequence (VRS). We designed universal targeting vectors, by use of which the strain that inserts the VRS at a desired site is acquired. Meiotic induction of the strains provided unidirectional gene conversions and frequent genetic rearrangements of flanking genes with little impact on cell viability. This system thus opens the way for the designed modulation of meiotic gene rearrangements, regardless of recombinational activity of chromosomal domains. Finally, the VDE-VRS system enabled us to conduct meiosis-specific conditional knockout of genes where VDE-initiated gene conversion disrupts the target gene during meiosis, serving as a novel approach to examine the functions of genes during germination of resultant spores.

Technique on rationalization of using electricity and cases

International Nuclear Information System (INIS)

1988-04-01

This book deals with rationalization of using electric and cases. It is divided into four parts. The first part introduces necessity and of progression rationalization of using electric. The second part describes the technique on rationalization of using electric with management of electric energy. The third part depicts domestic cases of rationalization on using of electric such as substation and motor. The last part also introduces foreign cases of rationalization on using of electric with measure of generator circuit, design of motor, design of lighting and design of other equipment.

Rational design of human metapneumovirus live attenuated vaccine candidates by inhibiting viral mRNA cap methyltransferase.

Science.gov (United States)

Zhang, Yu; Wei, Yongwei; Zhang, Xiaodong; Cai, Hui; Niewiesk, Stefan; Li, Jianrong

2014-10-01

The paramyxoviruses human respiratory syncytial virus (hRSV), human metapneumovirus (hMPV), and human parainfluenza virus type 3 (hPIV3) are responsible for the majority of pediatric respiratory diseases and inflict significant economic loss, health care costs, and emotional burdens. Despite major efforts, there are no vaccines available for these viruses. The conserved region VI (CR VI) of the large (L) polymerase proteins of paramyxoviruses catalyzes methyltransferase (MTase) activities that typically methylate viral mRNAs at positions guanine N-7 (G-N-7) and ribose 2'-O. In this study, we generated a panel of recombinant hMPVs carrying mutations in the S-adenosylmethionine (SAM) binding site in CR VI of L protein. These recombinant viruses were specifically defective in ribose 2'-O methylation but not G-N-7 methylation and were genetically stable and highly attenuated in cell culture and viral replication in the upper and lower respiratory tracts of cotton rats. Importantly, vaccination of cotton rats with these recombinant hMPVs (rhMPVs) with defective MTases triggered a high level of neutralizing antibody, and the rats were completely protected from challenge with wild-type rhMPV. Collectively, our results indicate that (i) amino acid residues in the SAM binding site in the hMPV L protein are essential for 2'-O methylation and (ii) inhibition of mRNA cap MTase can serve as a novel target to rationally design live attenuated vaccines for hMPV and perhaps other paramyxoviruses, such as hRSV and hPIV3. Human paramyxoviruses, including hRSV, hMPV, and hPIV3, cause the majority of acute upper and lower respiratory tract infections in humans, particularly in infants, children, the elderly, and immunocompromised individuals. Currently, there is no licensed vaccine available. A formalin-inactivated vaccine is not suitable for these viruses because it causes enhanced lung damage upon reinfection with the same virus. A live attenuated vaccine is the most promising

Rational Design of Bacillus coagulans NL01 l-Arabinose Isomerase and Use of Its F279I Variant in d-Tagatose Production.

Science.gov (United States)

Zheng, Zhaojuan; Mei, Wending; Xia, Meijuan; He, Qin; Ouyang, Jia

2017-06-14

d-Tagatose is a prospective functional sweetener that can be produced by l-arabinose isomerase (AI) from d-galactose. To improve the activity of AI toward d-galactose, the AI of Bacillus coagulans was rationally designed on the basis of molecular modeling and docking. After alanine scanning and site-saturation mutagenesis, variant F279I that exhibited improved activity toward d-galactose was obtained. The optimal temperature and pH of F279I were determined to be 50 °C and 8.0, respectively. This variant possessed 1.4-fold catalytic efficiency compared with the wild-type (WT) enzyme. The recombinant Escherichia coli overexpressing F279I also showed obvious advantages over the WT in biotransformation. Under optimal conditions, 67.5 and 88.4 g L -1 d-tagatose could be produced from 150 and 250 g L -1 d-galactose, respectively, in 15 h. The biocatalyst constructed in this study presents a promising alternative for large-scale d-tagatose production.

Rational design of the exchange-spring permanent magnet.

Science.gov (United States)

Jiang, J S; Bader, S D

2014-02-12

The development of the optimal exchange-spring permanent magnet balances exchange hardening, magnetization enhancement, and the feasibility of scalable fabrication. These requirements can be met with a rational design of the microstructural characteristics. The magnetization processes in several model exchange-spring structures with different geometries have been analyzed with both micromagnetic simulations and nucleation theory. The multilayer geometry and the soft-cylinders-in-hard-matrix geometry have the highest achievable figure of merit (BH)max, while the soft-spheres-in-hard-matrix geometry has the lowest upper limit for (BH)max. The cylindrical geometry permits the soft phase to be larger and does not require strict size control. Exchange-spring permanent magnets based on the cylindrical geometry may be amenable to scaled-up fabrication.

Rational design of the exchange-spring permanent magnet

International Nuclear Information System (INIS)

Jiang, J S; Bader, S D

2014-01-01

The development of the optimal exchange-spring permanent magnet balances exchange hardening, magnetization enhancement, and the feasibility of scalable fabrication. These requirements can be met with a rational design of the microstructural characteristics. The magnetization processes in several model exchange-spring structures with different geometries have been analyzed with both micromagnetic simulations and nucleation theory. The multilayer geometry and the soft-cylinders-in-hard-matrix geometry have the highest achievable figure of merit (BH) max , while the soft-spheres-in-hard-matrix geometry has the lowest upper limit for (BH) max . The cylindrical geometry permits the soft phase to be larger and does not require strict size control. Exchange-spring permanent magnets based on the cylindrical geometry may be amenable to scaled-up fabrication. (paper)

Does decision documentation help junior designers rationalize their decisions? A comparative multiple-case study

OpenAIRE

Heesch, U. van; Avgeriou, P.; Tang, A.

2013-01-01

Software architecture design is challenging, especially for junior software designers. Lacking practice and experience, junior designers need process support in order to make rational architecture decisions. In this paper, we present the results of a comparative multiple-case study conducted to find out if decision viewpoints from van Heesch et al. (2012, in press) can provide such a support. The case study was conducted with four teams of software engineering students working in industrial s...

Principles underlying rational design of live attenuated influenza vaccines

Science.gov (United States)

Jang, Yo Han

2012-01-01

Despite recent innovative advances in molecular virology and the developments of vaccines, influenza virus remains a serious burden for human health. Vaccination has been considered a primary countermeasure for prevention of influenza infection. Live attenuated influenza vaccines (LAIVs) are particularly attracting attention as an effective strategy due to several advantages over inactivated vaccines. Cold-adaptation, as a classical means for attenuating viral virulence, has been successfully used for generating safe and effective donor strains of LAIVs against seasonal epidemics and occasional pandemics. Recently, the advent of reverse genetics technique expedited a variety of rational strategies to broaden the pool of LAIVs. Considering the breadth of antigenic diversity of influenza virus, the pool of LAIVs is likely to equip us with better options for controlling influenza pandemics. With a brief reflection on classical attenuating strategies used at the initial stage of development of LAIVs, especially on the principles underlying the development of cold-adapted LAIVs, we further discuss and outline other attenuation strategies especially with respect to the rationales for attenuation, and their practicality for mass production. Finally, we propose important considerations for a rational vaccine design, which will provide us with practical guidelines for improving the safety and effectiveness of LAIVs. PMID:23596576

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

Science.gov (United States)

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

2015-01-01

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

Standby Gasoline Rationing Plan

Energy Technology Data Exchange (ETDEWEB)

None

1980-06-01

The final rules adopted by the President for a Standby Gasoline Rationing Plan are presented. The plan provides that eligibility for ration allotments will be determined primarily on the basis of motor vehicle registrations, taking into account historical differences in the use of gasoline among states. The regulations also provide authority for supplemental allotments to firms so that their allotment will equal a specified percentage of gasoline use during a base period. Priority classifications, i.e., agriculture, defense, etc., are established to assure adequate gasoline supplies for designated essential services. Ration rights must be provided by end-users to their suppliers for each gallon sold. DOE will regulate the distribution of gasoline at the wholesale level according to the transfer by suppliers of redeemed ration rights and the gasoline allocation regulations. Ration rights are transferable. A ration banking system is created to facilitate transfers of ration rights. Each state will be provided with a reserve of ration rights to provide for hardship needs and to alleviate inequities. (DC)

Rationally designed synthetic protein hydrogels with predictable mechanical properties.

Science.gov (United States)

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

2018-02-12

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

  A rationally designed tyrosine hydroxylase DNA vaccine induces specific antineuroblastoma immunity

DEFF Research Database (Denmark)

Huebener, Nicole; Fest, Stefan; Strandsby, Anne Bystrup

2008-01-01

Therapeutic vaccination against tumor antigens without induction of autoimmunity remains a major challenge in cancer immunotherapy. Here, we show for the first time effective therapeutic vaccination followed by suppression of established spontaneous neuroblastoma metastases using a tyrosine...... show effective therapeutic vaccination against neuroblastoma with a novel rationally designed TH minigene vaccine without induction of autoimmunity providing an important baseline for future clinical application of this strategy....

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

Science.gov (United States)

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.

Science.gov (United States)

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.

Theoretical rationalization for reduced charge recombination in bulky carbazole-based sensitizers in solar cells.

Science.gov (United States)

Surakhot, Yaowarat; Laszlo, Viktor; Chitpakdee, Chirawat; Promarak, Vinich; Sudyoadsuk, Taweesak; Kungwan, Nawee; Kowalczyk, Tim; Irle, Stephan; Jungsuttiwong, Siriporn

2017-05-05

The search for greater efficiency in organic dye-sensitized solar cells (DSCs) and in their perovskite cousins is greatly aided by a more complete understanding of the spectral and morphological properties of the photoactive layer. This investigation resolves a discrepancy in the observed photoconversion efficiency (PCE) of two closely related DSCs based on carbazole-containing D-π-A organic sensitizers. Detailed theoretical characterization of the absorption spectra, dye adsorption on TiO 2 , and electronic couplings for charge separation and recombination permit a systematic determination of the origin of the difference in PCE. Although the two dyes produce similar spectral features, ground- and excited-state density functional theory (DFT) simulations reveal that the dye with the bulkier donor group adsorbs more strongly to TiO 2 , experiences limited π-π aggregation, and is more resistant to loss of excitation energy via charge recombination on the dye. The effects of conformational flexibility on absorption spectra and on the electronic coupling between the bright exciton and charge-transfer states are revealed to be substantial and are characterized through density-functional tight-binding (DFTB) molecular dynamics sampling. These simulations offer a mechanistic explanation for the superior open-circuit voltage and short-circuit current of the bulky-donor dye sensitizer and provide theoretical justification of an important design feature for the pursuit of greater photocurrent efficiency in DSCs. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Design for Additive Bio-Manufacturing: From Patient-Specific Medical Devices to Rationally Designed Meta-Biomaterials.

Science.gov (United States)

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

Directory of Open Access Journals (Sweden)

Amir A. Zadpoor

2017-07-01

Full Text Available 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.

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

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

Marc H. V. Van Regenmortel

2018-01-01

Full Text Available 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 modular design of metabolic network for efficient production of plant polyphenol pinosylvin.

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Rational Emotive Education

Science.gov (United States)

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)

A Rapid and Improved Method to Generate Recombinant Dengue Virus Vaccine Candidates.

Science.gov (United States)

Govindarajan, Dhanasekaran; Guan, Liming; Meschino, Steven; Fridman, Arthur; Bagchi, Ansu; Pak, Irene; ter Meulen, Jan; Casimiro, Danilo R; Bett, Andrew J

2016-01-01

Dengue is one of the most important mosquito-borne infections accounting for severe morbidity and mortality worldwide. Recently, the tetravalent chimeric live attenuated Dengue vaccine Dengvaxia® was approved for use in several dengue endemic countries. In general, live attenuated vaccines (LAV) are very efficacious and offer long-lasting immunity against virus-induced disease. Rationally designed LAVs can be generated through reverse genetics technology, a method of generating infectious recombinant viruses from full length cDNA contained in bacterial plasmids. In vitro transcribed (IVT) viral RNA from these infectious clones is transfected into susceptible cells to generate recombinant virus. However, the generation of full-length dengue virus cDNA clones can be difficult due to the genetic instability of viral sequences in bacterial plasmids. To circumvent the need for a single plasmid containing a full length cDNA, in vitro ligation of two or three cDNA fragments contained in separate plasmids can be used to generate a full-length dengue viral cDNA template. However, in vitro ligation of multiple fragments often yields low quality template for IVT reactions, resulting in inconsistent low yield RNA. These technical difficulties make recombinant virus recovery less efficient. In this study, we describe a simple, rapid and efficient method of using LONG-PCR to recover recombinant chimeric Yellow fever dengue (CYD) viruses as potential dengue vaccine candidates. Using this method, we were able to efficiently generate several viable recombinant viruses without introducing any artificial mutations into the viral genomes. We believe that the techniques reported here will enable rapid and efficient recovery of recombinant flaviviruses for evaluation as vaccine candidates and, be applicable to the recovery of other RNA viruses.

Potency assay design for adjuvanted recombinant proteins as malaria vaccines.

Science.gov (United States)

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

2006-05-15

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

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

Science.gov (United States)

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.

Attenuation of Vibrio fischeri quorum sensing using rationally designed polymers.

Science.gov (United States)

Piletska, Elena V; Stavroulakis, Georgios; Karim, Kal; Whitcombe, Michael J; Chianella, Iva; Sharma, Anant; Eboigbodin, Kevin E; Robinson, Gary K; Piletsky, Sergey A

2010-04-12

A first attempt to attenuate the quorum sensing (QS) of a marine heterotroph microorganism, Vibrio fischeri , using signal molecule-sequestering polymers (SSPs) is presented. A set of rationally designed polymers with affinity toward a signal molecule of V. fischeri , N-(beta-ketocaproyl)-l-homoserine lactone (3-oxo-C6-AHL) was produced. It is reported that computationally designed polymers could sequester a signal molecule of V. fischeri and prevent QS-controlled phenotypes (in this case, bioluminescence) from being up-regulated. It was proven that the attenuation of bioluminescence of V. fischeri was due to sequestration of the signal molecule by specific polymers and not due to the toxicity of polymer or nonspecific depletion of nutrients. The ability to disrupt the bacterial communication using easy to synthesize and chemically inert polymers could provide a new concept for the development of pharmaceuticals and susceptible device coatings such as catheters.

Considerations for the rational design of a Chlamydia vaccine.

Science.gov (United States)

Liang, Steven; Bulir, David; Kaushic, Charu; Mahony, James

2017-04-03

Chlamydia trachomatis is the leading cause of preventable blindness and the most common bacterial sexually transmitted infection. Remarkable progress in vaccine research over the past six decades has led to the advancement of novel C. trachomatis vaccine candidates into clinical trials. However, many questions regarding the role of specific cellular populations and molecular mechanisms in protective immunity against human C. trachomatis genital tract infections remain unanswered. Biomarkers of vaccine induced protective immunity are elusive in humans, while a cautionary message on the translatability of data obtained from current animal models has emanated from vaccine research and development efforts against other important human pathogens. In this commentary, we highlight recent advances in Chlamydia vaccine development and discuss their implications in the context of a rational approach to the design of a human C. trachomatis vaccine.

Development of rational design technique for frame steel structure combining seismic resistance and economic performance

International Nuclear Information System (INIS)

Kato, Motoki; Morishita, Kunihiro; Shimono, Masaki; Chuman, Yasuharu; Okafuji, Takashi; Monaka, Toshiaki

2015-01-01

Anti-seismic designs have been applied to plant support steel frames for years. Today, a rational structure that further improves seismic resistance and ensures economic performance is required in response to an increase of seismic load on the assumption of predicted future massive earthquakes. For satisfying this requirement, a steel frame design method that combines a steel frame weight minimizing method, which enables economic design through simultaneous minimization of multiple steel frame materials, and a seismic response control design technology that improves seismic resistance has been established. Its application in the design of real structures has been promoted. This paper gives an overview of this design technology and presents design examples to which this design technology is applied. (author)

A Rapid and Improved Method to Generate Recombinant Dengue Virus Vaccine Candidates.

Directory of Open Access Journals (Sweden)

Dhanasekaran Govindarajan

Full Text Available Dengue is one of the most important mosquito-borne infections accounting for severe morbidity and mortality worldwide. Recently, the tetravalent chimeric live attenuated Dengue vaccine Dengvaxia® was approved for use in several dengue endemic countries. In general, live attenuated vaccines (LAV are very efficacious and offer long-lasting immunity against virus-induced disease. Rationally designed LAVs can be generated through reverse genetics technology, a method of generating infectious recombinant viruses from full length cDNA contained in bacterial plasmids. In vitro transcribed (IVT viral RNA from these infectious clones is transfected into susceptible cells to generate recombinant virus. However, the generation of full-length dengue virus cDNA clones can be difficult due to the genetic instability of viral sequences in bacterial plasmids. To circumvent the need for a single plasmid containing a full length cDNA, in vitro ligation of two or three cDNA fragments contained in separate plasmids can be used to generate a full-length dengue viral cDNA template. However, in vitro ligation of multiple fragments often yields low quality template for IVT reactions, resulting in inconsistent low yield RNA. These technical difficulties make recombinant virus recovery less efficient. In this study, we describe a simple, rapid and efficient method of using LONG-PCR to recover recombinant chimeric Yellow fever dengue (CYD viruses as potential dengue vaccine candidates. Using this method, we were able to efficiently generate several viable recombinant viruses without introducing any artificial mutations into the viral genomes. We believe that the techniques reported here will enable rapid and efficient recovery of recombinant flaviviruses for evaluation as vaccine candidates and, be applicable to the recovery of other RNA viruses.

Application of Absorption Modeling in Rational Design of Drug Product Under Quality-by-Design Paradigm.

Science.gov (United States)

Kesisoglou, Filippos; Mitra, Amitava

2015-09-01

Physiologically based absorption models can be an important tool in understanding product performance and hence implementation of Quality by Design (QbD) in drug product development. In this report, we show several case studies to demonstrate the potential application of absorption modeling in rational design of drug product under the QbD paradigm. The examples include application of absorption modeling—(1) prior to first-in-human studies to guide development of a formulation with minimal sensitivity to higher gastric pH and hence reduced interaction when co-administered with PPIs and/or H2RAs, (2) design of a controlled release formulation with optimal release rate to meet trough plasma concentrations and enable QD dosing, (3) understanding the impact of API particle size distribution on tablet bioavailability and guide formulation design in late-stage development, (4) assess impact of API phase change on product performance to guide specification setting, and (5) investigate the effect of dissolution rate changes on formulation bioperformance and enable appropriate specification setting. These case studies are meant to highlight the utility of physiologically based absorption modeling in gaining a thorough understanding of the product performance and the critical factors impacting performance to drive design of a robust drug product that would deliver the optimal benefit to the patients.

Hydrogen recombiner development at AECL

International Nuclear Information System (INIS)

Dewit, W.A.; Koroll, G.W.; Loesel Sitar, J.; Graham, W.R.C.

1997-01-01

Catalytic recombiners have been developed at AECL for the purpose of hydrogen removal in post-accident nuclear containment buildings. The recombiners are based on a particular catalyst designed by AECL which has extraordinary resistance to fouling from water and water vapour and a large thermodynamic range of operation. The catalysts were developed, originally, for the purpose of heavy water manufacturing by way of a catalytic exchange process. Application of these catalyst materials in recombiners for containment applications began in the late 1980's. The first application was a passive recombiner, qualified for use in control of radiolytic hydrogen in the headspace of a pool-type experimental reactor of AECL design in 1988. The passive, or natural convection recombiner concept has continued development to commercial stage for application in power reactor containments. This paper reviews the AECL recombiner development, describes the current model and shows results from tests of full-scale recombiners in the Large Scale Vented Combustion Test Facility at AECL-WL. The AECL recombiner is designed for compactness and ease of engineering into containment. The design is a simple, open-ended rectangular enclosure with catalyst elements arranged inside to promote optimum convective flow driven by heat of recombination at the catalyst surface. Self start, as evidenced by catalyst heating and initiation of flow, is achieved in less than 1% hydrogen, with available oxygen, at room temperature and 100% relative humidity. This low temperature start-up in condensing atmospheres is viewed as the most challenging condition for wet-proofing effectiveness. Cold start-up is a vital performance requirement in containments, such as CANDU, where engineered air-cooling systems are operating and where long-term hydrogen control is required, after containment atmospheres have cooled. Once started, the removal capacity scales linearly with the inlet cross-section area and the partial

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

Science.gov (United States)

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.

Effects of nuclear mutations for recombination and repair functions and of caffeine on mitochondrial recombination

International Nuclear Information System (INIS)

Fraenkel, A.H.M.

1974-01-01

Studies of both prokaryotic and eukaryotic organisms indicate that pathways governing repair of damage to nuclear DNA caused by x-ray or ultraviolet irradiation overlap with those controlling recombination. Fourteen nuclear mutants of Saccharomyces cerevisiae were tested in order to determine whether these mutant genes affected mitochondrial recombination. None of the mutations studied significantly affected mitochondrial recombination. The nuclear recombination and repair pathways studied do not overlap with the nuclear pathway which controls recombination of mitochondrial DNA. A second set of experiments was designed to test the effect of caffeine on both nuclear and mitochondrial recombination in Saccharomyces cerevisiae. (U.S.)

Rational design of functional and tunable oscillating enzymatic networks

Science.gov (United States)

Semenov, Sergey N.; Wong, Albert S. Y.; van der Made, R. Martijn; Postma, Sjoerd G. J.; Groen, Joost; van Roekel, Hendrik W. H.; de Greef, Tom F. A.; Huck, Wilhelm T. S.

2015-02-01

Life is sustained by complex systems operating far from equilibrium and consisting of a multitude of enzymatic reaction networks. The operating principles of biology's regulatory networks are known, but the in vitro assembly of out-of-equilibrium enzymatic reaction networks has proved challenging, limiting the development of synthetic systems showing autonomous behaviour. Here, we present a strategy for the rational design of programmable functional reaction networks that exhibit dynamic behaviour. We demonstrate that a network built around autoactivation and delayed negative feedback of the enzyme trypsin is capable of producing sustained oscillating concentrations of active trypsin for over 65 h. Other functions, such as amplification, analog-to-digital conversion and periodic control over equilibrium systems, are obtained by linking multiple network modules in microfluidic flow reactors. The methodology developed here provides a general framework to construct dissipative, tunable and robust (bio)chemical reaction networks.

Testing the rationality assumption using a design difference in the TV game show 'Jeopardy'

OpenAIRE

Sjögren Lindquist, Gabriella; Säve-Söderbergh, Jenny

2006-01-01

Abstract This paper empirically investigates the rationality assumption commonly applied in economic modeling by exploiting a design difference in the game-show Jeopardy between the US and Sweden. In particular we address the assumption of individuals’ capabilities to process complex mathematical problems to find optimal strategies. The vital difference is that US contestants are given explicit information before they act, while Swedish contestants individually need to calculate the same info...

MODEST: a web-based design tool for oligonucleotide-mediated genome engineering and recombineering

DEFF Research Database (Denmark)

Bonde, Mads; Klausen, Michael Schantz; Anderson, Mads Valdemar

2014-01-01

Recombineering and multiplex automated genome engineering (MAGE) offer the possibility to rapidly modify multiple genomic or plasmid sites at high efficiencies. This enables efficient creation of genetic variants including both single mutants with specifically targeted modifications as well......, which confers the corresponding genetic change, is performed manually. To address these challenges, we have developed the MAGE Oligo Design Tool (MODEST). This web-based tool allows designing of MAGE oligos for (i) tuning translation rates by modifying the ribosomal binding site, (ii) generating...

Virus-Like Particle Engineering: From Rational Design to Versatile Applications.

Science.gov (United States)

Ding, Xuanwei; Liu, Dong; Booth, George; Gao, Wei; Lu, Yuan

2018-05-01

As mimicking natural virus structures, virus-like particles (VLPs) have evolved to become a widely accepted technology used for humans which are safe, highly efficacious, and profitable. Several remarkable advantages have been achieved to revolutionize the molecule delivery for diverse applications in nanotechnology, biotechnology, and medicine. Here, the rational structure design, manufacturing process, functionalization strategy, and emerging applications of VLPs is reviewed. The situation and challenges in the VLP engineering, the key development orientation, and future applications have been discussed. To develop a good VLP design concept, the virus/VLP-host interactions need to be examined and the screening methods of the VLP stabilization factors need to be established. The functionalization toolbox can be expanded to fabricate smart, robust, and multifunctional VLPs. Novel robust VLP manufacturing platforms are required to deliver vaccines in resource-poor regions with a significant reduction in the production time and cost. The future applications of VLPs are always driven by the development of emerging technologies and new requirements of modern life. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rationality of limited rationality : some aggregate implications

OpenAIRE

Uri M. Possen; Mikko Puhakka

1994-01-01

In this paper we let economic agents choose whether to become fully rational or stay boundedly rational. Boundedly rational agents are less sophisticated in their information processing abilities. It is costly to acquire information needed to become fully rational, and thus not all agents are willing to incur those costs. We then explore the aggregate effects of endogenizing the decision whether the agent should or should not become fully rational in handling information. Since fully and boun...

Rationalization with ruled surfaces in architecture

DEFF Research Database (Denmark)

Steenstrup, Kasper Hornbak

This thesis addresses the problems of rationalizing and segmenting large scale 3D models, and how to handle difficult production constraints in this area. The design choices when constructing large scale architecture are influenced by the budget. Therefore I strive to minimize the amount of time...... and material needed for production. This makes advanced free form architecture viable for low cost projects, allowing the architects to realize their designs. By pre-cutting building blocks using hot wire robots, the amount of milling necessary can be reduced drastically. I do this by rationalizing...

GREEN: A program package for docking studies in rational drug design

Science.gov (United States)

Tomioka, Nobuo; Itai, Akiko

1994-08-01

A program package, GREEN, has been developed that enables docking studies between ligand molecules and a protein molecule. Based on the structure of the protein molecule, the physical and chemical environment of the ligand-binding site is expressed as three-dimensional grid-point data. The grid-point data are used for the real-time evaluation of the protein-ligand interaction energy, as well as for the graphical representation of the binding-site environment. The interactive docking operation is facilitated by various built-in functions, such as energy minimization, energy contribution analysis and logging of the manipulation trajectory. Interactive modeling functions are incorporated for designing new ligand molecules while considering the binding-site environment and the protein-ligand interaction. As an example of the application of GREEN, a docking study is presented on the complex between trypsin and a synthetic trypsin inhibitor. The program package will be useful for rational drug design, based on the 3D structure of the target protein.

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

Directory of Open Access Journals (Sweden)

Ieva Migliniene

2017-12-01

Full Text Available 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.

Rationalization and Design of the Complementarity Determining Region Sequences in an Antibody-Antigen Recognition Interface

Science.gov (United States)

Chen, Ing-Chien; Lee, Yu-Ching; Chen, Jun-Bo; Tsai, Keng-Chang; Chen, Ching-Tai; Chang, Jeng-Yih; Yang, Ei-Wen; Hsu, Po-Chiang; Jian, Jhih-Wei; Hsu, Hung-Ju; Chang, Hung-Ju; Hsu, Wen-Lian; Huang, Kai-Fa; Ma, Alex Che; Yang, An-Suei

2012-01-01

Protein-protein interactions are critical determinants in biological systems. Engineered proteins binding to specific areas on protein surfaces could lead to therapeutics or diagnostics for treating diseases in humans. But designing epitope-specific protein-protein interactions with computational atomistic interaction free energy remains a difficult challenge. Here we show that, with the antibody-VEGF (vascular endothelial growth factor) interaction as a model system, the experimentally observed amino acid preferences in the antibody-antigen interface can be rationalized with 3-dimensional distributions of interacting atoms derived from the database of protein structures. Machine learning models established on the rationalization can be generalized to design amino acid preferences in antibody-antigen interfaces, for which the experimental validations are tractable with current high throughput synthetic antibody display technologies. Leave-one-out cross validation on the benchmark system yielded the accuracy, precision, recall (sensitivity) and specificity of the overall binary predictions to be 0.69, 0.45, 0.63, and 0.71 respectively, and the overall Matthews correlation coefficient of the 20 amino acid types in the 24 interface CDR positions was 0.312. The structure-based computational antibody design methodology was further tested with other antibodies binding to VEGF. The results indicate that the methodology could provide alternatives to the current antibody technologies based on animal immune systems in engineering therapeutic and diagnostic antibodies against predetermined antigen epitopes. PMID:22457753

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

Science.gov (United States)

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 of Coordination Polymers with Flexible Oxyethylene Side Chains

International Nuclear Information System (INIS)

Choi, Eun Young; Gao, Chunji; Lee, Suck Hyun; Kwon, O Pil

2012-01-01

We rationally designed and synthesized metallopolymers with organic 1,4-benzenedicarboxylic acid (BDC) linkers with different lengths of oxyethylene side chains in order to examine the influence of side chains on the coordination characteristics. While in a previous report the BDC linkers with alkyl side chains were found to form three-dimensional (3D) isoreticular metal-organic framework (IRMOF) structures or one-dimensional (1D) coordination polymeric structures with short -O(CH 2 ) 6 CH 3 or long -O(CH 2 ) 9 CH 3 side chains, respectively, new BDC linkers with oxyethylene side chains of the same lengths, -(OCH 2 CH 2 ) 2 CH 3 and -(OCH 2 CH 2 ) 3 CH 3 , form only 3D IRMOF structures. This result is attributed to the higher flexibility and smaller volume of oxyethylene side chains compared to alkyl side chains

Designer genes. Recombinant antibody fragments for biological imaging

Energy Technology Data Exchange (ETDEWEB)

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

2000-09-01

Monoclonal antibodies (MAbs), with high specificity and high affinity for their target antigens, can be utilized for delivery of agents such as radionuclides, enzymes, drugs or toxins in vivo. However, the implementation of radiolabeled antibodies as magic bullets for detection and treatment of diseases such as cancer has required addressing several shortcomings of murine MAbs. These include their immunogenicity, sub-optimal targeting and pharmacokinetic properties, and practical issues of production and radiolabeling. Genetic engineering provides a powerful approach for redesigning antibodies for use in oncologic applications in vivo. Recombinant fragments have been produced that retain high affinity for target antigens, and display a combination of rapid, high-level tumor targeting with concomitant clearance from normal tissues and the circulation in animal models. An important first step was cloning and engineering of antibody heavy and light chain variable domains into single-chain Fvs (molecular weight, 25-17 kDa), in which the variable regions are joined via a synthetic linker peptide sequence. Although scFvs themselves showed limited tumor uptake in preclinical and clinical studies, they provide a useful building block for intermediate sized recombinant fragments. Covalently linked dimers or non-covalent dimers of scFvs (also known as diabodies) show improved targeting and clearance properties due to their higher molecular weight (55kDa) and increased avidity. Further gains can be made by generation of larger recombinant fragments, such as the minibody, an scFv-C{sub H}3 fusion protein that self-assembles into a bivalent dimer of 80 kDa. A systematic evaluation of scFv, diabody, minibody, and intact antibody (based on comparison of tumor uptakes, tumor: blood activity ratios, and calculation of an Imaging Figure of Merit) can form the basis for selection of combinations of recombinant fragments and radionuclides for imaging applications. Ease of engineering

Designer genes. Recombinant antibody fragments for biological imaging

International Nuclear Information System (INIS)

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

2000-01-01

Monoclonal antibodies (MAbs), with high specificy and high affinity for their target antigens, can be utilized for delivery of agents such as radionuclides, enzymes, drugs or toxins in vivo. However, the implementation of radiolabeled antibodies as magic bullets for detection and treatment of diseases such as cancer has required addressing several shortcomings of murine MAbs. These include their immunogenicity, sub-optimal targeting and pharmacokinetic properties, and practical issues of production and radiolabeling. Genetic engineering provides a powerful approach for redesigning antibodies for use in oncologic applications in vivo. Recombinant fragments have been produced that retain high affinity for target antigens, and display a combination of rapid, high-level tumor targeting with concomitant clearance from normal tissues and the circulation in animal models. An important first step was cloning and engineering of antibody heavy and light chain variable domains into single-chain Fvs (molecular weight, 25-17 kDa), in which the variable regions are joined via a synthetic linker peptide sequence. Although scFvs themselves showed limited tumor uptake in preclinical and clinical studies, they provide a useful building block for intermediate sized recombinant fragments. Covalently linked dimers or non-covalent dimers of scFvs (also known as diabodies) show improved targeting and clearance properties due to their higher molecular weight (55kDa) and increased avidity. Further gains can be made by generation of larger recombinant fragments, such as the minibody, an scFv-C H 3 fusion protein that self-assembles into a bivalent dimer of 80 kDa. A systematic evaluation of scFv, diabody, minibody, and intact antibody (based on comparison of tumor uptakes, tumor: blood activity ratios, and calculation of an Imaging Figure of Merit) can form the basis for selection of combinations of recombinant fragments and radionuclides for imaging applications. Ease of engineering and

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

Science.gov (United States)

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

2005-05-01

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

Improving specific activity and thermostability of Escherichia coli phytase by structure-based rational design.

Science.gov (United States)

Wu, Tzu-Hui; Chen, Chun-Chi; Cheng, Ya-Shan; Ko, Tzu-Ping; Lin, Cheng-Yen; Lai, Hui-Lin; Huang, Ting-Yung; Liu, Je-Ruei; Guo, Rey-Ting

2014-04-10

Escherichia coli phytase (EcAppA) which hydrolyzes phytate has been widely applied in the feed industry, but the need to improve the enzyme activity and thermostability remains. Here, we conduct rational design with two strategies to enhance the EcAppA performance. First, residues near the substrate binding pocket of EcAppA were modified according to the consensus sequence of two highly active Citrobacter phytases. One out of the eleven mutants, V89T, exhibited 17.5% increase in catalytic activity, which might be a result of stabilized protein folding. Second, the EcAppA glycosylation pattern was modified in accordance with the Citrobacter phytases. An N-glycosylation motif near the substrate binding site was disrupted to remove spatial hindrance for phytate entry and product departure. The de-glycosylated mutants showed 9.6% increase in specific activity. On the other hand, the EcAppA mutants that adopt N-glycosylation motifs from CbAppA showed improved thermostability that three mutants carrying single N-glycosylation motif exhibited 5.6-9.5% residual activity after treatment at 80°C (1.8% for wild type). Furthermore, the mutant carrying all three glycosylation motifs exhibited 27% residual activity. In conclusion, a successful rational design was performed to obtain several useful EcAppA mutants with better properties for further applications. Copyright © 2014 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

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

2013-11-01

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

Chemical engineering in the electronics industry: progress towards the rational design of organic semiconductor heterojunctions

KAUST Repository

Clancy, Paulette

2012-05-01

We review the current status of heterojunction design for combinations of organic semiconductor materials, given its central role in affecting the device performance for electronic devices and solar cell applications. We provide an emphasis on recent progress towards the rational design of heterojunctions that may lead to higher performance of charge separation and mobility. We also play particular attention to the role played by computational approaches and its potential to help define the best choice of materials for solar cell development in the future. We report the current status of the field with respect to such goals. © 2012 Elsevier Ltd.

Chemical engineering in the electronics industry: progress towards the rational design of organic semiconductor heterojunctions

KAUST Repository

Clancy, Paulette

2012-01-01

We review the current status of heterojunction design for combinations of organic semiconductor materials, given its central role in affecting the device performance for electronic devices and solar cell applications. We provide an emphasis on recent progress towards the rational design of heterojunctions that may lead to higher performance of charge separation and mobility. We also play particular attention to the role played by computational approaches and its potential to help define the best choice of materials for solar cell development in the future. We report the current status of the field with respect to such goals. © 2012 Elsevier Ltd.

Rational development of an attenuated recombinant cyprinid herpesvirus 3 vaccine using prokaryotic mutagenesis and in vivo bioluminescent imaging

Science.gov (United States)

Cyprinid herpesvirus 3 (CyHV-3) is causing severe economic losses worldwide in the carp industry, and a safe and efficacious attenuated vaccine compatible with mass vaccination is needed. We produced single deleted recombinants using prokaryotic mutagenesis. When producing a recombinant lacking open...

Theory and simulation of DNA-coated colloids: a guide for rational design.

Science.gov (United States)

Angioletti-Uberti, Stefano; Mognetti, Bortolo M; Frenkel, Daan

2016-03-07

By exploiting the exquisite selectivity of DNA hybridization, DNA-coated colloids (DNACCs) can be made to self-assemble in a wide variety of structures. The beauty of this system stems largely from its exceptional versatility and from the fact that a proper choice of the grafted DNA sequences yields fine control over the colloidal interactions. Theory and simulations have an important role to play in the optimal design of self assembling DNACCs. At present, the powerful model-based design tools are not widely used, because the theoretical literature is fragmented and the connection between different theories is often not evident. In this Perspective, we aim to discuss the similarities and differences between the different models that have been described in the literature, their underlying assumptions, their strengths and their weaknesses. Using the tools described in the present Review, it should be possible to move towards a more rational design of novel self-assembling structures of DNACCs and, more generally, of systems where ligand-receptor are used to control interactions.

Rational In Silico Design of an Organic Semiconductor with Improved Electron Mobility.

Science.gov (United States)

Friederich, Pascal; Gómez, Verónica; Sprau, Christian; Meded, Velimir; Strunk, Timo; Jenne, Michael; Magri, Andrea; Symalla, Franz; Colsmann, Alexander; Ruben, Mario; Wenzel, Wolfgang

2017-11-01

Organic semiconductors find a wide range of applications, such as in organic light emitting diodes, organic solar cells, and organic field effect transistors. One of their most striking disadvantages in comparison to crystalline inorganic semiconductors is their low charge-carrier mobility, which manifests itself in major device constraints such as limited photoactive layer thicknesses. Trial-and-error attempts to increase charge-carrier mobility are impeded by the complex interplay of the molecular and electronic structure of the material with its morphology. Here, the viability of a multiscale simulation approach to rationally design materials with improved electron mobility is demonstrated. Starting from one of the most widely used electron conducting materials (Alq 3 ), novel organic semiconductors with tailored electronic properties are designed for which an improvement of the electron mobility by three orders of magnitude is predicted and experimentally confirmed. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Design of a Discrete Tracking Controller for a Magnetic Levitation System: A Nonlinear Rational Model Approach

Directory of Open Access Journals (Sweden)

Fernando Gómez-Salas

2015-01-01

Full Text Available This work proposes a discrete-time nonlinear rational approximate model for the unstable magnetic levitation system. Based on this model and as an application of the input-output linearization technique, a discrete-time tracking control design will be derived using the corresponding classical state space representation of the model. A simulation example illustrates the efficiency of the proposed methodology.

Rational design of a bi-layered reduced graphene oxide film on polystyrene foam for solar-driven interfacial water evaporation

KAUST Repository

Shi, Le; Wang, Yuchao; Zhang, Lianbin; Wang, Peng

2016-01-01

Solar-driven water evaporation has been emerging as a highly efficient way for utilizing solar energy for clean water production and wastewater treatment. Here we rationally designed and fabricated a bi-layered photothermal membrane with a porous

Rational Design, Synthesis and Pharmacological Evaluation of the (2R)- and (2S)-Stereoisomers of 3-(2-Carboxypyrrolidinyl)-2-methyl Acetic Acid as Ligands for the Ionotropic Glutamate Receptors

DEFF Research Database (Denmark)

Rasmussen, Julie; Storgaard, Morten; Pickering, Darryl S

2011-01-01

In this paper we describe the rational design, synthesis and pharmacological evaluation of two new stereoisomeric (S)-glutamate (Glu) analogues. The rational design was based on hybrid structures of the natural product kainic acid, a synthetic analogue CPAA and the high-affinity Glu analogue SYM...

Rational design of stealthy hyperuniform two-phase media with tunable order

Science.gov (United States)

DiStasio, Robert A.; Zhang, Ge; Stillinger, Frank H.; Torquato, Salvatore

2018-02-01

Disordered stealthy hyperuniform materials are exotic amorphous states of matter that have attracted recent attention because of their novel structural characteristics (hidden order at large length scales) and physical properties, including desirable photonic and transport properties. It is therefore useful to devise algorithms that enable one to design a wide class of such amorphous configurations at will. In this paper, we present several algorithms enabling the systematic identification and generation of discrete (digitized) stealthy hyperuniform patterns with a tunable degree of order, paving the way towards the rational design of disordered materials endowed with novel thermodynamic and physical properties. To quantify the degree of order or disorder of the stealthy systems, we utilize the discrete version of the τ order metric, which accounts for the underlying spatial correlations that exist across all relevant length scales in a given digitized two-phase (or, equivalently, a two-spin state) system of interest. Our results impinge on a myriad of fields, ranging from physics, materials science and engineering, visual perception, and information theory to modern data science.

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

Science.gov (United States)

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

Rationalization: A Bibliography.

Science.gov (United States)

Pedrini, D. T.; Pedrini, Bonnie C.

Rationalization was studied by Sigmund Freud and was specifically labeled by Ernest Jones. Rationalization ought to be differentiated from rational, rationality, logical analysis, etc. On the one hand, rationalization is considered a defense mechanism, on the other hand, rationality is not. Haan has done much work with self-report inventories and…

Public policy, rationality and reason

Directory of Open Access Journals (Sweden)

Rodolfo Canto Sáenz

2015-07-01

Full Text Available This work suggests the incorporation of practical reason in the design, implementation and evaluation of public policies, alongside instrumental rationality. It takes two proposals that today point in this direction: Rawls distinction between reasonable (practical reason and rational (instrumental reason and what this author calls the CI Procedure (categorical imperative procedure and Habermas model of deliberative democracy. The main conclusion is that the analysis of public policies can not be limited to rather narrow limits of science, but requires the contribution of political and moral philosophy.

Rational Design and Synthesis of Efficient Sunscreens To Boost the Solar Protection Factor.

Science.gov (United States)

Losantos, Raúl; Funes-Ardoiz, Ignacio; Aguilera, José; Herrera-Ceballos, Enrique; García-Iriepa, Cristina; Campos, Pedro J; Sampedro, Diego

2017-03-01

Skin cancer incidence has been increasing in the last decades, but most of the commercial formulations used as sunscreens are designed to protect only against solar erythema. Many of the active components present in sunscreens show critical weaknesses, such as low stability and toxicity. Thus, the development of more efficient components is an urgent health necessity and an attractive industrial target. We have rationally designed core moieties with increased photoprotective capacities and a new energy dissipation mechanism. Using these scaffolds, we have synthesized a series of compounds with tunable properties suitable for their use in sunscreens, and enhanced properties in terms of stability, light energy dissipation, and toxicity. Moreover, some representative compounds were included in final sunscreen formulations and a relevant solar protection factor boost was measured. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rational Decision Making as Performative Praxis: Explaining Rationality's Éternel Retour

OpenAIRE

Cabantous, L.; Gond, J-P.

2011-01-01

Organizational theorists built their knowledge of decision making through a progressive critique of rational choice theory. Their positioning towards rationality, however, is at odds with the observation of rationality persistence in organizational life. This paper addresses this paradox. It proposes a new perspective on rationality that allows the theorizing of the production of rational decisions by organizations. To account for rationality's éternel retour, we approach rational decision ma...

Rational design of gene-based vaccines.

Science.gov (United States)

Barouch, Dan H

2006-01-01

Vaccine development has traditionally been an empirical discipline. Classical vaccine strategies include the development of attenuated organisms, whole killed organisms, and protein subunits, followed by empirical optimization and iterative improvements. While these strategies have been remarkably successful for a wide variety of viruses and bacteria, these approaches have proven more limited for pathogens that require cellular immune responses for their control. In this review, current strategies to develop and optimize gene-based vaccines are described, with an emphasis on novel approaches to improve plasmid DNA vaccines and recombinant adenovirus vector-based vaccines. Copyright 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Rational Design of a Green-Light-Mediated Unimolecular Platform for Fast Switchable Acidic Sensing.

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Rational design of diagnostic and vaccination strategies for tuberculosis

Directory of Open Access Journals (Sweden)

Sibele Borsuk

Full Text Available The development of diagnostic tests which can readily differentiate between vaccinated and tuberculosis-infected individuals is crucial for the wider utilization of bacillus Calmette-Guérin (BCG as vaccine in humans and animals. BCG_0092 is an antigen that elicits specific delayed type hypersensitivity reactions similar in size and morphological aspects to that elicited by purified protein derivative, in both animals and humans infected with the tubercle bacilli. We carried out bioinformatics analyses of the BCG_0092 and designed a diagnostic test by using the predicted MHC class I epitopes. In addition, we performed a knockout of this gene by homologous recombination in the BCG vaccine strain to allow differentiation of vaccinated from infected individuals. For that, the flanking sequences of the target gene (BCG_0092were cloned into a suicide vector. Spontaneous double crossovers, which result in wild type revertants or knockouts were selected using SacB. BCG_0092 is present only in members of the Mycobacterium tuberculosis complex. Eight predicted MHC class I epitopes with potential for immunological diagnosis were defined, allowing the design of a specific diagnostic test. The strategy used to delete the (BCG_0092 gene from BCG was successful. The knockout genotype was confirmed by PCR and by Southern blot. The mutant BCG strain has the potential of inducing protection against tuberculosis without interfering with the diagnostic test based on the use of selected epitopes from BCG_0092.

Laccase engineering: from rational design to directed evolution.

Science.gov (United States)

Mate, Diana M; Alcalde, Miguel

2015-01-01

Laccases are multicopper oxidoreductases considered by many in the biotechonology field as the ultimate "green catalysts". This is mainly due to their broad substrate specificity and relative autonomy (they use molecular oxygen from air as an electron acceptor and they only produce water as by-product), making them suitable for a wide array of applications: biofuel production, bioremediation, organic synthesis, pulp biobleaching, textiles, the beverage and food industries, biosensor and biofuel cell development. Since the beginning of the 21st century, specific features of bacterial and fungal laccases have been exhaustively adapted in order to reach the industrial demands for high catalytic activity and stability in conjunction with reduced production cost. Among the goals established for laccase engineering, heterologous functional expression, improved activity and thermostability, tolerance to non-natural media (organic solvents, ionic liquids, physiological fluids) and resistance to different types of inhibitors are all challenges that have been met, while obtaining a more comprehensive understanding of laccase structure-function relationships. In this review we examine the most significant advances in this exciting research area in which rational, semi-rational and directed evolution approaches have been employed to ultimately convert laccases into high value-added biocatalysts. Copyright © 2014 Elsevier Inc. All rights reserved.

The use of 'Omics technology to rationally improve industrial mammalian cell line performance.

Science.gov (United States)

Lewis, Amanda M; Abu-Absi, Nicholas R; Borys, Michael C; Li, Zheng Jian

2016-01-01

Biologics represent an increasingly important class of therapeutics, with 7 of the 10 top selling drugs from 2013 being in this class. Furthermore, health authority approval of biologics in the immuno-oncology space is expected to transform treatment of patients with debilitating and deadly diseases. The growing importance of biologics in the healthcare field has also resulted in the recent approvals of several biosimilars. These recent developments, combined with pressure to provide treatments at lower costs to payers, are resulting in increasing need for the industry to quickly and efficiently develop high yielding, robust processes for the manufacture of biologics with the ability to control quality attributes within narrow distributions. Achieving this level of manufacturing efficiency and the ability to design processes capable of regulating growth, death and other cellular pathways through manipulation of media, feeding strategies, and other process parameters will undoubtedly be facilitated through systems biology tools generated in academic and public research communities. Here we discuss the intersection of systems biology, 'Omics technologies, and mammalian bioprocess sciences. Specifically, we address how these methods in conjunction with traditional monitoring techniques represent a unique opportunity to better characterize and understand host cell culture state, shift from an empirical to rational approach to process development and optimization of bioreactor cultivation processes. We summarize the following six key areas: (i) research applied to parental, non-recombinant cell lines; (ii) systems level datasets generated with recombinant cell lines; (iii) datasets linking phenotypic traits to relevant biomarkers; (iv) data depositories and bioinformatics tools; (v) in silico model development, and (vi) examples where these approaches have been used to rationally improve cellular processes. We critically assess relevant and state of the art research

Design of charge exchange recombination spectroscopy for the joint Texas experimental tokamak

Energy Technology Data Exchange (ETDEWEB)

Chi, Y.; Zhuang, G., E-mail: ge-zhuang@hust.edu.cn; Cheng, Z. F.; Hou, S. Y.; Cheng, C.; Li, Z.; Wang, J. R.; Wang, Z. J. [State Key Laboratory of Advanced Electromagnetic Engineering and Technology, Huazhong University of Science and Technology, Wuhan 430074 (China)

2014-11-15

The old diagnostic neutral beam injector first operated at the University of Texas at Austin is ready for rejoining the joint Texas experimental tokamak (J-TEXT). A new set of high voltage power supplies has been equipped and there is no limitation for beam modulation or beam pulse duration henceforth. Based on the spectra of fully striped impurity ions induced by the diagnostic beam the design work for toroidal charge exchange recombination spectroscopy (CXRS) system is presented. The 529 nm carbon VI (n = 8 − 7 transition) line seems to be the best choice for ion temperature and plasma rotation measurements and the considered hardware is listed. The design work of the toroidal CXRS system is guided by essential simulation of expected spectral results under the J-TEXT tokamak operation conditions.

Rationality in Society

NARCIS (Netherlands)

Flache, Andreas; Dijkstra, Jacob; Wright, James D.

2015-01-01

Contemporary theories of rational behavior in human society augment the orthodox model of rationality both by adding various forms of bounded rationality and relaxing the assumptions of self-interest and materialistic preferences. This entry discusses how these extensions of the theory of rational

A Rational Approach to Rational Suicide.

Science.gov (United States)

Richman, Joseph

1992-01-01

Describes suicide as reaction to internal and external sources of stress and the impact of life events. Notes that, in the elderly, these situations are prevalent in many who are not suicidal. Contends that much more is written about rational suicide than its alternative (rational nonsuicide). Reviews reasons for this and suggests rational…

Rational design of competitive electrocatalysts for the oxygen reduction reaction in hydrogen fuel cells

Science.gov (United States)

Stolbov, Sergey; Alcántara Ortigoza, Marisol

2012-02-01

The large-scale application of one of the most promising clean and renewable sources of energy, hydrogen fuel cells, still awaits efficient and cost-effective electrocatalysts for the oxygen reduction reaction (ORR) occurring on the cathode. We demonstrate that truly rational design renders electrocatalysts possessing both qualities. By unifying the knowledge on surface morphology, composition, electronic structure and reactivity, we solve that sandwich-like structures are an excellent choice for optimization. Their constituting species couple synergistically yielding reaction-environment stability, cost-effectiveness and tunable reactivity. This cooperative-action concept enabled us to predict two advantageous ORR electrocatalysts. Density functional theory calculations of the reaction free-energy diagrams confirm that these materials are more active toward ORR than the so far best Pt-based catalysts. Our designing concept advances also a general approach for engineering materials in heterogeneous catalysis.

Plasmonic Solar Cells: From Rational Design to Mechanism Overview.

Science.gov (United States)

Jang, Yoon Hee; Jang, Yu Jin; Kim, Seokhyoung; Quan, Li Na; Chung, Kyungwha; Kim, Dong Ha

2016-12-28

Plasmonic effects have been proposed as a solution to overcome the limited light absorption in thin-film photovoltaic devices, and various types of plasmonic solar cells have been developed. This review provides a comprehensive overview of the state-of-the-art progress on the design and fabrication of plasmonic solar cells and their enhancement mechanism. The working principle is first addressed in terms of the combined effects of plasmon decay, scattering, near-field enhancement, and plasmonic energy transfer, including direct hot electron transfer and resonant energy transfer. Then, we summarize recent developments for various types of plasmonic solar cells based on silicon, dye-sensitized, organic photovoltaic, and other types of solar cells, including quantum dot and perovskite variants. We also address several issues regarding the limitations of plasmonic nanostructures, including their electrical, chemical, and physical stability, charge recombination, narrowband absorption, and high cost. Next, we propose a few potentially useful approaches that can improve the performance of plasmonic cells, such as the inclusion of graphene plasmonics, plasmon-upconversion coupling, and coupling between fluorescence resonance energy transfer and plasmon resonance energy transfer. This review is concluded with remarks on future prospects for plasmonic solar cell use.

Geometric Rationalization for Freeform Architecture

KAUST Repository

Jiang, Caigui

2016-06-20

The emergence of freeform architecture provides interesting geometric challenges with regards to the design and manufacturing of large-scale structures. To design these architectural structures, we have to consider two types of constraints. First, aesthetic constraints are important because the buildings have to be visually impressive. Sec- ond, functional constraints are important for the performance of a building and its e cient construction. This thesis contributes to the area of architectural geometry. Specifically, we are interested in the geometric rationalization of freeform architec- ture with the goal of combining aesthetic and functional constraints and construction requirements. Aesthetic requirements typically come from designers and architects. To obtain visually pleasing structures, they favor smoothness of the building shape, but also smoothness of the visible patterns on the surface. Functional requirements typically come from the engineers involved in the construction process. For exam- ple, covering freeform structures using planar panels is much cheaper than using non-planar ones. Further, constructed buildings have to be stable and should not collapse. In this thesis, we explore the geometric rationalization of freeform archi- tecture using four specific example problems inspired by real life applications. We achieve our results by developing optimization algorithms and a theoretical study of the underlying geometrical structure of the problems. The four example problems are the following: (1) The design of shading and lighting systems which are torsion-free structures with planar beams based on quad meshes. They satisfy the functionality requirements of preventing light from going inside a building as shad- ing systems or reflecting light into a building as lighting systems. (2) The Design of freeform honeycomb structures that are constructed based on hex-dominant meshes with a planar beam mounted along each edge. The beams intersect without

Construction and biological characterization of artificial recombinants between a wild type flavivirus (Kunjin) and a live chimeric flavivirus vaccine (ChimeriVax-JE).

Science.gov (United States)

Pugachev, Konstantin V; Schwaiger, Julia; Brown, Nathan; Zhang, Zhen-xi; Catalan, John; Mitchell, Frederick S; Ocran, Simeon W; Rumyantsev, Alexander A; Khromykh, Alexander A; Monath, Thomas P; Guirakhoo, Farshad

2007-09-17

Although the theoretical concern of genetic recombination has been raised related to the use of live attenuated flavivirus vaccines [Seligman, Gould, Lancet 2004;363:2073-5], it has little foundation [e.g., Monath TP, Kanesa-Thasan N, Guirakhoo F, Pugachev K, Almond J, Lang J, et al. Vaccine 2005;23:2956-8]. To investigate biological effects of recombination between a chimeric yellow fever (YF) 17D/Japanese encephalitis (JE) vaccine virus (ChimeriVax-JE) and a wild-type flavivirus Kunjin (KUN-cDNA), the prM-E envelope protein genes were swapped between the two viruses, resulting in new YF 17D/KUN(prM-E) and KUN/JE(prM-E) chimeras. The prM-E genes are easily exchangeable between flavivirues, and thus the exchange was expected to yield the most replication-competent chimeras, while other rationally designed recombinants would be more likely to be crippled or non-viable. The new chimeras proved highly attenuated in comparison with the KUN-cDNA parent, as judged by plaque size and growth kinetics in cell culture, low viremia in hamsters, and reduced neurovirulence/neuroinvasiveness in mice. These data provide strong experimental evidence that the potential of recombinants, should they ever emerge, to cause disease or spread (compete in nature with wild-type flaviviruses) would be indeed extremely low.

Guidelines for Rational Cancer Therapeutics

Directory of Open Access Journals (Sweden)

Byunghee Yoo

2017-12-01

Full Text Available Traditionally, cancer therapy has relied on surgery, radiation therapy, and chemotherapy. In recent years, these interventions have become increasingly replaced or complemented by more targeted approaches that are informed by a deeper understanding of the underlying biology. Still, the implementation of fully rational patient-specific drug design appears to be years away. Here, we present a vision of rational drug design for cancer that is defined by two major components: modularity and image guidance. We suggest that modularity can be achieved by combining a nanocarrier and an oligonucleotide component into the therapeutic. Image guidance can be incorporated into the nanocarrier component by labeling with a specific imaging reporter, such as a radionuclide or contrast agent for magnetic resonance imaging. While limited by the need for additional technological advancement in the areas of cancer biology, nanotechnology, and imaging, this vision for the future of cancer therapy can be used as a guide to future research endeavors.

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

Science.gov (United States)

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.

Metabolite profiling of recombinant CHO cells: Designing tailored feeding regimes that enhance recombinant antibody production.

NARCIS (Netherlands)

Sellick, C.A.; Croxford, A.S.; Maqsood, A.R.; Stephens, G.; Westerhoff, H.V.; Goodacre, R.; Dickson, A.J.

2011-01-01

Chinese hamster ovary (CHO) cells are the primary platform for commercial expression of recombinant therapeutic proteins. Obtaining maximum production from the expression platform requires optimal cell culture medium (and associated nutrient feeds). We have used metabolite profiling to define the

Metabolite profiling of recombinant CHO cells: designing tailored feeding regimes that enhance recombinant antibody production.

NARCIS (Netherlands)

Sellick, C.A.; Croxford, A.S.; Maqsood, A.R.; Stephens, G.; Westerhoff, H.V.; Goodacre, R.; Dickson, A.J.

2011-01-01

Chinese hamster ovary (CHO) cells are the primary platform for commercial expression of recombinant therapeutic proteins. Obtaining maximum production from the expression platform requires optimal cell culture medium (and associated nutrient feeds). We have used metabolite profiling to define the

A rational and economical seismic design of beam columns in steel frames

International Nuclear Information System (INIS)

Gupta, A.K.; Fang, S.-J.; Chu, S.-L.

1977-01-01

In the present study, a new rational procedure is used in which simultaneous variation in various response quantities is predicted. For designing the beam column section according to the AISC Manual of Steel Construction, one has to know the values of the axial force, the moment about x and y axes at the two ends, and the maximum moments about x, y axes near the center of the beam column, which altogether constitutes seven response quantities of interest for each beam column element. Normally, seven equivalent modes will be required to represent the response. However, by designing the two end sections and the intermediate section independently one can consider three equivalent modes for each section, thus simplifying the problem a great deal. An existing computer program is used for the implementation of the proposed method. Results for typical example problems have been presented. It is shown that savings up to 42% in the steel cross-sectional area can be obtained depending upon combination of various forces and moments. The propposed method is 'exact' within the existing assumptions of the SRSS (square root of the sum of the squares) or the double sum method

Rational design of botulinum neurotoxin A1 mutants with improved oxidative stability.

Science.gov (United States)

López de la Paz, Manuela; Scheps, Daniel; Jurk, Marcel; Hofmann, Fred; Frevert, Jürgen

2018-06-01

Botulinum neurotoxins (BoNTs) are the most potent toxic proteins to mankind known but applied in low doses trigger a localized muscle paralysis that is beneficial for the therapy of several neurological disorders and aesthetic treatment. The paralytic effect is generated by the enzymatic activity of the light chain (LC) that cleaves specifically one of the SNARE proteins responsible for neurotransmitter exocytosis. The activity of the LC in a BoNT-containing therapeutic can be compromised by denaturing agents present during manufacturing and/or in the cell. Stabilization of the LC by reducing vulnerability towards denaturants would thus be advantageous for the development of BoNT-based therapeutics. In this work, we focused on increasing the stability of LC of BoNT/A1 (LC/A1) towards oxidative stress. We tackled this task by rational design of mutations at cysteine and methionine LC/A1 sites. Designed mutants showed improved oxidative stability in vitro and equipotency to wildtype toxin in vivo. Our results suggest that suitable modification of the catalytic domain can lead to more stable BoNTs without impairing their therapeutic efficacy. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

Science.gov (United States)

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.

Rational design of peptide affinity ligands for the purification of therapeutic enzymes.

Science.gov (United States)

Trasatti, John P; Woo, James; Ladiwala, Asif; Cramer, Steven; Karande, Pankaj

2018-04-25

Non-mAb biologics represent a growing class of therapeutics under clinical development. Although affinity chromatography is a potentially attractive approach for purification, the development of platform technologies, such as Protein A for mAbs, has been challenging due to the inherent chemical and structural diversity of these molecules. Here, we present our studies on the rapid development of peptide affinity ligands for the purification of biologics using a prototypical enzyme therapeutic in clinical use. Employing a suite of de novo rational and combinatorial design strategies we designed and screened a library of peptides on microarray platforms for their ability to bind to the target with high affinity and selectivity in cell culture fluid. Lead peptides were evaluated on resin in batch conditions and compared with a commercially available resin to evaluate their efficacy. Two lead candidates identified from microarray studies provided high binding capacity to the target while demonstrating high selectivity against culture contaminants and product variants compared to a commercial resin system. These findings provide a proof-of-concept for developing affinity peptide-based bioseparations processes for a target biologic. Peptide affinity ligand design and screening approaches presented in this work can also be easily translated to other biologics of interest. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 2018. © 2018 American Institute of Chemical Engineers.

Bioinformatics and multiepitope DNA immunization to design rational snake antivenom.

Directory of Open Access Journals (Sweden)

Simon C Wagstaff

2006-06-01

Full Text Available Snake venom is a potentially lethal and complex mixture of hundreds of functionally diverse proteins that are difficult to purify and hence difficult to characterize. These difficulties have inhibited the development of toxin-targeted therapy, and conventional antivenom is still generated from the sera of horses or sheep immunized with whole venom. Although life-saving, antivenoms contain an immunoglobulin pool of unknown antigen specificity and known redundancy, which necessitates the delivery of large volumes of heterologous immunoglobulin to the envenomed victim, thus increasing the risk of anaphylactoid and serum sickness adverse effects. Here we exploit recent molecular sequence analysis and DNA immunization tools to design more rational toxin-targeted antivenom.We developed a novel bioinformatic strategy that identified sequences encoding immunogenic and structurally significant epitopes from an expressed sequence tag database of a venom gland cDNA library of Echis ocellatus, the most medically important viper in Africa. Focusing upon snake venom metalloproteinases (SVMPs that are responsible for the severe and frequently lethal hemorrhage in envenomed victims, we identified seven epitopes that we predicted would be represented in all isomers of this multimeric toxin and that we engineered into a single synthetic multiepitope DNA immunogen (epitope string. We compared the specificity and toxin-neutralizing efficacy of antiserum raised against the string to antisera raised against a single SVMP toxin (or domains or antiserum raised by conventional (whole venom immunization protocols. The SVMP string antiserum, as predicted in silico, contained antibody specificities to numerous SVMPs in E. ocellatus venom and venoms of several other African vipers. More significantly, the antiserum cross-specifically neutralized hemorrhage induced by E. ocellatus and Cerastes cerastes cerastes venoms.These data provide valuable sequence and structure

Pragmatics & rationality.

OpenAIRE

Allott, N. E.

2007-01-01

This thesis is about the reconciliation of realistic views of rationality with inferential-intentional theories of communication. Grice (1957 1975) argued that working out what a speaker meant by an utterance is a matter of inferring the speaker's intentions on the presumption that she is acting rationally. This is abductive inference: inference to the best explanation for the utterance. Thus an utterance both rationalises and causes the interpretation the hearer constructs. Human rationality...

SequenceLDhot: detecting recombination hotspots.

Science.gov (United States)

Fearnhead, Paul

2006-12-15

There is much local variation in recombination rates across the human genome--with the majority of recombination occurring in recombination hotspots--short regions of around approximately 2 kb in length that have much higher recombination rates than neighbouring regions. Knowledge of this local variation is important, e.g. in the design and analysis of association studies for disease genes. Population genetic data, such as that generated by the HapMap project, can be used to infer the location of these hotspots. We present a new, efficient and powerful method for detecting recombination hotspots from population data. We compare our method with four current methods for detecting hotspots. It is orders of magnitude quicker, and has greater power, than two related approaches. It appears to be more powerful than HotspotFisher, though less accurate at inferring the precise positions of the hotspot. It was also more powerful than LDhot in some situations: particularly for weaker hotspots (10-40 times the background rate) when SNP density is lower (maths.lancs.ac.uk/~fearnhea/Hotspot.

Generation of Modified Pestiviruses by Targeted Recombination

DEFF Research Database (Denmark)

Rasmussen, Thomas Bruun; Friis, Martin Barfred; Risager, Peter Christian

involves targeted modification of viral cDNA genomes, cloned within BACs, by Red/ET recombination-mediated mutagenesis in E.coli DH10B cells. Using recombination-mediated mutagenesis for the targeted design, the work can be expedited and focused in principal on any sequence within the viral genome...

Progress and Design Concerns of Nanostructured Solar Energy Harvesting Devices.

Science.gov (United States)

Leung, Siu-Fung; Zhang, Qianpeng; Tavakoli, Mohammad Mahdi; He, Jin; Mo, Xiaoliang; Fan, Zhiyong

2016-05-01

Integrating devices with nanostructures is considered a promising strategy to improve the performance of solar energy harvesting devices such as photovoltaic (PV) devices and photo-electrochemical (PEC) solar water splitting devices. Extensive efforts have been exerted to improve the power conversion efficiencies (PCE) of such devices by utilizing novel nanostructures to revolutionize device structural designs. The thicknesses of light absorber and material consumption can be substantially reduced because of light trapping with nanostructures. Meanwhile, the utilization of nanostructures can also result in more effective carrier collection by shortening the photogenerated carrier collection path length. Nevertheless, performance optimization of nanostructured solar energy harvesting devices requires a rational design of various aspects of the nanostructures, such as their shape, aspect ratio, periodicity, etc. Without this, the utilization of nanostructures can lead to compromised device performance as the incorporation of these structures can result in defects and additional carrier recombination. The design guidelines of solar energy harvesting devices are summarized, including thin film non-uniformity on nanostructures, surface recombination, parasitic absorption, and the importance of uniform distribution of photo-generated carriers. A systematic view of the design concerns will assist better understanding of device physics and benefit the fabrication of high performance devices in the future. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Baseline rationing

DEFF Research Database (Denmark)

Hougaard, Jens Leth; Moreno-Ternero, Juan D.; Østerdal, Lars Peter Raahave

The standard problem of adjudicating conflicting claims describes a situation in which a given amount of a divisible good has to be allocated among agents who hold claims against it exceeding the available amount. This paper considers more general rationing problems in which, in addition to claims...... to international protocols for the reduction of greenhouse emissions, or water distribution in drought periods. We define a family of allocation methods for such general rationing problems - called baseline rationing rules - and provide an axiomatic characterization for it. Any baseline rationing rule within...... the family is associated with a standard rule and we show that if the latter obeys some properties reflecting principles of impartiality, priority and solidarity, the former obeys them too....

Graded Recombination Layers for Multijunction Photovoltaics

KAUST Repository

Koleilat, Ghada I.

2012-06-13

Multijunction devices consist of a stack of semiconductor junctions having bandgaps tuned across a broad spectrum. In solar cells this concept is used to increase the efficiency of photovoltaic harvesting, while light emitters and detectors use it to achieve multicolor and spectrally tunable behavior. In series-connected current-matched multijunction devices, the recombination layers must allow the hole current from one cell to recombine, with high efficiency and low voltage loss, with the electron current from the next cell. We recently reported a tandem solar cell in which the recombination layer was implemented using a progression of n-type oxides whose doping densities and work functions serve to connect, with negligible resistive loss at solar current densities, the constituent cells. Here we present the generalized conditions for design of efficient graded recombination layer solar devices. We report the number of interlayers and the requirements on work function and doping of each interlayer, to bridge an work function difference as high as 1.6 eV. We also find solutions that minimize the doping required of the interlayers in order to minimize optical absorption due to free carriers in the graded recombination layer (GRL). We demonstrate a family of new GRL designs experimentally and highlight the benefits of the progression of dopings and work functions in the interlayers. © 2012 American Chemical Society.

Rationing with baselines

DEFF Research Database (Denmark)

Hougaard, Jens Leth; Moreno-Ternero, Juan D.; Østerdal, Lars Peter Raahave

2013-01-01

We introduce a new operator for general rationing problems in which, besides conflicting claims, individual baselines play an important role in the rationing process. The operator builds onto ideas of composition, which are not only frequent in rationing, but also in related problems...... such as bargaining, choice, and queuing. We characterize the operator and show how it preserves some standard axioms in the literature on rationing. We also relate it to recent contributions in such literature....

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

Science.gov (United States)

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

2015-10-01

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

Rational design of metal-organic electronic devices: A computational perspective

Science.gov (United States)

Chilukuri, Bhaskar

engineers to choose the appropriate metal electrodes considering the chemical interactions at the interface. Additionally, the calculations performed on the interfaces provided valuable insight into binding energies, charge redistribution, change in the energy levels, dipole formation, etc., which are important parameters to consider while fabricating an electronic device. The research described in this dissertation highlights the application of unique computational modeling methods at different levels of theory to guide the experimental chemists and device engineers toward a rational design of transition metal based electronic devices with low cost and high performance.

Rational design and optimization of downstream processes of virus particles for biopharmaceutical applications: current advances.

Science.gov (United States)

Vicente, Tiago; Mota, José P B; Peixoto, Cristina; Alves, Paula M; Carrondo, Manuel J T

2011-01-01

The advent of advanced therapies in the pharmaceutical industry has moved the spotlight into virus-like particles and viral vectors produced in cell culture holding great promise in a myriad of clinical targets, including cancer prophylaxis and treatment. Even though a couple of cases have reached the clinic, these products have yet to overcome a number of biological and technological challenges before broad utilization. Concerning the manufacturing processes, there is significant research focusing on the optimization of current cell culture systems and, more recently, on developing scalable downstream processes to generate material for pre-clinical and clinical trials. We review the current options for downstream processing of these complex biopharmaceuticals and underline current advances on knowledge-based toolboxes proposed for rational optimization of their processing. Rational tools developed to increase the yet scarce knowledge on the purification processes of complex biologicals are discussed as alternative to empirical, "black-boxed" based strategies classically used for process development. Innovative methodologies based on surface plasmon resonance, dynamic light scattering, scale-down high-throughput screening and mathematical modeling for supporting ion-exchange chromatography show great potential for a more efficient and cost-effective process design, optimization and equipment prototyping. Copyright © 2011 Elsevier Inc. All rights reserved.

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

Science.gov (United States)

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.

Personal Autonomy and Rational Suicide.

Science.gov (United States)

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…

Inaugurating Rationalization: Three Field Studies Find Increased Rationalization When Anticipated Realities Become Current.

Science.gov (United States)

Laurin, Kristin

2018-04-01

People will often rationalize the status quo, reconstruing it in an exaggeratedly positive light. They will even rationalize the status quo they anticipate, emphasizing the upsides and minimizing the downsides of sociopolitical realities they expect to take effect. Drawing on recent findings on the psychological triggers of rationalization, I present results from three field studies, one of which was preregistered, testing the hypothesis that an anticipated reality becoming current triggers an observable boost in people's rationalizations. San Franciscans rationalized a ban on plastic water bottles, Ontarians rationalized a targeted smoking ban, and Americans rationalized the presidency of Donald Trump, more in the days immediately after these realities became current compared with the days immediately before. Additional findings show evidence for a mechanism underlying these behaviors and rule out alternative accounts. These findings carry implications for scholarship on rationalization, for understanding protest behavior, and for policymakers.

Realization theory for rational systems: Minimal rational realizations

NARCIS (Netherlands)

J. Nemcová (Jana); J.H. van Schuppen (Jan)

2010-01-01

htmlabstractThe study of realizations of response maps is a topic of control and system theory. Realization theory is used in system identification and control synthesis. A minimal rational realization of a given response map p is a rational realization of p such that the dimension of its state

The Boundedly Rational User Equilibrium : A parametric analysis with application to the Network Design Problem

NARCIS (Netherlands)

Eikenbroek, Oskar Adriaan Louis; Still, Georg J.; van Berkum, E.C.; Kern, Walter

In this paper, we study a static traffic assignment that accounts for the boundedly rational route choice behavior of travelers. This assignment induces uncertainties to the ex-ante evaluation of a policy measure: the boundedly rational assignment is non-unique and the indifference band is an

METHODS FOR RECOMBINANT EXPRESSION AND FUNCTIONAL CHARACTERIZATION OF HUMAN CANNABINOID RECEPTOR CB2

Directory of Open Access Journals (Sweden)

Alexei A. Yeliseev

2013-03-01

Full Text Available Cannabinoid receptor CB2 is a seven transmembrane-domain integral membrane protein that belongs to a large superfamily of G protein-coupled receptors (GPCR. CB2 is a part of the endocannabinoid system that plays vital role in regulation of immune response, inflammation, pain sensitivity, obesity and other physiological responses. Information about the structure and mechanisms of functioning of this receptor in cell membranes is essential for the rational development of specific pharmaceuticals. Here we review the methodology for recombinant expression, purification, stabilization and biochemical characterization of CB2 suitable for preparation of multi-milligram quantities of functionally active receptor. The biotechnological protocols include expression of the recombinant CB2 in E. coli cells as a fusion with the maltose binding protein, stabilization with a high affinity ligand and a derivative of cholesterol in detergent micelles, efficient purification by tandem affinity chromatography, and reconstitution of the receptor into lipid bilayers. The purified recombinant CB2 receptor is amenable to functional and structural studies including nuclear magnetic resonance spectroscopy and a wide range of biochemical and biophysical techniques.

Elaborating and Making Rational Decisions in Designing Process Operations of a Group of Holes

Directory of Open Access Journals (Sweden)

A. I. Solov'ev

2015-01-01

Full Text Available To manufacture engineering products are used expensive multi-purpose CNC machines with five operated coordinates, allowing a single setup of the work-piece to process a group of holes in the housing part from all sides.Because of the haphazard arrangement of a large number of holes available in the space it is difficult to ensure the effective use of these machines.Onsite operational research, conducted on six CNC GS-500 models, involved actual observations and time measurements during 15 working shifts, processing of observation results, and calculations of equipment performance parameters such as machine utilization rate, arrangement and changeover time loss, and real output. Time loss (downtime because of arrangement amounted 44.52%, while that of due to changeover was 20.1% of the total downtime value. These downtimes hide irrational design solutions concerning the engineering process and a large number of changeovers for a new operation to process a group of the specified work-pieces.It is found that to reduce the changeover downtimes it is necessary to increase, first of all, the average number of single tool travels per one setup in generalized characteristics of a group of the work-pieces. That means to increase a changeover concentration of processing within a single operation, as well as to choose rational values for machining a batch of the work-pieces. Under study conditions, it is, at least. 20-50 pieces.To implement a development of the principle of increasing concentration of the processing changeovers it is advised to apply the developed mathematical models, algorithms, and programs that can be used, as modules or their parts, in computer-aided design (CAD systems. This allows a 3-5 times reduction in time to find the rational option of the work-piece position on the machine work surface when developing a process technology, a review and an analysis of more than the usual number of such possible options. It also improves the

The Effect of Soy Sauce Waste in Ration on Performance of Mojosari Duck

Directory of Open Access Journals (Sweden)

G. A. A. Larasati

2017-06-01

Full Text Available The purpose of study was to determined the effect of soy sauce waste in ration in the ration on the performance of Mojosari duck. The materials used were 240 of Mojosari which are 20 weeks olds with average body weight 1,385.0 ± 130.85 grams (CV = 9.44%. Feed ingredients used were, rice bran, soybean meal, yellow corn, fish meal, pollard and premix. The design that used was Completely Randomized Design (CRD with 4 treatments and 6 replications.The treatment applied soy sauce waste at level 5, 7,5 and 10%. The parameters observed were consumption, egg production, feed conversion. The data were analyzed by analysis of variance with F test. The results showed that soy sauce waste did not effected on performance (consumption of ration, egg production, ration conversion of Mojosari duck. The conclusion of this research is soy sauce waste be used as feed stuff of Mojosari duck ration until level 10%.

Many faces of rationality: Implications of the great rationality debate for clinical decision‐making

Science.gov (United States)

Elqayam, Shira

2017-01-01

Abstract Given that more than 30% of healthcare costs are wasted on inappropriate care, suboptimal care is increasingly connected to the quality of medical decisions. It has been argued that personal decisions are the leading cause of death, and 80% of healthcare expenditures result from physicians' decisions. Therefore, improving healthcare necessitates improving medical decisions, ie, making decisions (more) rational. Drawing on writings from The Great Rationality Debate from the fields of philosophy, economics, and psychology, we identify core ingredients of rationality commonly encountered across various theoretical models. Rationality is typically classified under umbrella of normative (addressing the question how people “should” or “ought to” make their decisions) and descriptive theories of decision‐making (which portray how people actually make their decisions). Normative theories of rational thought of relevance to medicine include epistemic theories that direct practice of evidence‐based medicine and expected utility theory, which provides the basis for widely used clinical decision analyses. Descriptive theories of rationality of direct relevance to medical decision‐making include bounded rationality, argumentative theory of reasoning, adaptive rationality, dual processing model of rationality, regret‐based rationality, pragmatic/substantive rationality, and meta‐rationality. For the first time, we provide a review of wide range of theories and models of rationality. We showed that what is “rational” behaviour under one rationality theory may be irrational under the other theory. We also showed that context is of paramount importance to rationality and that no one model of rationality can possibly fit all contexts. We suggest that in context‐poor situations, such as policy decision‐making, normative theories based on expected utility informed by best research evidence may provide the optimal approach to medical decision�

Rational design, synthesis, and pharmacological evaluation of 2-azanorbornane-3-exo,5-endo-dicarboxylic acid

DEFF Research Database (Denmark)

Bunch, Lennart; Liljefors, Tommy; Greenwood, Jeremy R

2003-01-01

conformationally restricted (S)-glutamic acid (Glu) analogue intended as a mimic of the folded Glu conformation. The synthesis of 1 was completed in its racemic form in eight steps from commercially available starting materials. As a key step, the first facially selective hydroboration of a 5-methylidene[2......The design and synthesis of conformationally restricted analogues of alpha-amino acids is an often used strategy in medicinal chemistry research. Here we present the rational design, synthesis, and pharmacological evaluation of 2-azanorbornane-3-exo,5-endo-dicarboxylic acid (1), a novel...... studies on native 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) (IC(50) > 300 microM, [(3)H]AMPA) or kainic acid (IC(50) > 160 microM, [(3)H]kainic acid) receptors nor in binding studies on the cloned iGluR5,6 subtypes (IC(50) > 300 microM, [(3)H]kainic acid)....

Rational design of single-molecule magnets: a supramolecular approach.

Science.gov (United States)

Glaser, Thorsten

2011-01-07

Since the discovery that Mn(12)OAc acts as a single-molecule magnet (SMM), an increasing number of transition metal complexes have been demonstrated to behave as SMMs. The signature of a SMM is a slow relaxation of the magnetization at low temperatures accompanied by a magnetic hysteresis. The origin of SMM behaviour is the existence of an appreciable thermal barrier U for spin-reversal called magnetic anisotropy barrier which is related to the combination of a large total spin ground state (S(t)) and an easy-axis magnetic anisotropy. The extensive research on Mn(12)OAc and other SMMs has established more prerequisites for a rational development of new SMMs besides the high-spin ground state and the magnetic anisotropy: the symmetry should be at least C(3) to minimize the quantum tunneling of the magnetization through the anisotropy barrier but lower than cubic to avoid the cancellation of the local anisotropies upon projection onto the spin ground state. Based on these prerequisites, we have designed the ligand triplesalen which combines the phloroglucinol bridging unit for high spin ground states by the spin-polarization mechanism with a salen-like ligand environment for single-site magnetic anisotropies by a strong tetragonal ligand field. The C(3) symmetric, trinuclear complexes of the triplesalen ligand (talen(t-Bu(2)))(6-) exhibit a strong ligand folding resulting in an overall bowl-shaped molecular structure. This ligand folding preorganizes the axial coordination sites of the metal salen subunits for the complementary binding of three facial nitrogen atoms of a hexacyanometallate unit. This leads to a high driving force for the formation of heptanuclear complexes [M(t)(6)M(c)](n+) by the assembly of three molecular building blocks. Attractive van der Waals interactions of the tert-butyl phenyl units of two triplesalen trinuclear building blocks increase the driving force. In this respect, we have been able to synthesize the isostructural series [Mn(III)(6

Many faces of rationality: Implications of the great rationality debate for clinical decision-making.

Science.gov (United States)

Djulbegovic, Benjamin; Elqayam, Shira

2017-10-01

Given that more than 30% of healthcare costs are wasted on inappropriate care, suboptimal care is increasingly connected to the quality of medical decisions. It has been argued that personal decisions are the leading cause of death, and 80% of healthcare expenditures result from physicians' decisions. Therefore, improving healthcare necessitates improving medical decisions, ie, making decisions (more) rational. Drawing on writings from The Great Rationality Debate from the fields of philosophy, economics, and psychology, we identify core ingredients of rationality commonly encountered across various theoretical models. Rationality is typically classified under umbrella of normative (addressing the question how people "should" or "ought to" make their decisions) and descriptive theories of decision-making (which portray how people actually make their decisions). Normative theories of rational thought of relevance to medicine include epistemic theories that direct practice of evidence-based medicine and expected utility theory, which provides the basis for widely used clinical decision analyses. Descriptive theories of rationality of direct relevance to medical decision-making include bounded rationality, argumentative theory of reasoning, adaptive rationality, dual processing model of rationality, regret-based rationality, pragmatic/substantive rationality, and meta-rationality. For the first time, we provide a review of wide range of theories and models of rationality. We showed that what is "rational" behaviour under one rationality theory may be irrational under the other theory. We also showed that context is of paramount importance to rationality and that no one model of rationality can possibly fit all contexts. We suggest that in context-poor situations, such as policy decision-making, normative theories based on expected utility informed by best research evidence may provide the optimal approach to medical decision-making, whereas in the context

Rationality and drug use: an experimental approach.

Science.gov (United States)

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.

Adolescent rationality.

Science.gov (United States)

Moshman, David

2013-01-01

Adolescents are commonly seen as irrational, a position supported to varying degrees by many developmentalists, who often appeal to recent research on adolescent brains. Careful review of relevant evidence, however, shows that (1) adults are less rational than is generally assumed, (2) adolescents (and adults) are categorically different from children with respect to the attainment of advanced levels of rationality and psychological functioning, and (3) adolescents and adults do not differ categorically from each other with respect to any rational competencies, irrational tendencies, brain structures, or neurological functioning. Development often continues in adolescence and beyond but categorical claims about adolescents as distinct from adults cannot be justified. A review of U.S. Supreme Court decisions concerning intellectual freedom, reproductive freedom, and criminal responsibility shows ongoing ambivalence and confusion about the rationality of adolescents. Developmental theory and research suggest that adolescents should be conceptualized as young adults, not immature brains, with important implications for their roles, rights, and responsibilities.

Love and rationality: on some possible rational effects of love

Directory of Open Access Journals (Sweden)

Gustavo Ortiz-Millán

Full Text Available In this paper I defend the idea that rather than disrupting rationality, as the common-sense conception has done it, love may actually help us to develop rational ways of thinking and acting. I make the case for romantic or erotic love, since this is the kind of love that is more frequently associated with irrationality in acting and thinking. I argue that this kind of love may make us develop epistemic and practical forms of rationality. Based on an analysis of its characteristic action tendencies, I argue that love may help us to develop an instrumental form of rationality in determining the best means to achieve the object of love. It may also narrow down the number of practical considerations that may help us to achieve our goals. Finally, love may generate rational ways of belief-formation by framing the parameters taken into account in perception and attention, and by bringing into light only a small portion of the epistemic information available. Love may make us perceive reality more acutely.

CONTRIBUTIONS TO RATIONAL APPROXIMATION,

Science.gov (United States)

Some of the key results of linear Chebyshev approximation theory are extended to generalized rational functions. Prominent among these is Haar’s...linear theorem which yields necessary and sufficient conditions for uniqueness. Some new results in the classic field of rational function Chebyshev...Furthermore a Weierstrass type theorem is proven for rational Chebyshev approximation. A characterization theorem for rational trigonometric Chebyshev approximation in terms of sign alternation is developed. (Author)

Rational points, rational curves, and entire holomorphic curves on projective varieties

CERN Document Server

Gasbarri, Carlo; Roth, Mike; Tschinkel, Yuri

2015-01-01

This volume contains papers from the Short Thematic Program on Rational Points, Rational Curves, and Entire Holomorphic Curves and Algebraic Varieties, held from June 3-28, 2013, at the Centre de Recherches Mathématiques, Université de Montréal, Québec, Canada. The program was dedicated to the study of subtle interconnections between geometric and arithmetic properties of higher-dimensional algebraic varieties. The main areas of the program were, among others, proving density of rational points in Zariski or analytic topology on special varieties, understanding global geometric properties of rationally connected varieties, as well as connections between geometry and algebraic dynamics exploring new geometric techniques in Diophantine approximation.

Recombinant Programming

OpenAIRE

Pawlak , Renaud; Cuesta , Carlos; Younessi , Houman

2004-01-01

This research report presents a promising new approach to computation called Recombinant Programming. The novelty of our approach is that it separates the program into two layers of computation: the recombination and the interpretation layer. The recombination layer takes sequences as inputs and allows the programmer to recombine these sequences through the definition of cohesive code units called extensions. The output of such recombination is a mesh that can be used by the interpretation la...

Application of 3D-QSAR in the rational design of receptor ligands and enzyme inhibitors.

Science.gov (United States)

Mor, Marco; Rivara, Silvia; Lodola, Alessio; Lorenzi, Simone; Bordi, Fabrizio; Plazzi, Pier Vincenzo; Spadoni, Gilberto; Bedini, Annalida; Duranti, Andrea; Tontini, Andrea; Tarzia, Giorgio

2005-11-01

Quantitative structure-activity relationships (QSARs) are frequently employed in medicinal chemistry projects, both to rationalize structure-activity relationships (SAR) for known series of compounds and to help in the design of innovative structures endowed with desired pharmacological actions. As a difference from the so-called structure-based drug design tools, they do not require the knowledge of the biological target structure, but are based on the comparison of drug structural features, thus being defined ligand-based drug design tools. In the 3D-QSAR approach, structural descriptors are calculated from molecular models of the ligands, as interaction fields within a three-dimensional (3D) lattice of points surrounding the ligand structure. These descriptors are collected in a large X matrix, which is submitted to multivariate analysis to look for correlations with biological activity. Like for other QSARs, the reliability and usefulness of the correlation models depends on the validity of the assumptions and on the quality of the data. A careful selection of compounds and pharmacological data can improve the application of 3D-QSAR analysis in drug design. Some examples of the application of CoMFA and CoMSIA approaches to the SAR study and design of receptor or enzyme ligands is described, pointing the attention to the fields of melatonin receptor ligands and FAAH inhibitors.

Recombiner

International Nuclear Information System (INIS)

Kikuchi, Nobuo.

1983-01-01

Purpose: To shorten the pre-heating time for a recombiner and obtain a uniform temperature distribution for the charged catalyst layer in a BWR type reactor. Constitution: A pre-heating heater is disposed to the outer periphery of a vessel for a recombiner packed with catalysts for recombining hydrogen and oxygen in gases flowing through a radioactive gaseous wastes processing system. Heat pipes for transmitting the heat applied to said container to the catalyst are disposed vertically and horizontally within the container. Different length of the heat pipes are combined. In this way, pre-heating time for the recombiner before the operation start and before the system switching can be shortened and the uniform pre-heating for the inside of the recombiner is also made possible. Further, heater control in the pre-heating can be carried out effectively and with ease. (Moriyama, K.)

Irrational Rationality of Terrorism

Directory of Open Access Journals (Sweden)

Robert Nalbandov

2013-12-01

Full Text Available The present article deals with the ontological problem of applying the rational choice frameworks to the study of terrorism. It testing the application of the rational choice to the “old” (before the end of the Cold War and the “new” (after the end of the Cold War terrorisms. It starts with analyzing the fundamentals of rationality and applies it at two levels: the individual (actors and group (collective via two outlooks: tactical (short-term and strategic (long-term. The main argument of the article is that while the “old” terrorism can be explained by the rational choice theory its “new” version represents a substantial departure from rationality.

Appendix to rationally designing of machine tools for example of universal lathe

Directory of Open Access Journals (Sweden)

Pejović Branko B.

2015-01-01

Full Text Available In this paper, for the universal machine tool for turning and function of the thrust of the cutting speed for blasting area efficiency and stability of the tool and sectional filings. These dependencies were used to determine the main characteristics of the optimal and maximum operating power equipment. Based on this, an analysis of the increase in operating power equipment typical cases in order to adapt to the new needs of exploitation properties and improve productivity. Using the previous analysis, it was determined the best solution in terms of the rational design of machines, by ensuring the simultaneous use of the main features on the basis of increase in speed with the use of tools and higher stability. In order to better display problems, an analysis of the appropriate diagrams P-V and V-D. On a typical example of the manufacturing practice at the end of the work, we demonstrate improvement of exploitation characteristics of a universal machine through appropriate calculations in terms of new needs adjustment feature, where it is expected that the reconstruction of the smallest machines.

Lying for Strategic Advantage: Rational and Boundedly Rational Misrepresentation of Intentions

OpenAIRE

Crawford, Vincent P.

2001-01-01

Starting from Hendricks and McAfee's (2000) example of the Allies' decision to feint at Calais and attack at Normandy on D-Day, this paper models misrepresentation of intentions to competitors or enemies. Allowing for the possibility of bounded strategic rationality and rational players' responses to it yields a sensible account of lying via costless, noiseless messages. In many cases the model has generically unique pure-strategy sequential equilibria, in which rational players exploit bound...

Determinants of Actor Rationality

DEFF Research Database (Denmark)

Ellegaard, Chris

Industrial companies must exercise influence on their suppliers (or supplier actors). Actor rationality is a central theme connected to this management task. In this article, relevant literature is studied with the purpose of shedding light on determinants of actor rationality. Two buyer-supplier...... relations are investigated in a multiple case study, leading to the proposal of various additional factors that determine and shape actor rationality. Moreover a conceptual model of rationality determinants in the buyer-supplier relation is proposed, a model that may help supply managers analyse...

Two Concepts of Rationality

Directory of Open Access Journals (Sweden)

Danny Frederick

2010-02-01

Full Text Available The dominant tradition in Western philosophy sees rationality as dictating. Thus rationality may require that we believe the best explanation and simple conceptual truths and that we infer in accordance with evident rules of inference. I argue that, given what we know about the growth of knowledge, this authoritarian concept of rationality leads to absurdities and should be abandoned. I then outline a libertarian concept of rationality, derived from Popper, which eschews the dictates and which sees a rational agent as one who questions, criticises, conjectures and experiments. I argue that, while the libertarian approach escapes the absurdities of the authoritarian, it requires two significant developments and an important clarification to be made fully consistent with itself.

Containment air circulation for optimal hydrogen recombination

International Nuclear Information System (INIS)

Spinks, N.; Krause, M.

1997-01-01

An accepted first-line defense for hydrogen mitigation is to design for the hydrogen to be rapidly mixed with the containment atmosphere and diluted to below flammability concentrations. Then, as hydrogen continues to be produced in the longer term, recombiners can be used to remove hydrogen: recombiners can be located in forced-air ducts or passive recombiners can be distributed within containment and the heat of recombination used to promote local air circulation. However, this principle does not eliminate the possibility of high hydrogen concentrations at locations removed from the recombiners. An improvement on this strategy is to arrange for a specific, buoyancy-driven, overall circulation of the containment atmosphere such that the recombiners can be located within the recirculation flow, immediately downstream of the hydrogen source. This would make the mixing process more predictable and solve the mass-transfer problem associated with distributed recombiners. Ideally, the recombiners would be located just above the hydrogen source so that the heat of recombination would assist the overall circulation. In this way, the hydrogen would be removed as close as possible to the source, thereby minimizing the amount of hydrogen immediately downstream of the source and reducing the hydrogen concentration to acceptable levels at other locations. Such a strategy requires the containment volume to be divided into an upflow path, past the hydrogen source and the recombiner, and a downflow path to complete the circuit. The flow could be generated actively using fans or passively using buoyancy forces arising from the difference in density of gases in the upfiow and downflow paths; the gases in the downflow path being cooled at an elevated heat sink. (author)

Rationality and institutions : an inquiry into the normative implications of rational choice theory

OpenAIRE

Engelen, Bart

2007-01-01

I aim to analyze in this dissertation what a desirable basic institutional structure looks like from the perspective of rationality. While the main topic is thus normative in nature, I start by clarifying in the first part what the notion of rationality exactly entails. I do so by focusing explicitly on the economic conception of rationality, according to which a rational individual is motivated to serve his self-interest on the basis of cost-benefit calculations. Such a Homo Economicus is ch...

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

Science.gov (United States)

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,…

Comparative immunological evaluation of recombinant Salmonella Typhimurium strains expressing model antigens as live oral vaccines.

Science.gov (United States)

Zheng, Song-yue; Yu, Bin; Zhang, Ke; Chen, Min; Hua, Yan-Hong; Yuan, Shuofeng; Watt, Rory M; Zheng, Bo-Jian; Yuen, Kwok-Yung; Huang, Jian-Dong

2012-09-26

Despite the development of various systems to generate live recombinant Salmonella Typhimurium vaccine strains, little work has been performed to systematically evaluate and compare their relative immunogenicity. Such information would provide invaluable guidance for the future rational design of live recombinant Salmonella oral vaccines. To compare vaccine strains encoded with different antigen delivery and expression strategies, a series of recombinant Salmonella Typhimurium strains were constructed that expressed either the enhanced green fluorescent protein (EGFP) or a fragment of the hemagglutinin (HA) protein from the H5N1 influenza virus, as model antigens. The antigens were expressed from the chromosome, from high or low-copy plasmids, or encoded on a eukaryotic expression plasmid. Antigens were targeted for expression in either the cytoplasm or the outer membrane. Combinations of strategies were employed to evaluate the efficacy of combined delivery/expression approaches. After investigating in vitro and in vivo antigen expression, growth and infection abilities; the immunogenicity of the constructed recombinant Salmonella strains was evaluated in mice. Using the soluble model antigen EGFP, our results indicated that vaccine strains with high and stable antigen expression exhibited high B cell responses, whilst eukaryotic expression or colonization with good construct stability was critical for T cell responses. For the insoluble model antigen HA, an outer membrane expression strategy induced better B cell and T cell responses than a cytoplasmic strategy. Most notably, the combination of two different expression strategies did not increase the immune response elicited. Through systematically evaluating and comparing the immunogenicity of the constructed recombinant Salmonella strains in mice, we identified their respective advantages and deleterious or synergistic effects. Different construction strategies were optimally-required for soluble versus

Rationing medical education.

African Journals Online (AJOL)

This paper discussed the pros and cons of the application of rationing to medical education and the different ... Different types of rationing exist in healthcare professional education. ... state-of-the-art resources, technology and tutors con-.

Rationality problem for algebraic tori

CERN Document Server

Hoshi, Akinari

2017-01-01

The authors give the complete stably rational classification of algebraic tori of dimensions 4 and 5 over a field k. In particular, the stably rational classification of norm one tori whose Chevalley modules are of rank 4 and 5 is given. The authors show that there exist exactly 487 (resp. 7, resp. 216) stably rational (resp. not stably but retract rational, resp. not retract rational) algebraic tori of dimension 4, and there exist exactly 3051 (resp. 25, resp. 3003) stably rational (resp. not stably but retract rational, resp. not retract rational) algebraic tori of dimension 5. The authors make a procedure to compute a flabby resolution of a G-lattice effectively by using the computer algebra system GAP. Some algorithms may determine whether the flabby class of a G-lattice is invertible (resp. zero) or not. Using the algorithms, the suthors determine all the flabby and coflabby G-lattices of rank up to 6 and verify that they are stably permutation. The authors also show that the Krull-Schmidt theorem for G-...

Rational Approximations to Rational Models: Alternative Algorithms for Category Learning

Science.gov (United States)

Sanborn, Adam N.; Griffiths, Thomas L.; Navarro, Daniel J.

2010-01-01

Rational models of cognition typically consider the abstract computational problems posed by the environment, assuming that people are capable of optimally solving those problems. This differs from more traditional formal models of cognition, which focus on the psychological processes responsible for behavior. A basic challenge for rational models…

Adsorption of rationally designed "surf-tides" to a liquid-crystal interface.

Science.gov (United States)

Badami, Joseph V; Bernstein, Chaim; Maldarelli, Charles; Tu, Raymond S

2015-09-07

The interfacial adsorption of proteins in surfactant laden systems occurs both in nature and industrial processing, yet much of the fundamental behavior behind these systems is still not well understood. We report the development of a system that monitors optical transitions of a liquid-crystalline/aqueous interface to examine the dynamics of adsorption of two rationally designed model peptide molecules. The two molecules synthesized in this study were both designed to become surface-active upon folding and contain the same net charge of +3, but one of the peptides, K-2.5, has its three charges separated by 2.5 amino acids as compared to K-6.0, which has its three charges separated by 6 amino acids. Our study examines the roles that surfactant adsorption, peptide charge distribution and secondary structure have on the relative adsorption dynamics of these two models peptides onto a fluid/fluid interface. Using the optical detection of molecular adsorption and image analysis of these events, we obtain quantitative information about the dynamics as a function of the charge spacing and initial peptide concentration. We show that both peptides initially follow a diffusion-limited adsorption model onto the interface. Additionally, our results suggest that the K-6.0 peptides demonstrate enhanced adsorption kinetics, where the enhanced rates are a consequence of the well-folded adsorbed state and spatial distribution on the surface. These findings provide further insights into the role that charge spacing has on secondary structure and subsequently the dynamics of adsorption, while developing a versatile system capable of extracting quantitative information from a simple inexpensive optical system.

METHODOLOGICAL ASPECTS OF RATIONAL DESIGN FORMATION OF INFRASTRUCTURE OF AGRARIAN SECTOR OF UKRAINE

Directory of Open Access Journals (Sweden)

Ivan Korchynskyy

2016-11-01

Full Text Available Methodological aspects of formation of rational design of infrastructure of agrarian sector of Ukraine on the basis of the institutional approach and laws of architectonics are examined. It is shown that the agrarian sector of Ukraine is a complex socio-economic system, the formation and development of which is in the process of market transformation what is caused by institutional influences. In general the process of relations institutionalization imply their formalization and standardization, in other case the subject of public life could not predict the actions of other entities associated with him and ensure their cooperation. One of the specific characteristic of human society is formed institutional system that regulates behaviour. In the article the factors of influence on the conduct of being in charge subjects are considered in the conditions of development of market economy. The special attention is spared the institutional factors of the economy growing. Methodology. The meaning of “agricultural field” and “infrastructure” and their mutual consistency is classified. As the scientific method, the institutional approach of principles of architectonics has been used, which allowed to justify the creation of a rational approach to the design of infrastructure in agrarian sector as a whole on the basis, relation and interdependence of its elements, based on the fundamental laws of architectonics (law of equilibrium, law of the golden mean structuring. The article demonstrates a necessary of the choice of a theory of institutionalism as the main methodological basis for the study of the process of innovation development of economic system of Ukraine. It is determined that the inefficient activities of institutions in Ukraine are the main cause of the low level of innovation, which has a negative impact on the development of the economy as a whole. Results. Research points on new aspects of infrastructure as a part of the entire

Rational design of protamine nanocapsules as antigen delivery carriers.

Science.gov (United States)

González-Aramundiz, José Vicente; Presas, Elena; Dalmau-Mena, Inmaculada; Martínez-Pulgarín, Susana; Alonso, Covadonga; Escribano, José M; Alonso, María J; Csaba, Noemi Stefánia

2017-01-10

Current challenges in global immunization indicate the demand for new delivery strategies, which could be applied to the development of new vaccines against emerging diseases, as well as to improve safety and efficacy of currently existing vaccine formulations. Here, we report a novel antigen nanocarrier consisting of an oily core and a protamine shell, further stabilized with pegylated surfactants. These nanocarriers, named protamine nanocapsules, were rationally designed to promote the intracellular delivery of antigens to immunocompetent cells and to trigger an efficient and long-lasting immune response. Protamine nanocapsules have nanometric size, positive zeta potential and high association capacity for H1N1 influenza hemagglutinin, a protein that was used here as a model antigen. The new formulation shows an attractive stability profile both, as an aqueous suspension or a freeze-dried powder formulation. In vitro studies showed that protamine nanocapsules were efficiently internalized by macrophages without eliciting significant toxicity. In vivo studies indicate that antigen-loaded nanocapsules trigger immune responses comparable to those achieved with alum, even when using significantly lower antigen doses, thus indicating their adjuvant properties. These promising in vivo data, alongside with their versatility for the loading of different antigens and oily immunomodulators and their excellent stability profile, make these nanocapsules a promising platform for the delivery of antigens. Protamine sulphate (PubChem SID: 7849283), Sodium Cholate (PubChem CID: 23668194), Miglyol (PubChem CID: 53471835), α tocopherol (PubChem CID: 14985), Tween® 20(PubChem CID: 443314), Tween® 80(PubChem CID: 5281955), TPGS (PubChem CID: 71406). Copyright © 2016 Elsevier B.V. All rights reserved.

Rationally Designed TLR4 Ligands for Vaccine Adjuvant Discovery

Directory of Open Access Journals (Sweden)

Kelsey A. Gregg

2017-05-01

Full Text Available Adjuvant properties of bacterial cell wall components like MPLA (monophosphoryl lipid A are well described and have gained FDA approval for use in vaccines such as Cervarix. MPLA is the product of chemically modified lipooligosaccharide (LOS, altered to diminish toxic proinflammatory effects while retaining adequate immunogenicity. Despite the virtually unlimited number of potential sources among bacterial strains, the number of useable compounds within this promising class of adjuvants are few. We have developed bacterial enzymatic combinatorial chemistry (BECC as a method to generate rationally designed, functionally diverse lipid A. BECC removes endogenous or introduces exogenous lipid A-modifying enzymes to bacteria, effectively reprogramming the lipid A biosynthetic pathway. In this study, BECC is applied within an avirulent strain of Yersinia pestis to develop structurally distinct LOS molecules that elicit differential Toll-like receptor 4 (TLR4 activation. Using reporter cell lines that measure NF-κB activation, BECC-derived molecules were screened for the ability to induce a lower proinflammatory response than Escherichia coli LOS. Their structures exhibit varied, dose-dependent, TLR4-driven NF-κB activation with both human and mouse TLR4 complexes. Additional cytokine secretion screening identified molecules that induce levels of tumor necrosis factor alpha (TNF-α and interleukin-8 (IL-8 comparable to the levels induced by phosphorylated hexa-acyl disaccharide (PHAD. The lead candidates demonstrated potent immunostimulation in mouse splenocytes, human primary blood mononuclear cells (PBMCs, and human monocyte-derived dendritic cells (DCs. This newly described system allows directed programming of lipid A synthesis and has the potential to generate a diverse array of TLR4 agonist candidates.

Photoionization and Recombination

Science.gov (United States)

Nahar, Sultana N.

2000-01-01

Theoretically self-consistent calculations for photoionization and (e + ion) recombination are described. The same eigenfunction expansion for the ion is employed in coupled channel calculations for both processes, thus ensuring consistency between cross sections and rates. The theoretical treatment of (e + ion) recombination subsumes both the non-resonant recombination ("radiative recombination"), and the resonant recombination ("di-electronic recombination") processes in a unified scheme. In addition to the total, unified recombination rates, level-specific recombination rates and photoionization cross sections are obtained for a large number of atomic levels. Both relativistic Breit-Pauli, and non-relativistic LS coupling, calculations are carried out in the close coupling approximation using the R-matrix method. Although the calculations are computationally intensive, they yield nearly all photoionization and recombination parameters needed for astrophysical photoionization models with higher precision than hitherto possible, estimated at about 10-20% from comparison with experimentally available data (including experimentally derived DR rates). Results are electronically available for over 40 atoms and ions. Photoionization and recombination of He-, and Li-like C and Fe are described for X-ray modeling. The unified method yields total and complete (e+ion) recombination rate coefficients, that can not otherwise be obtained theoretically or experimentally.

Catalytic hydrogen recombination for nuclear containments

International Nuclear Information System (INIS)

Koroll, G.W.; Lau, D.W.P.; Dewit, W.A.; Graham, W.R.C.

1994-01-01

Catalytic recombiners appear to be a credible option for hydrogen mitigation in nuclear containments. The passive operation, versatility and ease of back fitting are appealing for existing stations and new designs. Recently, a generation of wet-proofed catalyst materials have been developed at AECL which are highly specific to H 2 -O 2 , are active at ambient temperatures and are being evaluated for containment applications. Two types of catalytic recombiners were evaluated for hydrogen removal in containments based on the AECL catalyst. The first is a catalytic combustor for application in existing air streams such as provided by fans or ventilation systems. The second is an autocatalytic recombiner which uses the enthalpy of reaction to produce natural convective flow over the catalyst elements. Intermediate-scale results obtained in 6 m 3 and 10 m 3 spherical and cylindrical vessels are given to demonstrate self-starting limits, operating limits, removal capacity, scaling parameters, flow resistance, mixing behaviour in the vicinity of an operating recombiner and sensitivity to poisoning, fouling and radiation. (author). 13 refs., 10 figs

Optimal public rationing and price response.

Science.gov (United States)

Grassi, Simona; Ma, Ching-To Albert

2011-12-01

We study optimal public health care rationing and private sector price responses. Consumers differ in their wealth and illness severity (defined as treatment cost). Due to a limited budget, some consumers must be rationed. Rationed consumers may purchase from a monopolistic private market. We consider two information regimes. In the first, the public supplier rations consumers according to their wealth information (means testing). In equilibrium, the public supplier must ration both rich and poor consumers. Rationing some poor consumers implements price reduction in the private market. In the second information regime, the public supplier rations consumers according to consumers' wealth and cost information. In equilibrium, consumers are allocated the good if and only if their costs are below a threshold (cost effectiveness). Rationing based on cost results in higher equilibrium consumer surplus than rationing based on wealth. Copyright © 2011 Elsevier B.V. All rights reserved.

Exploring rationality in schizophrenia

DEFF Research Database (Denmark)

Revsbech, Rasmus; Mortensen, Erik Lykke; Owen, Gareth

2015-01-01

Background Empirical studies of rationality (syllogisms) in patients with schizophrenia have obtained different results. One study found that patients reason more logically if the syllogism is presented through an unusual content. Aims To explore syllogism-based rationality in schizophrenia. Meth...... differences became non-significant. Conclusions When taking intelligence and neuropsychological performance into account, patients with schizophrenia and controls perform similarly on syllogism tests of rationality.......Background Empirical studies of rationality (syllogisms) in patients with schizophrenia have obtained different results. One study found that patients reason more logically if the syllogism is presented through an unusual content. Aims To explore syllogism-based rationality in schizophrenia. Method...... Thirty-eight first-admitted patients with schizophrenia and 38 healthy controls solved 29 syllogisms that varied in presentation content (ordinary v. unusual) and validity (valid v. invalid). Statistical tests were made of unadjusted and adjusted group differences in models adjusting for intelligence...

Respect for rational autonomy.

Science.gov (United States)

Walker, Rebecca L

2009-12-01

The standard notion of autonomy in medical ethics does not require that autonomous choices not be irrational. The paper gives three examples of seemingly irrational patient choices and discusses how a rational autonomy analysis differs from the standard view. It then considers whether a switch to the rational autonomy view would lead to overriding more patient decisions but concludes that this should not be the case. Rather, a determination of whether individual patient decisions are autonomous is much less relevant than usually considered in determining whether health care providers must abide by these decisions. Furthermore, respect for rational autonomy entails strong positive requirements of respect for the autonomy of the person as a rational decision maker. The rationality view of autonomy is conceptually stronger than the standard view, allows for a more nuanced understanding of the practical moral calculus involved in respecting patient autonomy, and promotes positive respect for patient autonomy.

Embodying rationality

OpenAIRE

Mastrogiorgio, Antonio; Petracca, Enrico

2016-01-01

The current notions of bounded rationality in economics share distinctive features with Simon’s original notion, which still influences the theoretical and experimental research in the fields of choice, judgment, decision making, problem solving, and social cognition. All these notions of bounded rationality are in fact equally rooted in the information-processing approach to human cognition, expressing the view that reasoning is disembodied and that it can be reduced to the processing of abs...

Suicide: rationality and responsibility for life.

Science.gov (United States)

Ho, Angela Onkay

2014-03-01

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. 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. 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. 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.

Capital Requirements and Credit Rationing

OpenAIRE

Itai Agur

2010-01-01

This paper analyzes the trade-off between financial stability and credit rationing that arises when increasing capital requirements. It extends the Stiglitz-Weiss model of credit rationing to allow for bank default. Bank capital structure then matters for lending incentives. With default and rationing endogenous, optimal capital requirements can be analyzed. Introducing bank financiers, the paper also shows that uninsured funding raises the sensitivity of rationing to capital requirements. In...

Rationally designed, heterologous S. cerevisiae transcripts expose novel expression determinants

Science.gov (United States)

Ben-Yehezkel, Tuval; Atar, Shimshi; Zur, Hadas; Diament, Alon; Goz, Eli; Marx, Tzipy; Cohen, Rafael; Dana, Alexandra; Feldman, Anna; Shapiro, Ehud; Tuller, Tamir

2015-01-01

Deducing generic causal relations between RNA transcript features and protein expression profiles from endogenous gene expression data remains a major unsolved problem in biology. The analysis of gene expression from heterologous genes contributes significantly to solving this problem, but has been heavily biased toward the study of the effect of 5′ transcript regions and to prokaryotes. Here, we employ a synthetic biology driven approach that systematically differentiates the effect of different regions of the transcript on gene expression up to 240 nucleotides into the ORF. This enabled us to discover new causal effects between features in previously unexplored regions of transcripts, and gene expression in natural regimes. We rationally designed, constructed, and analyzed 383 gene variants of the viral HRSVgp04 gene ORF, with multiple synonymous mutations at key positions along the transcript in the eukaryote S. cerevisiae. Our results show that a few silent mutations at the 5′UTR can have a dramatic effect of up to 15 fold change on protein levels, and that even synonymous mutations in positions more than 120 nucleotides downstream from the ORF 5′end can modulate protein levels up to 160%–300%. We demonstrate that the correlation between protein levels and folding energy increases with the significance of the level of selection of the latter in endogenous genes, reinforcing the notion that selection for folding strength in different parts of the ORF is related to translation regulation. Our measured protein abundance correlates notably(correlation up to r = 0.62 (p=0.0013)) with mean relative codon decoding times, based on ribosomal densities (Ribo-Seq) in endogenous genes, supporting the conjecture that translation elongation and adaptation to the tRNA pool can modify protein levels in a causal/direct manner. This report provides an improved understanding of transcript evolution, design principles of gene expression regulation, and suggests simple

Development of novel recombinant biomimetic chimeric MPG-based peptide as nanocarriers for gene delivery: Imitation of a real cargo.

Science.gov (United States)

Majidi, Asia; Nikkhah, Maryam; Sadeghian, Faranak; Hosseinkhani, Saman

2016-10-01

In last decades great efforts have been devoted to the study of development of recombinant peptide based vectors that consist of biological motifs with potential applications in gene therapy. Recombinant Biomimetic Chimeric Vectors (rBCVs) are biopolymeric nanocarriers that are designed to mimic viral features to overcome the cellular obstacles in gene transferring pathway into cell nucleus. In this research, we designed and genetically engineered three novel rBCVs with similar sequences that differed in motifs arrangement and motif abundance: MPG-2H1, 2TMPG-2H1 and 2RMPG-2H1. The MPG as a famous amphipathic cell penetrating peptide is the main segment of these constructs which was studied for the first time in association with truncated histone H1 DNA condensing motif. Through the performance of several physicochemical and biological assays, the rBCVs were remarkably examined regarding transfection efficiency. The main objective of this study is focused on the importance of motif design in transfection efficiency of rBCVs on one hand, and the assessment of correlation between structural features and functionality of motifs on the other hand. The results revealed that all three kinds of rBCVs/pDNA nanoparticles with average sizes of 200nm could overwhelm the cellular obstacles associated with gene transfer, and lead to efficient gene delivery. Furthermore, no significant toxicity was perceived and efficient endosome disruptive activity was obtained. It is noteworthy to say among three mentioned constructs 2RMPG-2H1 showed the highest transfection efficiency. Overall the peptide based vectors hold great promise as a nontoxic and effective gene carrier in vitro and in vivo, besides the rational design possibility as the most vital advantages over the other non-viral gene delivery vectors. Copyright © 2016 Elsevier B.V. All rights reserved.

[Rationalization and rationing at the bedside. A normative and empirical status quo analysis].

Science.gov (United States)

Strech, D

2014-02-01

The topic of bedside rationing is increasingly discussed in Germany. Further need for clarification exists for the question how bedside rationing (e.g., in the area of overcare) can be justified despite coexistent inefficiencies. This paper outlines and analyses the relationship of waste avoidance and rationing from an ethical perspective. Empirical findings regarding the status quo of bedside rationing and rationalization are presented. These normative and empirical explorations will then be further specified regarding opportunities for future physician-driven activities to tackle overuse. The self-government partners in Germany should communicate more explicitly within their communities and to the public how and with which benchmarks they aim to reduce inefficient health care (overuse) in an appropriate manner. Physician-driven activities such as the "Choosing Wisely®" initiative in the USA could provide a first step to raise the awareness for overuse among physicians as well as in the public.

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

Science.gov (United States)

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

2018-02-27

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.

Simulation and Optimisation of CLIC's recombination complex

CERN Document Server

Costa, Raul; Barroso, Manuel

In this thesis we present the first Placet2 recombination simulations of the drive beam recombination complex (DBRC) design for the compact linear collider (CLIC). We start by presenting a review of the CLIC project and the DBRC’s role and design within it. We then discuss some of the core principles of beam dynamics and how tracking codes like Placet2 implement them. We follow that by presenting the design issues raised by our simulations and our proposed strategy to address them, key among which is a previously unknown parabolic dependency of the longitudinal position to the momentum (T 566 ), which threat- ens the efficiency of the power extraction structures. Through iterative opti- misation of the design, we eliminated this aberration both in the delay loop and in combiner ring 1. We also found the beam’s horizontal emittance to be significantly over the design budget (150 μm) and attempted to meet that budget, reaching 157 μm. In order to obtain this emittance value, an update to the combiner ring...

Rational BRDF.

Science.gov (United States)

Pacanowski, Romain; Salazar Celis, Oliver; Schlick, Christophe; Granier, Xavier; Poulin, Pierre; Cuyt, Annie

2012-11-01

Over the last two decades, much effort has been devoted to accurately measuring Bidirectional Reflectance Distribution Functions (BRDFs) of real-world materials and to use efficiently the resulting data for rendering. Because of their large size, it is difficult to use directly measured BRDFs for real-time applications, and fitting the most sophisticated analytical BRDF models is still a complex task. In this paper, we introduce Rational BRDF, a general-purpose and efficient representation for arbitrary BRDFs, based on Rational Functions (RFs). Using an adapted parametrization, we demonstrate how Rational BRDFs offer 1) a more compact and efficient representation using low-degree RFs, 2) an accurate fitting of measured materials with guaranteed control of the residual error, and 3) efficient importance sampling by applying the same fitting process to determine the inverse of the Cumulative Distribution Function (CDF) generated from the BRDF for use in Monte-Carlo rendering.

Surface Termination of M1 Phase and Rational Design of Propane Ammoxidation Catalysts

Energy Technology Data Exchange (ETDEWEB)

Guliants, Vadim [Univ. of Cincinnati, OH (United States)

2015-02-16

This final report describes major accomplishments in this research project which has demonstrated that the M1 phase is the only crystalline phase required for propane ammoxidation to acrylonitrile and that a surface monolayer terminating the ab planes of the M1 phase is responsible for their activity and selectivity in this reaction. Fundamental studies of the topmost surface chemistry and mechanism of propane ammoxidation over the Mo-V-(Te,Sb)-(Nb,Ta)-O M1 and M2 phases resulted in the development of quantitative understanding of the surface molecular structure – reactivity relationships for this unique catalytic system. These oxides possess unique catalytic properties among mixed metal oxides, because they selectively catalyze three alkane transformation reactions, namely propane ammoxidation to acrylonitrile, propane oxidation to acrylic acid and ethane oxidative dehydrogenation, all of considerable economic significance. Therefore, the larger goal of this research was to expand this catalysis to other alkanes of commercial interest, and more broadly, demonstrate successful approaches to rational design of improved catalysts that can be applied to other selective (amm)oxidation processes.

Is It Rational to Assume that Infants Imitate Rationally? A Theoretical Analysis and Critique

Science.gov (United States)

Paulus, Markus

2012-01-01

It has been suggested that preverbal infants evaluate the efficiency of others' actions (by applying a "principle of rational action") and that they imitate others' actions rationally. The present contribution presents a conceptual analysis of the claim that preverbal infants imitate rationally. It shows that this ability rests on at least three…

Adapting Rational Unified Process (RUP) approach in designing a secure e-Tendering model

Science.gov (United States)

Mohd, Haslina; Robie, Muhammad Afdhal Muhammad; Baharom, Fauziah; Darus, Norida Muhd; Saip, Mohamed Ali; Yasin, Azman

2016-08-01

e-Tendering is an electronic processing of the tender document via internet and allow tenderer to publish, communicate, access, receive and submit all tender related information and documentation via internet. This study aims to design the e-Tendering system using Rational Unified Process approach. RUP provides a disciplined approach on how to assign tasks and responsibilities within the software development process. RUP has four phases that can assist researchers to adjust the requirements of various projects with different scope, problem and the size of projects. RUP is characterized as a use case driven, architecture centered, iterative and incremental process model. However the scope of this study only focusing on Inception and Elaboration phases as step to develop the model and perform only three of nine workflows (business modeling, requirements, analysis and design). RUP has a strong focus on documents and the activities in the inception and elaboration phases mainly concern the creation of diagrams and writing of textual descriptions. The UML notation and the software program, Star UML are used to support the design of e-Tendering. The e-Tendering design based on the RUP approach can contribute to e-Tendering developers and researchers in e-Tendering domain. In addition, this study also shows that the RUP is one of the best system development methodology that can be used as one of the research methodology in Software Engineering domain related to secured design of any observed application. This methodology has been tested in various studies in certain domains, such as in Simulation-based Decision Support, Security Requirement Engineering, Business Modeling and Secure System Requirement, and so forth. As a conclusion, these studies showed that the RUP one of a good research methodology that can be adapted in any Software Engineering (SE) research domain that required a few artifacts to be generated such as use case modeling, misuse case modeling, activity

Frequent intra-subtype recombination among HIV-1 circulating in Tanzania.

Directory of Open Access Journals (Sweden)

Ireen E Kiwelu

Full Text Available The study estimated the prevalence of HIV-1 intra-subtype recombinant variants among female bar and hotel workers in Tanzania. While intra-subtype recombination occurs in HIV-1, it is generally underestimated. HIV-1 env gp120 V1-C5 quasispecies from 45 subjects were generated by single-genome amplification and sequencing (median (IQR of 38 (28-50 sequences per subject. Recombination analysis was performed using seven methods implemented within the recombination detection program version 3, RDP3. HIV-1 sequences were considered recombinant if recombination signals were detected by at least three methods with p-values of ≤0.05 after Bonferroni correction for multiple comparisons. HIV-1 in 38 (84% subjects showed evidence for intra-subtype recombination including 22 with HIV-1 subtype A1, 13 with HIV-1 subtype C, and 3 with HIV-1 subtype D. The distribution of intra-patient recombination breakpoints suggested ongoing recombination and showed selective enrichment of recombinant variants in 23 (60% subjects. The number of subjects with evidence of intra-subtype recombination increased from 29 (69% to 36 (82% over one year of follow-up, although the increase did not reach statistical significance. Adjustment for intra-subtype recombination is important for the analysis of multiplicity of HIV infection. This is the first report of high prevalence of intra-subtype recombination in the HIV/AIDS epidemic in Tanzania, a region where multiple HIV-1 subtypes co-circulate. HIV-1 intra-subtype recombination increases viral diversity and presents additional challenges for HIV-1 vaccine design.

Bounded Rationality and Budgeting

OpenAIRE

Ibrahim, Mukdad

2016-01-01

This article discusses the theory of bounded rationality which had been introduced by Herbert Simon in the 1950s. Simon introduced the notion of bounded rationality stating that while decision-makers strive for rationality, they are limited by the effect of the environment, their information process capacity and by the constraints on their information storage and retrieval capabilities. Moreover, this article tries to specifically blend this notion into budgeting, using the foundations of inc...

Biomimetics: From Bioinformatics to Rational Design of Dendrimers as Gene Carriers

Science.gov (United States)

Araya-Durán, Ingrid; Varas-Concha, Ignacio; Almonacid, Daniel Eduardo; González-Nilo, Fernando Danilo

2015-01-01

Biomimetics, or the use of principles of Nature for developing new materials, is a paradigm that could help Nanomedicine tremendously. One of the current challenges in Nanomedicine is the rational design of new efficient and safer gene carriers. Poly(amidoamine) (PAMAM) dendrimers are a well-known class of nanoparticles, extensively used as non-viral nucleic acid carriers, due to their positively charged end-groups. Yet, there are still several aspects that can be improved for their successful application in in vitro and in vivo systems, including their affinity for nucleic acids as well as lowering their cytotoxicity. In the search of new functional groups that could be used as new dendrimer-reactive groups, we followed a biomimetic approach to determine the amino acids with highest prevalence in protein-DNA interactions. Then we introduced them individually as terminal groups of dendrimers, generating a new class of nanoparticles. Molecular dynamics studies of two systems: PAMAM-Arg and PAMAM-Lys were also performed in order to describe the formation of complexes with DNA. Results confirmed that the introduction of amino acids as terminal groups in a dendrimer increases their affinity for DNA and the interactions in the complexes were characterized at atomic level. We end up by briefly discussing additional modifications that can be made to PAMAM dendrimers to turned them into promising new gene carriers. PMID:26382062

Rational valuations

Directory of Open Access Journals (Sweden)

Georg Spielthenner

2007-01-01

Full Text Available Valuations are ubiquitous. We may be for or against genetically modified food; we find some politicians irresponsible; we prefer Beethoven to rock ‘n’ roll or vice versa; some enjoy bird-watching while others find it boring; and we may think that we have to tighten up on green-house gas emissions. Valuing is pervasive and often we are not even aware that we are valuing. However, many of ourvaluations are ill grounded and rationally defective. They are frequently based on misinformation, sloppy thinking, prejudice, and are biased in many ways as psychological research shows. For this reason there is widespread agreement among phi-losophers that we need an account of substantive valuational rationality, both for the theory of practical reasoning and for ethics as well. My main objectin this paper is to outline such an account and to present a principle that allows a non-technical rational criticism of valuations

Rational emotions.

Science.gov (United States)

Meshulam, Meir; Winter, Eyal; Ben-Shakhar, Gershon; Aharon, Itzhak

2012-01-01

We present here the concept of rational emotions: Emotions may be directly controlled and utilized in a conscious, analytic fashion, enabling an individual to size up a situation, to determine that a certain "mental state" is strategically advantageous and adjust accordingly. Building on the growing body of literature recognizing the vital role of emotions in determining decisions, we explore the complementary role of rational choice in choosing emotional states. Participants played the role of "recipient" in the dictator game, in which an anonymous "dictator" decides how to split an amount of money between himself and the recipient. A subset of recipients was given a monetary incentive to be angry at low-split offers. That subset demonstrated increased physiological arousal at low offers relative to high offers as well as more anger than other participants. These results provide a fresh outlook on human decision-making and contribute to the continuing effort to build more complete models of rational behavior.

Models for Rational Number Bases

Science.gov (United States)

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)

Materials-by-design: computation, synthesis, and characterization from atoms to structures

Science.gov (United States)

Yeo, Jingjie; Jung, Gang Seob; Martín-Martínez, Francisco J.; Ling, Shengjie; Gu, Grace X.; Qin, Zhao; Buehler, Markus J.

2018-05-01

In the 50 years that succeeded Richard Feynman’s exposition of the idea that there is ‘plenty of room at the bottom’ for manipulating individual atoms for the synthesis and manufacturing processing of materials, the materials-by-design paradigm is being developed gradually through synergistic integration of experimental material synthesis and characterization with predictive computational modeling and optimization. This paper reviews how this paradigm creates the possibility to develop materials according to specific, rational designs from the molecular to the macroscopic scale. We discuss promising techniques in experimental small-scale material synthesis and large-scale fabrication methods to manipulate atomistic or macroscale structures, which can be designed by computational modeling. These include recombinant protein technology to produce peptides and proteins with tailored sequences encoded by recombinant DNA, self-assembly processes induced by conformational transition of proteins, additive manufacturing for designing complex structures, and qualitative and quantitative characterization of materials at different length scales. We describe important material characterization techniques using numerous methods of spectroscopy and microscopy. We detail numerous multi-scale computational modeling techniques that complements these experimental techniques: DFT at the atomistic scale; fully atomistic and coarse-grain molecular dynamics at the molecular to mesoscale; continuum modeling at the macroscale. Additionally, we present case studies that utilize experimental and computational approaches in an integrated manner to broaden our understanding of the properties of two-dimensional materials and materials based on silk and silk-elastin-like proteins.

Rational Design of Disulfide Bonds Increases Thermostability of a Mesophilic 1,3-1,4-β-Glucanase from Bacillus terquilensis.

Directory of Open Access Journals (Sweden)

Chengtuo Niu

Full Text Available 1,3-1,4-β-glucanase is an important biocatalyst in brewing industry and animal feed industry, while its low thermostability often reduces its application performance. In this study, the thermostability of a mesophilic β-glucanase from Bacillus terquilensis was enhanced by rational design and engineering of disulfide bonds in the protein structure. Protein spatial configuration was analyzed to pre-exclude the residues pairs which negatively conflicted with the protein structure and ensure the contact of catalytic center. The changes in protein overall and local flexibility among the wild-type enzyme and the designated mutants were predicted to select the potential disulfide bonds for enhancement of thermostability. Two residue pairs (N31C-T187C and P102C-N125C were chosen as engineering targets and both of them were proved to significantly enhance the protein thermostability. After combinational mutagenesis, the double mutant N31C-T187C/P102C-N125C showed a 48.3% increase in half-life value at 60°C and a 4.1°C rise in melting temperature (Tm compared to wild-type enzyme. The catalytic property of N31C-T187C/P102C-N125C mutant was similar to that of wild-type enzyme. Interestingly, the optimal pH of double mutant was shifted from pH6.5 to pH6.0, which could also increase its industrial application. By comparison with mutants with single-Cys substitutions, the introduction of disulfide bonds and the induced new hydrogen bonds were proved to result in both local and overall rigidification and should be responsible for the improved thermostability. Therefore, the introduction of disulfide bonds for thermostability improvement could be rationally and highly-effectively designed by combination with spatial configuration analysis and molecular dynamics simulation.

Rational design of modular circuits for gene transcription: A test of the bottom-up approach

Directory of Open Access Journals (Sweden)

Giordano Emanuele

2010-11-01

Full Text Available Abstract Background Most of synthetic circuits developed so far have been designed by an ad hoc approach, using a small number of components (i.e. LacI, TetR and a trial and error strategy. We are at the point where an increasing number of modular, inter-changeable and well-characterized components is needed to expand the construction of synthetic devices and to allow a rational approach to the design. Results We used interchangeable modular biological parts to create a set of novel synthetic devices for controlling gene transcription, and we developed a mathematical model of the modular circuits. Model parameters were identified by experimental measurements from a subset of modular combinations. The model revealed an unexpected feature of the lactose repressor system, i.e. a residual binding affinity for the operator site by induced lactose repressor molecules. Once this residual affinity was taken into account, the model properly reproduced the experimental data from the training set. The parameters identified in the training set allowed the prediction of the behavior of networks not included in the identification procedure. Conclusions This study provides new quantitative evidences that the use of independent and well-characterized biological parts and mathematical modeling, what is called a bottom-up approach to the construction of gene networks, can allow the design of new and different devices re-using the same modular parts.

Are security analysts rational? a literature review

OpenAIRE

Peixinho, Rúben; Coelho, Luís; Taffler, Richard J.

2005-01-01

Rational choice theory and bounded rationality constitute the basis for the discussion in several areas regarding human rationality. In finance, this discussion has been made between traditional finance and behavioural finance approach, which have different perspectives concerning market agents’ rationality. This paper reviews several studies addressing rationality among security analysts. The analysis shows that analysts’systematic optimism seems to be inconsistent with rationality....

Definition of culture conditions for Arxula adeninivorans, a rational basis for studying heterologous gene expression in this dimorphic yeast.

Science.gov (United States)

Stöckmann, Christoph; Palmen, Thomas G; Schroer, Kirsten; Kunze, Gotthard; Gellissen, Gerd; Büchs, Jochen

2014-06-01

The yeast Arxula adeninivorans is considered to be a promising producer of recombinant proteins. However, growth characteristics are poorly investigated and no industrial process has been established yet. Though of vital interest for strain screening and production processes, rationally defined culture conditions remain to be developed. A cultivation system was evolved based on targeted sampling and mathematical analysis of rationally designed small-scale cultivations in shake flasks. The oxygen and carbon dioxide transfer rates were analyzed as conclusive online parameters. Oxygen limitation extended cultivation and led to ethanol formation in cultures supplied with glucose. Cultures were inhibited at pH-values below 2.8. The phosphorus demand was determined as 1.55 g phosphorus per 100 g cell dry weight. Synthetic SYN6 medium with 20 g glucose l(-1) was optimized for cultivation in shake flasks by buffering at pH 6.4 with 140 mmol MES l(-1). Optimized SYN6 medium and operating conditions provided non-limited cultivations without by-product formation. A maximal specific growth rate of 0.32 h(-1) and short fermentations of 15 h were achieved. A pH optimum curve was derived from the oxygen transfer rates of differently buffered cultures, showing maximal growth between pH 2.8 and 6.5. Furthermore, it was shown that the applied medium and cultivation conditions were also suitable for non-limiting growth and product formation of a genetically modified A. adeninivorans strain expressing a heterologous phytase.

Recombiner

International Nuclear Information System (INIS)

Osumi, Morimichi.

1979-01-01

Purpose: To provide a recombiner which is capable of converting hydrogen gas into water by use of high-frequency heating at comparatively low temperatures and is safe and cheap in cost. Constitution: Hydrogen gas is introduced from an outer pipeline to the main structure of a recombiner, and when it passes through the vicinity of the central part of the recombiner, it is reacted with copper oxide (CuO 2 ) heated to a temperature more than 300 0 C by a high-frequency heater, and converted gently into water by reduction operation (2H 2 + CuO 2 → Cu + 2H 2 O). The thus prepared water is exhausted through the outer pipeline to a suppression pool. A part of hydrogen gas which has not been converted completely into water by the reaction and is remaining as hydrogen is recovered through exhaust nozzles and again introduced into the main structure of the recombiner. (Yoshino, Y.)

Future product design

DEFF Research Database (Denmark)

Andreasen, Mogens Myrup

1997-01-01

This paper (in form of overheads) formulate new challenges and possibilities for engineering design, utilizing rationalization effect from modularisation, re-use and transparaency.......This paper (in form of overheads) formulate new challenges and possibilities for engineering design, utilizing rationalization effect from modularisation, re-use and transparaency....

Rationally reduced libraries for combinatorial pathway optimization minimizing experimental effort.

Science.gov (United States)

Jeschek, Markus; Gerngross, Daniel; Panke, Sven

2016-03-31

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

Empirical evidence for resource-rational anchoring and adjustment.

Science.gov (United States)

Lieder, Falk; Griffiths, Thomas L; M Huys, Quentin J; Goodman, Noah D

2018-04-01

People's estimates of numerical quantities are systematically biased towards their initial guess. This anchoring bias is usually interpreted as sign of human irrationality, but it has recently been suggested that the anchoring bias instead results from people's rational use of their finite time and limited cognitive resources. If this were true, then adjustment should decrease with the relative cost of time. To test this hypothesis, we designed a new numerical estimation paradigm that controls people's knowledge and varies the cost of time and error independently while allowing people to invest as much or as little time and effort into refining their estimate as they wish. Two experiments confirmed the prediction that adjustment decreases with time cost but increases with error cost regardless of whether the anchor was self-generated or provided. These results support the hypothesis that people rationally adapt their number of adjustments to achieve a near-optimal speed-accuracy tradeoff. This suggests that the anchoring bias might be a signature of the rational use of finite time and limited cognitive resources rather than a sign of human irrationality.

Limited rationality and strategic interaction

DEFF Research Database (Denmark)

Fehr, Ernst; Tyran, Jean-Robert

2008-01-01

Much evidence suggests that people are heterogeneous with regard to their abilities to make rational, forward-looking decisions. This raises the question as to when the rational types are decisive for aggregate outcomes and when the boundedly rational types shape aggregate results. We examine...... this question in the context of a long-standing and important economic problem: the adjustment of nominal prices after an anticipated monetary shock. Our experiments suggest that two types of bounded rationality-money illusion and anchoring-are important behavioral forces behind nominal inertia. However......, depending on the strategic environment, bounded rationality has vastly different effects on aggregate price adjustment. If agents' actions are strategic substitutes, adjustment to the new equilibrium is extremely quick, whereas under strategic complementarity, adjustment is both very slow and associated...

The role of recombination in the emergence of a complex and dynamic HIV epidemic

Directory of Open Access Journals (Sweden)

Morgenstern Burkhard

2010-03-01

Full Text Available Abstract Background Inter-subtype recombinants dominate the HIV epidemics in three geographical regions. To better understand the role of HIV recombinants in shaping the current HIV epidemic, we here present the results of a large-scale subtyping analysis of 9435 HIV-1 sequences that involve subtypes A, B, C, G, F and the epidemiologically important recombinants derived from three continents. Results The circulating recombinant form CRF02_AG, common in West Central Africa, appears to result from recombination events that occurred early in the divergence between subtypes A and G, followed by additional recent recombination events that contribute to the breakpoint pattern defining the current recombinant lineage. This finding also corrects a recent claim that G is a recombinant and a descendant of CRF02, which was suggested to be a pure subtype. The BC and BF recombinants in China and South America, respectively, are derived from recent recombination between contemporary parental lineages. Shared breakpoints in South America BF recombinants indicate that the HIV-1 epidemics in Argentina and Brazil are not independent. Therefore, the contemporary HIV-1 epidemic has recombinant lineages of both ancient and more recent origins. Conclusions Taken together, we show that these recombinant lineages, which are highly prevalent in the current HIV epidemic, are a mixture of ancient and recent recombination. The HIV pandemic is moving towards having increasing complexity and higher prevalence of recombinant forms, sometimes existing as "families" of related forms. We find that the classification of some CRF designations need to be revised as a consequence of (1 an estimated > 5% error in the original subtype assignments deposited in the Los Alamos sequence database; (2 an increasing number of CRFs are defined while they do not readily fit into groupings for molecular epidemiology and vaccine design; and (3 a dynamic HIV epidemic context.

Interpolation of rational matrix functions

CERN Document Server

Ball, Joseph A; Rodman, Leiba

1990-01-01

This book aims to present the theory of interpolation for rational matrix functions as a recently matured independent mathematical subject with its own problems, methods and applications. The authors decided to start working on this book during the regional CBMS conference in Lincoln, Nebraska organized by F. Gilfeather and D. Larson. The principal lecturer, J. William Helton, presented ten lectures on operator and systems theory and the interplay between them. The conference was very stimulating and helped us to decide that the time was ripe for a book on interpolation for matrix valued functions (both rational and non-rational). When the work started and the first partial draft of the book was ready it became clear that the topic is vast and that the rational case by itself with its applications is already enough material for an interesting book. In the process of writing the book, methods for the rational case were developed and refined. As a result we are now able to present the rational case as an indepe...

Decision-Making: Are Plants More Rational than Animals?

Science.gov (United States)

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.

History of Economic Rationalities

DEFF Research Database (Denmark)

This book concentrates upon how economic rationalities have been embedded into particular historical practices, cultures, and moral systems. Through multiple case-studies, situated in different historical contexts of the modern West, the book shows that the development of economic rationalities...... takes place in the meeting with other regimes of thought, values, and moral discourses. The book offers new and refreshing insights, ranging from the development of early economic thinking to economic aspects and concepts in the works of classical thinkers such as Thomas Hobbes, John Locke and Karl Marx......, to the role of economic reasoning in contemporary policies of art and health care. With economic rationalities as the read thread, the reader is offered a unique chance of historical self-awareness and recollection of how economic rationality became the powerful ideological and moral force that it is today....

Genome-wide variation in recombination rate in Eucalyptus.

Science.gov (United States)

Gion, Jean-Marc; Hudson, Corey J; Lesur, Isabelle; Vaillancourt, René E; Potts, Brad M; Freeman, Jules S

2016-08-09

Meiotic recombination is a fundamental evolutionary process. It not only generates diversity, but influences the efficacy of natural selection and genome evolution. There can be significant heterogeneity in recombination rates within and between species, however this variation is not well understood outside of a few model taxa, particularly in forest trees. Eucalypts are forest trees of global economic importance, and dominate many Australian ecosystems. We studied recombination rate in Eucalyptus globulus using genetic linkage maps constructed in 10 unrelated individuals, and markers anchored to the Eucalyptus reference genome. This experimental design provided the replication to study whether recombination rate varied between individuals and chromosomes, and allowed us to study the genomic attributes and population genetic parameters correlated with this variation. Recombination rate varied significantly between individuals (range = 2.71 to 3.51 centimorgans/megabase [cM/Mb]), but was not significantly influenced by sex or cross type (F1 vs. F2). Significant differences in recombination rate between chromosomes were also evident (range = 1.98 to 3.81 cM/Mb), beyond those which were due to variation in chromosome size. Variation in chromosomal recombination rate was significantly correlated with gene density (r = 0.94), GC content (r = 0.90), and the number of tandem duplicated genes (r = -0.72) per chromosome. Notably, chromosome level recombination rate was also negatively correlated with the average genetic diversity across six species from an independent set of samples (r = -0.75). The correlations with genomic attributes are consistent with findings in other taxa, however, the direction of the correlation between diversity and recombination rate is opposite to that commonly observed. We argue this is likely to reflect the interaction of selection and specific genome architecture of Eucalyptus. Interestingly, the differences amongst

Effects of forage ensiling and ration fermentation on total mixed ration pH, ruminal fermentation and performance of growing Holstein-Zebu cross steers.

Science.gov (United States)

Meenongyai, Watcharawit; Pattarajinda, Virote; Stelzleni, Alexander M; Sethakul, Jutarat; Duangjinda, Monchai

2017-09-01

Our objective was to determine the effect of forage ensiling and ration fermentation on total mixed ration pH, ruminal fermentation and animal performance. Thirty Holstein-Zebu cross steers were allotted to feeding treatments for 188 days in a randomized complete block design including: fresh grass-total mixed ration (GTMR; pH 4.7), grass silage-TMR (STMR; pH 4.0) and fermented-TMR (FTMR; pH 3.5). Average daily gain for STMR was greatest during the first 3 months period; however, that for FTMR tended to be greater than GTMR during the second 3 months period (P ruminal NH 3 -N content than STMR. Total volatile fatty acids post-feeding was greatest for GTMR (P Ruminal proportions of acetic and butyric acids were greater for FTMR than GTMR (P ruminal pH. STMR and FTMRs can be used to maintain performance of growing crossbred Holstein steers. © 2017 Japanese Society of Animal Science.

Lewis Base Passivation of Hybrid Halide Perovskites Slows Electron-Hole Recombination: Time-Domain Ab Initio Analysis.

Science.gov (United States)

Liu, Lihong; Fang, Wei-Hai; Long, Run; Prezhdo, Oleg V

2018-03-01

Nonradiative electron-hole recombination plays a key role in determining photon conversion efficiencies in solar cells. Experiments demonstrate significant reduction in the recombination rate upon passivation of methylammonium lead iodide perovskite with Lewis base molecules. Using nonadiabatic molecular dynamics combined with time-domain density functional theory, we find that the nonradiative charge recombination is decelerated by an order of magnitude upon adsorption of the molecules. Thiophene acts by the traditional passivation mechanism, forcing electron density away from the surface. In contrast, pyridine localizes the electron at the surface while leaving it energetically near the conduction band edge. This is because pyridine creates a stronger coordinative bond with a lead atom of the perovskite and has a lower energy unoccupied orbital compared with thiophene due to the more electronegative nitrogen atom relative to thiophene's sulfur. Both molecules reduce two-fold the nonadiabatic coupling and electronic coherence time. A broad range of vibrational modes couple to the electronic subsystem, arising from inorganic and organic components. The simulations reveal the atomistic mechanisms underlying the enhancement of the excited-state lifetime achieved by the perovskite passivation, rationalize the experimental results, and advance our understanding of charge-phonon dynamics in perovskite solar cells.

Psychology and the Rationality of Emotion.

Science.gov (United States)

Clore, Gerald L

2011-04-01

Questions addressed by recent psychological research on emotion include questions about how thought shapes emotion and how emotion, in turn, shapes thought. Research on emotion and cognition paints a somewhat different picture than that seen in traditional discussions of passion and reason. This article reviews several aspects of this research, concentrating specifically on three views of rationality: Rationality as Process, Rationality as Product, and Rationality as Outcome.

Psychology and the Rationality of Emotion*

OpenAIRE

Clore, Gerald L.

2011-01-01

Questions addressed by recent psychological research on emotion include questions about how thought shapes emotion and how emotion, in turn, shapes thought. Research on emotion and cognition paints a somewhat different picture than that seen in traditional discussions of passion and reason. This article reviews several aspects of this research, concentrating specifically on three views of rationality: Rationality as Process, Rationality as Product, and Rationality as Outcome.

Design thinking between rationalism and romanticism

DEFF Research Database (Denmark)

Engholm, Ida; Goldschmidt Salamon, Karen-Lisa

2017-01-01

This article presents a longue durée history of modern design thought, with particular focus on recurrent ideological frictions. Drawing on design history, design anthropology and cultural studies, the authors present an overview of more than 200 years of developments in European and North Americ...

Moral Credentialing and the Rationalization of Misconduct

Science.gov (United States)

Brown, Ryan P.; Tamborski, Michael; Wang, Xiaoqian; Barnes, Collin D.; Mumford, Michael D.; Connelly, Shane; Devenport, Lynn D.

2010-01-01

Recent studies lead to the paradoxical conclusion that the act of affirming one’s egalitarian or pro-social values and virtues might subsequently facilitate prejudiced or self-serving behavior, an effect previously referred to as “moral credentialing.” The present study extends this paradox to the domain of academic misconduct and investigates the hypothesis that such an effect might be limited by the extent to which misbehavior is rationalizable. Using a paradigm designed to investigate deliberative and rationalized forms of cheating (von Hippel, Lakin, & Shakarchi, 2005), we found that when participants had credentialed themselves (versus a non-close acquaintance) via a set of hypothetical moral dilemmas, they were more likely to cheat on a subsequent math task, but only if cheating was highly rationalizable. When cheating was difficult to rationalize, moral credentialing had almost no impact on cheating. PMID:21503267

Testing bounded rationality against full rationality in job changing behavior

OpenAIRE

Contini, Bruno; Morini, Matteo

2007-01-01

In this paper we question the hypothesis of full rationality in the context of job changing behaviour, via simple econometric explorations on microdata drawn from WHIP (Worker Histories Italian Panel). Workers' performance is compared at the end of a three-year time window that starts when choices are expressed, under the accepted notion that the main driving forces of job change are future real wages and expected job quality. Bounded rationality suggests that individuals will search for new ...

Testing Bounded Rationality Against Full Rationality in Job Changing Behavior

OpenAIRE

Bruno Contini

2008-01-01

In this paper I question the hypothesis of full rationality in the context of job changing behaviour, via simple econometric explorations on microdata drawn from WHIP (Worker Histories Italian Panel). Workers’ performance is compared at the end of a three-year time window that starts when choices are expressed, under the accepted notion that the main driving forces of job change are future real wages and expected job quality. Bounded rationality suggests that individuals will search for new o...

Rational design of multifunctional devices based on molybdenum disulfide and graphene hybrid nanostructures

Energy Technology Data Exchange (ETDEWEB)

Lim, Yi Rang; Lee, Young Bum; Kim, Seong Ku; Kim, Seong Jun [Thin Film Materials Research Center, Korea Research Institute of Chemical Technology, Yuseong, Post Office Box 107, Daejeon 305-600 (Korea, Republic of); Kim, Yooseok; Jeon, Cheolho [Nano-Surface Research Group, Korea Basic Science Institute, Daejeon, 302-333 (Korea, Republic of); Song, Wooseok, E-mail: wssong@krict.re.kr [Thin Film Materials Research Center, Korea Research Institute of Chemical Technology, Yuseong, Post Office Box 107, Daejeon 305-600 (Korea, Republic of); Myung, Sung; Lee, Sun Sook; An, Ki-Seok [Thin Film Materials Research Center, Korea Research Institute of Chemical Technology, Yuseong, Post Office Box 107, Daejeon 305-600 (Korea, Republic of); Lim, Jongsun, E-mail: jslim@krict.re.kr [Thin Film Materials Research Center, Korea Research Institute of Chemical Technology, Yuseong, Post Office Box 107, Daejeon 305-600 (Korea, Republic of)

2017-01-15

Highlights: • We fabricated MoS{sub 2}-graphene hybrid thin films for multifunctional applications. • Large-area, uniform multilayer MoS{sub 2} was synthesized on TCVD-grown graphene. • The mobility and photocurrent of the hybrid devices were improved significantly. - Abstract: We rationally designed a new type of hybrid materials, molybdenum disulfide (MoS{sub 2}) synthesized by Mo pre-deposition followed by subsequent sulfurization process directly on thermal chemical vapor deposition (TCVD)-grown graphene, for applications in a multifunctional device. The synthesis of stoichiometric and uniform multilayer MoS{sub 2} and high-crystalline monolayer graphene was evaluated by X-ray photoelectron spectroscopy and Raman spectroscopy. To examine the electrical transport and photoelectrical properties of MoS{sub 2}-graphene hybrid films, field effect transistors (FETs) and visible-light photodetectors based on MoS{sub 2}-graphene were both fabricated. As a result, the extracted mobility for MoS{sub 2}-graphene hybrid FETs was two times higher than that of MoS{sub 2} FETs. In addition, the MoS{sub 2}-graphene photodetectors revealed a significant photocurrent with abrupt switching behavior under periodic illumination.

Looking for the optimal rate of recombination for evolutionary dynamics

Science.gov (United States)

Saakian, David B.

2018-01-01

We consider many-site mutation-recombination models of evolution with selection. We are looking for situations where the recombination increases the mean fitness of the population, and there is an optimal recombination rate. We found two fitness landscapes supporting such nonmonotonic behavior of the mean fitness versus the recombination rate. The first case is related to the evolution near the error threshold on a neutral-network-like fitness landscape, for moderate genome lengths and large population. The more realistic case is the second one, in which we consider the evolutionary dynamics of a finite population on a rugged fitness landscape (the smooth fitness landscape plus some random contributions to the fitness). We also give the solution to the horizontal gene transfer model in the case of asymmetric mutations. To obtain nonmonotonic behavior for both mutation and recombination, we need a specially designed (ideal) fitness landscape.

Psychology and the Rationality of Emotion*

Science.gov (United States)

Clore, Gerald L.

2014-01-01

Questions addressed by recent psychological research on emotion include questions about how thought shapes emotion and how emotion, in turn, shapes thought. Research on emotion and cognition paints a somewhat different picture than that seen in traditional discussions of passion and reason. This article reviews several aspects of this research, concentrating specifically on three views of rationality: Rationality as Process, Rationality as Product, and Rationality as Outcome. PMID:25125770

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

Science.gov (United States)

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.

DISTRIBUTED RC NETWORKS WITH RATIONAL TRANSFER FUNCTIONS,

Science.gov (United States)

A distributed RC circuit analogous to a continuously tapped transmission line can be made to have a rational short-circuit transfer admittance and...one rational shortcircuit driving-point admittance. A subcircuit of the same structure has a rational open circuit transfer impedance and one rational ...open circuit driving-point impedance. Hence, rational transfer functions may be obtained while considering either generator impedance or load

Rational Design of in Vivo Tau Tangle-Selective Near-Infrared Fluorophores: Expanding the BODIPY Universe.

Science.gov (United States)

Verwilst, Peter; Kim, Hye-Ri; Seo, Jinho; Sohn, Nak-Won; Cha, Seung-Yun; Kim, Yeongmin; Maeng, Sungho; Shin, Jung-Won; Kwak, Jong Hwan; Kang, Chulhun; Kim, Jong Seung

2017-09-27

The elucidation of the cause of Alzheimer's disease remains one of the greatest questions in neurodegenerative research. The lack of highly reliable low-cost sensors to study the structural changes in key proteins during the progression of the disease is a contributing factor to this lack of insight. In the current work, we describe the rational design and synthesis of two fluorescent BODIPY-based probes, named Tau 1 and Tau 2. The probes were evaluated on the molecular surface formed by a fibril of the PHF6 ( 306 VQIVYK 311 ) tau fragment using molecular docking studies to provide a potential molecular model to rationalize the selectivity of the new probes as compared to a homologous Aβ-selective probe. The probes were synthesized in a few steps from commercially available starting products and could thus prove to be highly cost-effective. We demonstrated the excellent photophysical properties of the dyes, such as a large Stokes shift and emission in the near-infrared window of the electromagnetic spectrum. The probes demonstrated a high selectivity for self-assembled microtubule-associated protein tau (Tau protein), in both solution and cell-based experiments. Moreover, the administration to an acute murine model of tauopathy clearly revealed the staining of self-assembled hyperphosphorylated tau protein in pathologically relevant hippocampal brain regions. Tau 1 demonstrated efficient blood-brain barrier penetrability and demonstrated a clear selectivity for tau tangles over Aβ plaques, as well as the capacity for in vivo imaging in a transgenic mouse model. The current work could open up avenues for the cost-effective monitoring of the tau protein aggregation state in animal models as well as tissue staining. Furthermore, these fluorophores could serve as the basis for the development of clinically relevant sensors, for example based on PET imaging.

Final Report: Rational Design of Wide Band Gap Buffer Layers for High-Efficiency Thin-Film Photovoltaics

Energy Technology Data Exchange (ETDEWEB)

Lordi, Vincenzo [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2016-09-30

The main objective of this project is to enable rational design of wide band gap buffer layer materials for CIGS thin-film PV by building understanding of the correlation of atomic-scale defects in the buffer layer and at the buffer/absorber interface with device electrical properties. Optimized wide band gap buffers are needed to reduce efficiency loss from parasitic absorption in the buffer. The approach uses first-principles materials simulations coupled with nanoscale analytical electron microscopy as well as device electrical characterization. Materials and devices are produced by an industrial partner in a manufacturing line to maximize relevance, with the goal of enabling R&D of new buffer layer compositions or deposition processes to push device efficiencies above 21%. Cadmium sulfide (CdS) is the reference material for analysis, as the prototypical high-performing buffer material.

Rational design of single-ion magnets and spin qubits based on mononuclear lanthanoid complexes.

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Baldoví, José J; Cardona-Serra, Salvador; Clemente-Juan, Juan M; Coronado, Eugenio; Gaita-Ariño, Alejandro; Palii, Andrew

2012-11-19

Here we develop a general approach to calculating the energy spectrum and the wave functions of the low-lying magnetic levels of a lanthanoid ion submitted to the crystal field created by the surrounding ligands. This model allows us to propose general criteria for the rational design of new mononuclear lanthanoid complexes behaving as single-molecule magnets (SMMs) or acting as robust spin qubits. Three typical environments exhibited by these metal complexes are considered, namely, (a) square antiprism, (b) triangular dodecahedron, and (c) trigonal prism. The developed model is used to explain the properties of some representative examples showing these geometries. Key questions in this area, such as the chemical tailoring of the superparamagnetic energy barrier, tunneling gap, or spin relaxation time, are discussed. Finally, in order to take into account delocalization and/or covalent effects of the ligands, this point-charge model is complemented with ab initio calculations, which provide accurate information on the charge distribution around the metal, allowing for an explanation of the SMM behavior displayed by some sandwich-type organometallic compounds.

Production and Energy Partition of Lactating Dairy Goats Fed Rations Containing Date Fruit Waste

Directory of Open Access Journals (Sweden)

E. Yuniarti

2016-04-01

Full Text Available Dates fruit waste (DFW is a by-product of dates juice industry that contains high energy. So, it is suitable for an energy source in dairy goat ration. This study was conducted to observe the effect of DFW utilization in the ration on energy partition and productivity of lactating dairy goats. The experimental design was randomized block design using 9 primiparous lactating dairy goats. There were three types of ration as treatments used in this study, i.e. R0= 35% forage + 65% concentrate, R1= 35% forage + 55% concentrate + 10% DFW, and R2= 35% forage + 45% concentrate + 20% DFW. Data were analyzed using ANOVA and polynomial orthogonal test. The evaluated variables were dry matter intake (DMI, energy partition including energy intake, digestible and metabolizable energy, fecal and urine energy, energy in methane gas, and energy in milk, milk production and quality. The results showed that the linear decreased of DMI, energy intake, digestible energy, metabolizable energy, and urine energy with the increased of DFW level in the rations. The use of 10% DFW (R1 showed the lowest energy loss through feces and methane gas of all treatments about 1089.57 kcal/head/d and 2.36 kcal/head/d, respectively. The use of DFW did not affect energy retention in milk. The utilization of DFW in ration did not significantly prevent the decline of milk production and milk quality. It can be concluded that DFW can be used as an alternative feed for the lactating dairy goat up to 10% in the ration.

Rational design and validation of an anti-protein kinase C active-state specific antibody based on conformational changes.

Science.gov (United States)

Pena, Darlene Aparecida; Andrade, Victor Piana de; Silva, Gabriela Ávila Fernandes; Neves, José Ivanildo; Oliveira, Paulo Sergio Lopes de; Alves, Maria Julia Manso; Devi, Lakshmi A; Schechtman, Deborah

2016-02-25

Protein kinase C (PKC) plays a regulatory role in key pathways in cancer. However, since phosphorylation is a step for classical PKC (cPKC) maturation and does not correlate with activation, there is a lack of tools to detect active PKC in tissue samples. Here, a structure-based rational approach was used to select a peptide to generate an antibody that distinguishes active from inactive cPKC. A peptide conserved in all cPKCs, C2Cat, was chosen since modeling studies based on a crystal structure of PKCβ showed that it is localized at the interface between the C2 and catalytic domains of cPKCs in an inactive kinase. Anti-C2Cat recognizes active cPKCs at least two-fold better than inactive kinase in ELISA and immunoprecipitation assays, and detects the temporal dynamics of cPKC activation upon receptor or phorbol stimulation. Furthermore, the antibody is able to detect active PKC in human tissue. Higher levels of active cPKC were observed in the more aggressive triple negative breast cancer tumors as compared to the less aggressive estrogen receptor positive tumors. Thus, this antibody represents a reliable, hitherto unavailable and a valuable tool to study PKC activation in cells and tissues. Similar structure-based rational design strategies can be broadly applied to obtain active-state specific antibodies for other signal transduction molecules.

Max Weber's Types of Rationality: Cornerstones for the Analysis of Rationalization Processes in History.

Science.gov (United States)

Kalberg, Stephen

1980-01-01

Explores rationality in Max Weber's works and identifies four types of rationality which play major roles in his writing--practical, theoretical, substantive, and formal. Implications for society and education are discussed. (DB)

Performance characterization of hydrogen isotope exchange and recombination catalysts for tritium processing

International Nuclear Information System (INIS)

Suppiah, S.; Ryland, D.; Marcinkowska, K.; Boniface, H.; Everatt, A.

2010-01-01

AECL's hydrogen isotope exchange catalyst and recombination catalysts have been successfully applied to a wide range of industrial tritium-removal applications. The catalysts are used for Liquid Phase Catalytic Exchange (LPCE) and for gas-phase and trickle-bed recombination of hydrogen isotopes and have led to process simplification, improved safety and operational advantages. Catalyst performance design equations derived from laboratory testing of these catalysts have been validated against performance under industrial conditions. In a Combined Electrolysis and Catalytic Exchange (CECE) demonstration plant analyses of LPCE and recombiner efficiency were carried out as a function of catalyst activity over a wide range of operation. A steady-state process simulation used to model and design the hydrogen-water isotopic exchange processes, such as the CECE detritiation plant, was validated using the results of this demonstration. Catalyst development for isotope-exchange and recombination applications has continued over the last decade. As a result, significant improvements in catalyst performance have been achieved for these applications. This paper outlines the uniqueness of AECL's specialized catalysts and process designs for these applications with examples from laboratory and industrial case studies.

Genome-wide recombination rate variation in a recombination map of cotton.

Science.gov (United States)

Shen, Chao; Li, Ximei; Zhang, Ruiting; Lin, Zhongxu

2017-01-01

Recombination is crucial for genetic evolution, which not only provides new allele combinations but also influences the biological evolution and efficacy of natural selection. However, recombination variation is not well understood outside of the complex species' genomes, and it is particularly unclear in Gossypium. Cotton is the most important natural fibre crop and the second largest oil-seed crop. Here, we found that the genetic and physical maps distances did not have a simple linear relationship. Recombination rates were unevenly distributed throughout the cotton genome, which showed marked changes along the chromosome lengths and recombination was completely suppressed in the centromeric regions. Recombination rates significantly varied between A-subgenome (At) (range = 1.60 to 3.26 centimorgan/megabase [cM/Mb]) and D-subgenome (Dt) (range = 2.17 to 4.97 cM/Mb), which explained why the genetic maps of At and Dt are similar but the physical map of Dt is only half that of At. The translocation regions between A02 and A03 and between A04 and A05, and the inversion regions on A10, D10, A07 and D07 indicated relatively high recombination rates in the distal regions of the chromosomes. Recombination rates were positively correlated with the densities of genes, markers and the distance from the centromere, and negatively correlated with transposable elements (TEs). The gene ontology (GO) categories showed that genes in high recombination regions may tend to response to environmental stimuli, and genes in low recombination regions are related to mitosis and meiosis, which suggested that they may provide the primary driving force in adaptive evolution and assure the stability of basic cell cycle in a rapidly changing environment. Global knowledge of recombination rates will facilitate genetics and breeding in cotton.

The concept of rational suicide.

Science.gov (United States)

Mayo, D J

1986-05-01

Suicide has been condemned in our culture in one way or another since Augustine offered theological arguments against it in the sixth century. More recently, theological condemnation has given way to the view that suicidal behavior must always be symptomatic of emotional disturbance and mental illness. However, suicide has not always been viewed so negatively. In other times and cultures, it has been held that circumstances might befall a person in which suicide would be a perfectly rational course of action, in the same sense that any other course of action could be rational: that it could be sensible, i.e., defensible by good reasons, or that it could be in keeping with the agent's fundamental interests. Indiscriminate use of modern life-sustaining technologies has renewed interest in the possibility of rational suicide. Today proponents of rational suicide tend to equate the rationality of suicide with the competence of the decision to commit suicide.

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

Science.gov (United States)

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.

Rational Ligand Design for U(VI) and Pu(IV)

International Nuclear Information System (INIS)

Szigethy, Geza

2009-01-01

Nuclear power is an attractive alternative to hydrocarbon-based energy production at a time when moving away from carbon-producing processes is widely accepted as a significant developmental need. Hence, the radioactive actinide power sources for this industry are necessarily becoming more widespread, which is accompanied by the increased risk of exposure to both biological and environmental systems. This, in turn, requires the development of technology designed to remove such radioactive threats efficiently and selectively from contaminated material, whether that be contained nuclear waste streams or the human body. Raymond and coworkers (University of California, Berkeley) have for decades investigated the interaction of biologically-inspired, hard Lewis-base ligands with high-valent, early-actinide cations. It has been established that such ligands bind strongly to the hard Lewis-acidic early actinides, and many poly-bidentate ligands have been developed and shown to be effective chelators of actinide contaminants in vivo. Work reported herein explores the effect of ligand geometry on the linear U(IV) dioxo dication (uranyl, UO 2 2+ ). The goal is to utilize rational ligand design to develop ligands that exhibit shape selectivity towards linear dioxo cations and provides thermodynamically favorable binding interactions. The uranyl complexes with a series of tetradentate 3-hydroxy-pyridin-2-one (3,2-HOPO) ligands were studied in both the crystalline state as well as in solution. Despite significant geometric differences, the uranyl affinities of these ligands vary only slightly but are better than DTPA, the only FDA-approved chelation therapy for actinide contamination. The terepthalamide (TAM) moiety was combined into tris-beidentate ligands with 1,2- and 3,2-HOPO moieties were combined into hexadentate ligands whose structural preferences and solution thermodynamics were measured with the uranyl cation. In addition to achieving coordinative saturation, these

Rational Ligand Design for U(VI) and Pu(IV)

Energy Technology Data Exchange (ETDEWEB)

Szigethy, Geza [Univ. of California, Berkeley, CA (United States)

2009-08-12

Nuclear power is an attractive alternative to hydrocarbon-based energy production at a time when moving away from carbon-producing processes is widely accepted as a significant developmental need. Hence, the radioactive actinide power sources for this industry are necessarily becoming more widespread, which is accompanied by the increased risk of exposure to both biological and environmental systems. This, in turn, requires the development of technology designed to remove such radioactive threats efficiently and selectively from contaminated material, whether that be contained nuclear waste streams or the human body. Raymond and coworkers (University of California, Berkeley) have for decades investigated the interaction of biologically-inspired, hard Lewis-base ligands with high-valent, early-actinide cations. It has been established that such ligands bind strongly to the hard Lewis-acidic early actinides, and many poly-bidentate ligands have been developed and shown to be effective chelators of actinide contaminants in vivo. Work reported herein explores the effect of ligand geometry on the linear U(IV) dioxo dication (uranyl, UO₂ ²⁺). The goal is to utilize rational ligand design to develop ligands that exhibit shape selectivity towards linear dioxo cations and provides thermodynamically favorable binding interactions. The uranyl complexes with a series of tetradentate 3-hydroxy-pyridin-2-one (3,2-HOPO) ligands were studied in both the crystalline state as well as in solution. Despite significant geometric differences, the uranyl affinities of these ligands vary only slightly but are better than DTPA, the only FDA-approved chelation therapy for actinide contamination. The terepthalamide (TAM) moiety was combined into tris-beidentate ligands with 1,2- and 3,2-HOPO moieties were combined into hexadentate ligands whose structural preferences and solution thermodynamics were measured with the uranyl cation. In addition to achieving coordinative

Fine-Scale Recombination Maps of Fungal Plant Pathogens Reveal Dynamic Recombination Landscapes and Intragenic Hotspots.

Science.gov (United States)

Stukenbrock, Eva H; Dutheil, Julien Y

2018-03-01

Meiotic recombination is an important driver of evolution. Variability in the intensity of recombination across chromosomes can affect sequence composition, nucleotide variation, and rates of adaptation. In many organisms, recombination events are concentrated within short segments termed recombination hotspots. The variation in recombination rate and positions of recombination hotspot can be studied using population genomics data and statistical methods. In this study, we conducted population genomics analyses to address the evolution of recombination in two closely related fungal plant pathogens: the prominent wheat pathogen Zymoseptoria tritici and a sister species infecting wild grasses Z. ardabiliae We specifically addressed whether recombination landscapes, including hotspot positions, are conserved in the two recently diverged species and if recombination contributes to rapid evolution of pathogenicity traits. We conducted a detailed simulation analysis to assess the performance of methods of recombination rate estimation based on patterns of linkage disequilibrium, in particular in the context of high nucleotide diversity. Our analyses reveal overall high recombination rates, a lack of suppressed recombination in centromeres, and significantly lower recombination rates on chromosomes that are known to be accessory. The comparison of the recombination landscapes of the two species reveals a strong correlation of recombination rate at the megabase scale, but little correlation at smaller scales. The recombination landscapes in both pathogen species are dominated by frequent recombination hotspots across the genome including coding regions, suggesting a strong impact of recombination on gene evolution. A significant but small fraction of these hotspots colocalize between the two species, suggesting that hotspot dynamics contribute to the overall pattern of fast evolving recombination in these species. Copyright © 2018 Stukenbrock and Dutheil.

RATGRAPH: Computer Graphing of Rational Functions.

Science.gov (United States)

Minch, Bradley A.

1987-01-01

Presents an easy-to-use Applesoft BASIC program that graphs rational functions and any asymptotes that the functions might have. Discusses the nature of rational functions, graphing them manually, employing a computer to graph rational functions, and describes how the program works. (TW)

F-theory and all things rational: surveying U(1) symmetries with rational sections

International Nuclear Information System (INIS)

Lawrie, Craig; Schäfer-Nameki, Sakura; Wong, Jin-Mann

2015-01-01

We study elliptic fibrations for F-theory compactifications realizing 4d and 6d supersymmetric gauge theories with abelian gauge factors. In the fibration these U(1) symmetries are realized in terms of additional rational section. We obtain a universal characterization of all the possible U(1) charges of matter fields by determining the corresponding codimension two fibers with rational sections. In view of modelling supersymmetric Grand Unified Theories, one of the main examples that we analyze are U(1) symmetries for SU(5) gauge theories with 5̄ and 10 matter. We use a combination of constraints on the normal bundle of rational curves in Calabi-Yau three- and four-folds, as well as the splitting of rational curves in the fibers in codimension two, to determine the possible configurations of smooth rational sections. This analysis straightforwardly generalizes to multiple U(1)s. We study the flops of such fibers, as well as some of the Yukawa couplings in codimension three. Furthermore, we carry out a universal study of the U(1)-charged GUT singlets, including their KK-charges, and determine all realizations of singlet fibers. By giving vacuum expectation values to these singlets, we propose a systematic way to analyze the Higgsing of U(1)s to discrete gauge symmetries in F-theory.

"Leaky" Rationality: How Research on Behavioral Decision Making Challenges Normative Standards of Rationality.

Science.gov (United States)

Keys, Daniel J; Schwartz, Barry

2007-06-01

For more than 30 years, decision-making research has documented that people often violate various principles of rationality, some of which are so fundamental that theorists of rationality rarely bother to state them. We take these characteristics of decision making as a given but argue that it is problematic to conclude that they typically represent departures from rationality. The very psychological processes that lead to "irrational" decisions (e.g., framing, mental accounting) continue to exert their influence when one experiences the results of the decisions. That is, psychological processes that affect decisions may be said also to "leak" into one's experience. The implication is that formal principles of rationality do not provide a good enough normative standard against which to assess decision making. Instead, what is needed is a substantive theory of rationality-one that takes subjective experience seriously, considers both direct and indirect consequences of particular decisions, considers how particular decisions fit into life as a whole, and considers the effects of decisions on others. Formal principles may play a role as approximations of the substantive theory that can be used by theorists and decision makers in cases in which the formal principles can capture most of the relevant considerations and leakage into experience is negligible. © 2007 Association for Psychological Science.

Popper, Rationality and the Possibility of Social Science

Directory of Open Access Journals (Sweden)

Danny Frederick

2013-02-01

Full Text Available Social science employs teleological explanations which depend upon the rationality principle, according to which people exhibit instrumental rationality. Popper points out that people also exhibit critical rationality, the tendency to stand back from, and to question or criticise, their views. I explain how our critical rationality impugns the explanatory value of the rationality principle and thereby threatens the very possibility of social science. I discuss the relationship between instrumental and critical rationality and show how we can reconcile our critical rationality with the possibility of social science if we invoke Popper’s conception of limited rationality and his indeterminism.

Ethics of rationing of nursing care.

Science.gov (United States)

Rooddehghan, Zahra; Yekta, Zohreh Parsa; Nasrabadi, Alireza N

2016-09-21

Rationing of various needed services, for example, nursing care, is inevitable due to unlimited needs and limited resources. Rationing of nursing care is considered an ethical issue since it requires judgment about potential conflicts between personal and professional values. The present research sought to explore aspects of rationing nursing care in Iran. This study applied qualitative content analysis, a method to explore people's perceptions of everyday life phenomena and interpret the subjective content of text data. Data collection was performed through in-depth, unstructured, face-to-face interviews with open-ended questions. The study population included Iranian nurses of all nursing positions, from clinical nurses to nurse managers. Purposive sampling was employed to select 15 female and 3 male nurses (11 clinical nurses, 3 supervisors, 1 matron, 1 nurse, and 2 members of the Nursing Council) working in hospitals of three cities in Iran. The study protocol was approved by Tehran University of Medical Sciences (91D1302870). Written informed consent was also obtained from all participants. According to the participants, rationing of nursing care consisted of two categories, that is, causes of rationing and consequences of rationing. The first category comprised three subcategories, namely, patient needs and demands, routinism, and VIP patients. The three subcategories forming the second category were missed nursing care, patient dissatisfaction, and nurses' feeling of guilt. Levels at which healthcare practices are rationed and clarity of the rationing are important structural considerations in the development of an equal, appropriate, and ethical healthcare system. Moreover, the procedure of rationing is critical as it not only influences people's lives but also reflects the values that dominate in the society. Therefore, in order to minimize the negative consequences of rationing of nursing care, further studies on the ethical dimensions of this phenomenon

Casebook on rationalization of power use

International Nuclear Information System (INIS)

1986-06-01

This book introduces the cases on rationalization of power use, which is divided into four parts. The first part refers the goal of rational use of energy and the result. The second part deals with the excellent cases on rationalization of domestic power use, which list the name of the company, hotel and factory according to the field such as building, textile and food. The third part contains the outstanding cases on rationalization of foreign power use, which were listed by the specific way to reduce electricity use each section. The fourth part is comprised of two chapters, which deals with the cases of domestic technical data and foreign technical data for rational use of energy.

Recombinant polymorphic membrane protein D in combination with a novel, second-generation lipid adjuvant protects against intra-vaginal Chlamydia trachomatis infection in mice.

Science.gov (United States)

Paes, Wayne; Brown, Naj; Brzozowski, Andrzej M; Coler, Rhea; Reed, Steve; Carter, Darrick; Bland, Martin; Kaye, Paul M; Lacey, Charles J N

2016-07-29

The development of a chlamydial vaccine that elicits protective mucosal immunity is of paramount importance in combatting the global spread of sexually transmitted Chlamydia trachomatis (Ct) infections. While the identification and prioritization of chlamydial antigens is a crucial prerequisite for efficacious vaccine design, it is likely that novel adjuvant development and selection will also play a pivotal role in the translational potential of preclinical Ct vaccines. Although the molecular nature of the immuno-modulatory component is of primary importance, adjuvant formulation and delivery systems may also govern vaccine efficacy and potency. Our study provides the first preclinical evaluation of recombinant Ct polymorphic membrane protein D (rPmpD) in combination with three different formulations of a novel second-generation lipid adjuvant (SLA). SLA was rationally designed in silico by modification of glucopyranosyl lipid adjuvant (GLA), a TLR4 agonistic precursor molecule currently in Phase II clinical development. We demonstrate robust protection against intra-vaginal Ct challenge in mice, evidenced by significantly enhanced resistance to infection and reduction in mean bacterial load. Strikingly, protection was found to correlate with the presence of robust anti-rPmpD serum and cervico-vaginal IgG titres, even in the absence of adjuvant-induced Th1-type cellular immune responses elicited by each SLA formulation, and we further show that anti-rPmpD antibodies recognize Ct EBs. These findings highlight the utility of SLA and rational molecular design of adjuvants in preclinical Ct vaccine development, but also suggest an important role for anti-rPmpD antibodies in protection against urogenital Ct infection. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Emergence of recombinant forms in geographic regions with co-circulating HIV subtypes in the dynamic HIV-1 epidemic

Energy Technology Data Exchange (ETDEWEB)

Zhang, Ming [Los Alamos National Laboratory; Letiner, Thomas K [Los Alamos National Laboratory; Korber, Bette T [Los Alamos National Laboratory; Foley, Brian [Los Alamos National Laboratory

2009-01-01

We have reexamined the subtype designations of {approx}10,000 subtype A, B, C, G, and AG, BC, BF recombinant sequences, and compared the results of the new analysis with their published designations. Intersubtype recombinants dominate HIV epidemics in three different geographical regions. The circulating recombinant from (CRF) CRF02-AG, common in West Central Africa, appears to result from a recombination event that occurred early in the divergence between subtypes A and G, although additional more recent recombination events may have contributed to the breakpoint pattern in this recombinant lineage as well. The Chinese recombinant epidemic strains CRF07 and CRF08, in contrast, result from recent recombinations between more contemporary strains. Nevertheless, CRF07 and CRF08 contributed to many subsequent recombination events. The BF recombinant epidemics in two HIV-1 epicenters in South America are not independent and BF epidemics in South America have an unusually high fraction of unique recombinant forms (URFs) that have each been found only once and carry distinctive breakpoints. Taken together, these analyses reveal a complex and dynamic picture of the current HIV-1 epidemic, and suggest a means of grouping and tracking relationships between viruses through preservation of shared breakpints.

Rational Design of a New Trypanosoma rangeli Trans-Sialidase for Efficient Sialylation of Glycans

DEFF Research Database (Denmark)

Jers, Carsten; Michalak, Malwina; Larsen, Dorte Møller

2014-01-01

This paper reports rational engineering of Trypanosoma rangeli sialidase to develop an effective enzyme for a potentially important type of reactivity: production of sialylated prebiotic glycans. The Trypanosoma cruzi trans-sialidase and the homologous T. rangeli sialidase has previously been use...

From rational creatures to the rational Creator: ancient and patristic analogies of the “fine-tuning” argument

Directory of Open Access Journals (Sweden)

Alexey Fokin

2017-12-01

Full Text Available In this article the author deals with the proofs of the existence of God, based on the fact of the presence of rational beings in the world. These proofs can be found in Greek and Roman Classical philosophy and early Patristics, and can be viewed as an analogue of the modern “fine-tuning argument”. The author considers the origins and development of this argument in the Greek and Roman philosophy: in Socrates, Plato, Cicero, Sextus Empiricus, and especially the Stoics, who gave to the argument a logical form, based on the relationship between “the parts and the whole”: if the world as a whole produces and contains rational beings as its parts, it should also be rational or contain a rational principle that generates all its parts and governs them, just as human soul governs human body. The correction of this argument was proposed by Sextus Empiricus, who introduced the concept of "spermatic logoi", or rational principles, to explain the generation of the rational beings by the world, so that if the world contains the spermatic logoi of rational and living beings, then the world as a whole is also rational. The author also investigates the reception of the argument based on the existence of rational beings in the world in Latin Patristics: in Minucius Felix, Tertullian and especially Lactantius, in whom this argument has reached the climax of its development. At the same time it was shown, that the ancient argument has undergone a transformation from the postulation of the rationality of the world as a whole or its equation with God himself to a genuine proof of the existence of the one God who is the Creator both of the world and human beings, superior to the both as the all-powerful and transcendent Mind.

Thermodynamic dissection of the binding energetics of proline-rich peptides to the Abl-SH3 domain: implications for rational ligand design.

Science.gov (United States)

Palencia, Andrés; Cobos, Eva S; Mateo, Pedro L; Martínez, Jose C; Luque, Irene

2004-02-13

The inhibition of the interactions between SH3 domains and their targets is emerging as a promising therapeutic strategy. To date, rational design of potent ligands for these domains has been hindered by the lack of understanding of the origins of the binding energy. We present here a complete thermodynamic analysis of the binding energetics of the p41 proline-rich decapeptide (APSYSPPPPP) to the SH3 domain of the c-Abl oncogene. Isothermal titration calorimetry experiments have revealed a thermodynamic signature for this interaction (very favourable enthalpic contributions opposed by an unfavourable binding entropy) inconsistent with the highly hydrophobic nature of the p41 ligand and the Abl-SH3 binding site. Our structural and thermodynamic analyses have led us to the conclusion, having once ruled out any possible ionization events or conformational changes coupled to the association, that the establishment of a complex hydrogen-bond network mediated by water molecules buried at the binding interface is responsible for the observed thermodynamic behaviour. The origin of the binding energetics for proline-rich ligands to the Abl-SH3 domain is further investigated by a comparative calorimetric analysis of a set of p41-related ligands. The striking effects upon the enthalpic and entropic contributions provoked by conservative substitutions at solvent-exposed positions in the ligand confirm the complexity of the interaction. The implications of these results for rational ligand design are discussed.

Rationing medical education | Walsh | African Health Sciences

African Journals Online (AJOL)

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 ...

Designing and testing broadly-protective filoviral vaccines optimized for cytotoxic T-lymphocyte epitope coverage.

Directory of Open Access Journals (Sweden)

Paul W Fenimore

Full Text Available We report the rational design and in vivo testing of mosaic proteins for a polyvalent pan-filoviral vaccine using a computational strategy designed for the Human Immunodeficiency Virus type 1 (HIV-1 but also appropriate for Hepatitis C virus (HCV and potentially other diverse viruses. Mosaics are sets of artificial recombinant proteins that are based on natural proteins. The recombinants are computationally selected using a genetic algorithm to optimize the coverage of potential cytotoxic T lymphocyte (CTL epitopes. Because evolutionary history differs markedly between HIV-1 and filoviruses, we devised an adapted computational technique that is effective for sparsely sampled taxa; our first significant result is that the mosaic technique is effective in creating high-quality mosaic filovirus proteins. The resulting coverage of potential epitopes across filovirus species is superior to coverage by any natural variants, including current vaccine strains with demonstrated cross-reactivity. The mosaic cocktails are also robust: mosaics substantially outperformed natural strains when computationally tested against poorly sampled species and more variable genes. Furthermore, in a computational comparison of cross-reactive potential a design constructed prior to the Bundibugyo outbreak performed nearly as well against all species as an updated design that included Bundibugyo. These points suggest that the mosaic designs would be more resilient than natural-variant vaccines against future Ebola outbreaks dominated by novel viral variants. We demonstrate in vivo immunogenicity and protection against a heterologous challenge in a mouse model. This design work delineates the likely requirements and limitations on broadly-protective filoviral CTL vaccines.

Designing and testing broadly-protective filoviral vaccines optimized for cytotoxic T-lymphocyte epitope coverage.

Science.gov (United States)

Fenimore, Paul W; Muhammad, Majidat A; Fischer, William M; Foley, Brian T; Bakken, Russell R; Thurmond, James R; Yusim, Karina; Yoon, Hyejin; Parker, Michael; Hart, Mary Kate; Dye, John M; Korber, Bette; Kuiken, Carla

2012-01-01

We report the rational design and in vivo testing of mosaic proteins for a polyvalent pan-filoviral vaccine using a computational strategy designed for the Human Immunodeficiency Virus type 1 (HIV-1) but also appropriate for Hepatitis C virus (HCV) and potentially other diverse viruses. Mosaics are sets of artificial recombinant proteins that are based on natural proteins. The recombinants are computationally selected using a genetic algorithm to optimize the coverage of potential cytotoxic T lymphocyte (CTL) epitopes. Because evolutionary history differs markedly between HIV-1 and filoviruses, we devised an adapted computational technique that is effective for sparsely sampled taxa; our first significant result is that the mosaic technique is effective in creating high-quality mosaic filovirus proteins. The resulting coverage of potential epitopes across filovirus species is superior to coverage by any natural variants, including current vaccine strains with demonstrated cross-reactivity. The mosaic cocktails are also robust: mosaics substantially outperformed natural strains when computationally tested against poorly sampled species and more variable genes. Furthermore, in a computational comparison of cross-reactive potential a design constructed prior to the Bundibugyo outbreak performed nearly as well against all species as an updated design that included Bundibugyo. These points suggest that the mosaic designs would be more resilient than natural-variant vaccines against future Ebola outbreaks dominated by novel viral variants. We demonstrate in vivo immunogenicity and protection against a heterologous challenge in a mouse model. This design work delineates the likely requirements and limitations on broadly-protective filoviral CTL vaccines.

Rationality and antiemotionality as a risk factor for cancer: concept differentiation.

Science.gov (United States)

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.

Effects of Rational-Emotive Therapy, Rational Role Reversal, and Rational-Emotive Imagery on the Emotional Adjustment of Community Mental Health Center Patients.

Science.gov (United States)

Lipsky, Marc J.; And Others

1980-01-01

Results showed that rational-emotive therapy (RET), with the addition of rational role reversal, produced significantly better results than did relaxation training and support or no contact. This was the first study to demonstrate the efficacy of RET with multisymptomatic applicants to a community mental health center. (Author/BEF)

Argumentation, rationality, and psychology of reasoning

Directory of Open Access Journals (Sweden)

David Godden

2015-05-01

Full Text Available This paper explicates an account of argumentative rationality by articulating the common, basic idea of its nature, and then identifying a collection of assumptions inherent in it. Argumentative rationality is then contrasted with dual-process theories of reasoning and rationality prevalent in the psychology of reasoning. It is argued that argumentative rationality properly corresponds only with system-2 reasoning in dual-process theories. This result challenges the prescriptive force of argumentative norms derives if they derive at all from their descriptive accuracy of our cognitive capacities. In response, I propose an activity-based account of reasoning which retains the assumptions of argumentative rationality while recontextualizing the relationship between reasoning as a justificatory activity and the psychological states and processes underlying that activity.

Genetic Recombination

Science.gov (United States)

Whitehouse, H. L. K.

1973-01-01

Discusses the mechanisms of genetic recombination with particular emphasis on the study of the fungus Sordaria brevicollis. The study of recombination is facilitated by the use of mutants of this fungus in which the color of the ascospores is affected. (JR)

Rational design of molecularly imprinted polymer: the choice of cross-linker.

Science.gov (United States)

Muhammad, Turghun; Nur, Zohre; Piletska, Elena V; Yimit, Osmanjan; Piletsky, Sergey A

2012-06-07

The paper describes a rational approach for the selection of cross-linkers during the development of molecularly imprinted polymers (MIPs). As a model system for this research MIPs specific for the drug zidovudine (AZT) were designed and tested. Three cross-linkers trimethylolpropane trimethacrylate (TRIM), ethylene glycol dimethacrylate (EGDMA) and divinylbenzene (DVB) were studied. The analogue of zidovudine (AZT) ester (AZT-ES) was used as a dummy template. The imprinting factors for all of the polymers in the static adsorption experiments were calculated. The data on the AZT adsorption by control polymers (CP), which were prepared with different cross-linkers without a functional monomer, was also analyzed. DVB was found to be more inert towards zidovudine than EGDMA and TRIM, which was confirmed by both molecular modelling and adsorption experiments. It was demonstrated that DVB-based polymers had a higher imprinting factor (I = 1.85) compared with other tested cross-linked polymers. It was suggested that the selection of the cross-linker should be based on the strength of the interaction with the template: the cross-linker which displays lower binding of the template should be preferential because it generates MIPs with lower non-specific binding and a higher imprinting factor, and therefore specificity. Which cross-linker to use for the preparation of any particular MIP can be determined by analysis of the interactions between the cross-linker and template. This could be done either virtually using computational modelling or by template adsorption using a small library of polymers prepared using different cross-linkers.

Rational Thinking in School-Based Practice

Science.gov (United States)

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…

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

Science.gov (United States)

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.

Ventilation, good indoor air quality and rational use of energy

DEFF Research Database (Denmark)

Clausen, Geo; Fernandes, E. D. O.; DeGids, W.

2003-01-01

The aim of this report is to provide information and advice to policy and decission makers, researchers, architects, designers, and manufacturers on strategies for achieving a good balance between good indoor air quality (IAQ) and the rational use of Energy in buildings, available guidelines...

Updated Army Cook Staffing Model to Reflect Workloads Generated by Current Field Feeding Operations, Group Rations, and Kitchens

National Research Council Canada - National Science Library

Kirejczyk, Harry J

2006-01-01

...: the Unitized Group Ration-A (UGR-A) and the Unitized Group Ration-Heat/Serve (UGR-H/S). These fieldings were designed to increase the frequency and quality of group hot meals and reduce the cook workloads generated by field feeding operations...

Dielectronic recombination of highly ionized iron

International Nuclear Information System (INIS)

Griffin, D.C.; Pindzola, M.S.

1987-01-01

Dielectronic recombination of the iron ions Fe/sup 15+/, Fe/sup 23+/, and Fe/sup 25+/ has been studied in the isolated-resonance, distorted-wave approximation. The cross-section calculations include the dielec- tronic transitions associated with the 3s→3l and 3s→4l excitations in Fe/sup 15+/, the 2s→2p and 2s→3l excitations in Fe/sup 23+/, and the 1s→2l excitations in Fe/sup 25+/. The effects of external electric fields have been included by employing intermediate-coupled, field-mixed eigenvectors for the doubly excited Rydberg states, determined by diagonalizing a Hamiltonian matrix which includes the internal electrostatic and spin-orbit terms, as well as the Stark matrix elements. The field effects are found to be quite large in Fe/sup 15+/, relatively small in Fe/sup 23+/, and negligible in Fe/sup 25+/. The calculations indicate that there are large resonances near threshold in Fe/sup 23+/ that are unaffected by external fields and may be measurable in new experiments currently being designed. In addition, the contributions of radiative recombination and the possible interference between radiative and dielectronic recombination in low-lying resonances are considered. Even though the radiative recombination cross sections may be appreciable near threshold in Fe/sup 15+/ and Fe/sup 23+/, the interference between these processes appears to be completely negligible

Rationality in Machiavelli and in Kant

Directory of Open Access Journals (Sweden)

Vadim Chaly

2016-11-01

Full Text Available The paper contains interpretation and comparative analysis of Machiavelli’s and Kant’s conceptions on rationality as two prime examples of “realist” and “idealist” modes of agency. Kantian model of rationality is viewed as an augmentation of the Machiavellian one, not an opposition to it. To elaborate the point, Robert Aumann’s model of act-rationality and rulerationality is applied to the two philosophical models. Kantian practical reason is interpreted as an addition to Aumann’s instrumental rationality, providing rules for rules, or “rule-rule-rationality”.

Towards a Rational Kingdom in Africa: Knowledge, Critical Rationality and Development in a Twenty-First Century African Cultural Context

Directory of Open Access Journals (Sweden)

Lawrence Ogbo Ugwuanyi

2018-03-01

Full Text Available This paper seeks to locate the kind of knowledge that is relevant for African development in the twenty-first century African cultural context and to propose the paradigm for achieving such knowledge. To do this, it advances the view that the concept of twenty-first century in an African context must be located with the colonial and post-colonial challenges of the African world and applied to serve the African demand. Anchored on this position, the paper outlines and critiques the wrong assumption on which modern state project was anchored in post-colonial Africa and its development dividend to suggest that this is an outcome of a wrong knowledge design that is foundational to the state project and which the project did not address. It proposes a shift in the knowledge paradigm in Africa and suggests critical self-consciousness as a more desirable knowledge design for Africa. It applies the term ‘rational kingdom’ (defined as a community of reason marked by critical conceptual self-awareness driven by innovation and constructivism to suggest this paradigm. ‘Innovation’ is meant as the application of reason with an enlarged capacity to anticipate and address problems with fresh options and ‘constructivism’ is meant as the disposition to sustain innovation by advancing an alternative but more reliable worldview that can meet the exigencies of modernity in an African cultural context. The paper then proceeds to outline the nature of the rational kingdom and its anticipated gains and outcomes. It applies the method of inductive reasoning to advance its position. To do this it invokes selected but crucial areas of African life to locate how the developmental demands of these aspects of life suggest a critical turn in African rationality.

A therapeutic HIV vaccine using coxsackie-HIV recombinants: a possible new strategy.

Science.gov (United States)

Halim, S S; Collins, D N; Ramsingh, A I

2000-10-10

The ultimate goal in the treatment of HIV-infected persons is to prevent disease progression. A strategy to accomplish this goal is to use chemotherapy to reduce viral load followed by immunotherapy to stimulate HIV-specific immune responses that are observed in long-term asymptomatic individuals. An effective, live, recombinant virus, expressing HIV sequences, would be capable of inducing both CTL and CD4(+) helper T cell responses. To accomplish these goals, the viral vector must be immunogenic yet retain its avirulent phenotype in a T cell-deficient host. We have identified a coxsackievirus variant, CB4-P, that can induce protective immunity against a virulent variant. In addition, the CB4-P variant remains avirulent in mice lacking CD4(+) helper T cells, suggesting that CB4-P may be uniquely suited as a viral vector for a therapeutic HIV vaccine. Two strategies designed to elicit CTL and CD4(+) helper T cell responses were used to construct CB4-P/HIV recombinants. Recombinant viruses were viable, genetically stable, and retained the avirulent phenotype of the parental virus. In designing a viral vector for vaccine development, an issue that must be addressed is whether preexisting immunity to the vector would affect subsequent administration of the recombinant virus. Using a test recombinant, we showed that prior exposure to the parental CB4-P virus did not affect the ability of the recombinant to induce a CD4(+) T cell response against the foreign sequence. The results suggest that a "cocktail" of coxsackie/HIV recombinants may be useful as a therapeutic HIV vaccine.

Rational Modular RNA Engineering Based on In Vivo Profiling of Structural Accessibility.

Science.gov (United States)

Leistra, Abigail N; Amador, Paul; Buvanendiran, Aishwarya; Moon-Walker, Alex; Contreras, Lydia M

2017-12-15

Bacterial small RNAs (sRNAs) have been established as powerful parts for controlling gene expression. However, development and application of engineered sRNAs has primarily focused on regulating novel synthetic targets. In this work, we demonstrate a rational modular RNA engineering approach that uses in vivo structural accessibility measurements to tune the regulatory activity of a multisubstrate sRNA for differential control of its native target network. Employing the CsrB global sRNA regulator as a model system, we use published in vivo structural accessibility data to infer the contribution of its local structures (substructures) to function and select a subset for engineering. We then modularly recombine the selected substructures, differentially representing those of presumed high or low functional contribution, to build a library of 21 CsrB variants. Using fluorescent translational reporter assays, we demonstrate that the CsrB variants achieve a 5-fold gradient of control of well-characterized Csr network targets. Interestingly, results suggest that less conserved local structures within long, multisubstrate sRNAs may represent better targets for rational engineering than their well-conserved counterparts. Lastly, mapping the impact of sRNA variants on a signature Csr network phenotype indicates the potential of this approach for tuning the activity of global sRNA regulators in the context of metabolic engineering applications.

Effective Entrepreneurial Choice: The Role of Rationality and Non-Rationality in Three Entrepreneurs Success Stories

OpenAIRE

Chong, Anne Michele, Siang Yoon

2007-01-01

Good entrepreneurship is important for economic growth and productivity in any modern economy. The purpose of this dissertation is to research how good entrepreneurial decisions are made. In theory, optimal or rational decision making means choosing the best alternative in response to the problem. However, in reality, people do not act rationally because they often cannot make rational choices. The reason is that people do not have enough brain power, time or resources to process the compl...

Genetic Characterization of a Novel HIV-1 Circulating Recombinant Form (CRF74_01B) Identified among Intravenous Drug Users in Malaysia: Recombination History and Phylogenetic Linkage with Previously Defined Recombinant Lineages.

Science.gov (United States)

Cheong, Hui Ting; Chow, Wei Zhen; Takebe, Yutaka; Chook, Jack Bee; Chan, Kok Gan; Al-Darraji, Haider Abdulrazzaq Abed; Koh, Clayton; Kamarulzaman, Adeeba; Tee, Kok Keng

2015-01-01

In many parts of Southeast Asia, the HIV-1 epidemic has been driven by the sharing of needles and equipment among intravenous drug users (IDUs). Over the last few decades, many studies have proven time and again that the diversity of HIV-1 epidemics can often be linked to the route of infection transmission. That said, the diversity and complexity of HIV-1 molecular epidemics in the region have been increasing at an alarming rate, due in part to the high tendency of the viral RNA to recombine. This scenario was exemplified by the discovery of numerous circulating recombinant forms (CRFs), especially in Thailand and Malaysia. In this study, we characterized a novel CRF designated CRF74_01B, which was identified in six epidemiologically unlinked IDUs in Kuala Lumpur, Malaysia. The near-full length genomes were composed of CRF01_AE and subtype B', with eight breakpoints dispersed in the gag-pol and nef regions. Remarkably, this CRF shared four and two recombination hotspots with the previously described CRF33_01B and the less prevalent CRF53_01B, respectively. Genealogy-based Bayesian phylogenetic analysis of CRF74_01B genomic regions showed that it is closely related to both CRF33_01B and CRF53_01B. This observation suggests that CRF74_01B was probably a direct descendent from specific lineages of CRF33_01B, CRF53_01B and subtype B' that could have emerged in the mid-1990s. Additionally, it illustrated the active recombination processes between prevalent HIV-1 subtypes and recombinants in Malaysia. In summary, we report a novel HIV-1 genotype designated CRF74_01B among IDUs in Kuala Lumpur, Malaysia. The characterization of the novel CRF74_01B is of considerable significance towards the understanding of the genetic diversity and population dynamics of HIV-1 circulating in the region.

Genetic Characterization of a Novel HIV-1 Circulating Recombinant Form (CRF74_01B Identified among Intravenous Drug Users in Malaysia: Recombination History and Phylogenetic Linkage with Previously Defined Recombinant Lineages.

Directory of Open Access Journals (Sweden)

Hui Ting Cheong

Full Text Available In many parts of Southeast Asia, the HIV-1 epidemic has been driven by the sharing of needles and equipment among intravenous drug users (IDUs. Over the last few decades, many studies have proven time and again that the diversity of HIV-1 epidemics can often be linked to the route of infection transmission. That said, the diversity and complexity of HIV-1 molecular epidemics in the region have been increasing at an alarming rate, due in part to the high tendency of the viral RNA to recombine. This scenario was exemplified by the discovery of numerous circulating recombinant forms (CRFs, especially in Thailand and Malaysia. In this study, we characterized a novel CRF designated CRF74_01B, which was identified in six epidemiologically unlinked IDUs in Kuala Lumpur, Malaysia. The near-full length genomes were composed of CRF01_AE and subtype B', with eight breakpoints dispersed in the gag-pol and nef regions. Remarkably, this CRF shared four and two recombination hotspots with the previously described CRF33_01B and the less prevalent CRF53_01B, respectively. Genealogy-based Bayesian phylogenetic analysis of CRF74_01B genomic regions showed that it is closely related to both CRF33_01B and CRF53_01B. This observation suggests that CRF74_01B was probably a direct descendent from specific lineages of CRF33_01B, CRF53_01B and subtype B' that could have emerged in the mid-1990s. Additionally, it illustrated the active recombination processes between prevalent HIV-1 subtypes and recombinants in Malaysia. In summary, we report a novel HIV-1 genotype designated CRF74_01B among IDUs in Kuala Lumpur, Malaysia. The characterization of the novel CRF74_01B is of considerable significance towards the understanding of the genetic diversity and population dynamics of HIV-1 circulating in the region.

Rationalization and Design of Enhanced Photoinduced Cycloreversion in Photochromic Dimethyldihydropyrenes by Theoretical Calculations.

Science.gov (United States)

Boggio-Pasqua, Martial; Garavelli, Marco

2015-06-11

This study presents a computational investigation of the initial step of the dimethyldihydropyrene (DHP) to cyclophanediene (CPD) photoinduced ring-opening reaction using time-dependent density functional theory (TD-DFT). In particular, the photochemical path corresponding to the formation of the CPD precursor (CPD*) on the zwitterionic state is scrutinized. The TD-DFT approach was first validated on the parent compound against accurate ab initio calculations. It confirms that CPD* formation is efficiently quenched in this system by an easily accessible S2/S1 conical intersection located in the vicinity of the CPD* minimum and leading to a locally excited state minimum responsible for DHP luminescence. Increased ring-opening quantum yields were observed in benzo[e]-fused-DHP (DHP-1), isobutenyl-DHP (DHP-2), and naphthoyl-DHP (DHP-3). The calculations show that CPD* formation is much more favorable in these systems, either due to an inversion of electronic states in DHP-1, suppressing the formation of the locally excited state, or due to efficient stabilization of CPD* on the S1 potential energy surface in DHP-2 and DHP-3. Both effects can be combined in a rationally designed benzo[e]-fused-naphthoyl-DHP (DHP-4) for which we anticipate an unprecedented efficiency.

Accelerated and Rational Design of Improved CHO Cell Factories

DEFF Research Database (Denmark)

Grav, Lise Marie

Recombinant production of therapeutic proteins provides huge benefits to human health and promises solutions to some of the most devastating and currently untreatable diseases in healthcare. Key to the development of new therapeutic proteins is to optimize and engineer living cells, namely cell...... of a number of novel tools is reported that aim to accelerate the construction of production cell lines for therapeutic proteins with optimal phenotypic attributes for industrial processes. Chinese hamster ovary (CHO) cells are the predominant production host for therapeutic proteins, and are the cell factory...... of interest in this thesis. The core of the thesis is revolved around the development and application of genome editing techniques that enable us to precisely engineer the genome of CHO cells by either rendering specific-targeted genes unfunctional or inserting new genes in precise genomic locations...

Changing fields of rationality - a policy for change?

Energy Technology Data Exchange (ETDEWEB)

Strumse, Einar; Westskog, Hege; Winther, Tanja

2010-07-01

Work objective: To analyze effective strategies for changing households' energy consumption based on an interdisciplinary model for understanding change. Methodology: In this paper we develop a conceptual model for understanding individuals' energy consumption. We synthesize insights from anthropology, social psychology and economics grasping perspectives from behaviour to practice and from the Bourdieu's fields to rationality thinking in economics. We use this insight to analyze strategies for change. Abstract: In this paper we analyze effective strategies for changing households' energy consumption based on an interdisciplinary model for understanding change. The model focuses on four main categories for understanding individual consumption: a. Material constraints b. Values and identity c. Norms d. Ability These are the main influencing factors of the individual's consumption level, but in interaction with the corresponding group and the societal levels for the same factors. The model can be illustrated. One combination of factors on all levels constitutes a field of rationality. We claim that an important strategy for changing energy consumption towards sustainability is changing the field of rationality of the individual. Changing of rationality fields would from our point of view initiate reflection which is an important condition for changed behavior. One example of changing of fields is information measures that relates energy consumption to the 'citizen' field rather than the 'consumer' field. Hence, according to our conceptual framework - how policy should be framed (information measures for instance ) would be an important knowledge area for design of effective policy measures. (Author)

Discrete Choice and Rational Inattention

DEFF Research Database (Denmark)

Fosgerau, Mogens; Melo, Emerson; de Palma, André

2017-01-01

This paper establishes a general equivalence between discrete choice and rational inattention models. Matejka and McKay (2015, AER) showed that when information costs are modelled using the Shannon entropy, the result- ing choice probabilities in the rational inattention model take the multinomial...... logit form. We show that when information costs are modelled using a class of generalized entropies, then the choice probabilities in any rational inattention model are observationally equivalent to some additive random utility discrete choice model and vice versa. This equivalence arises from convex...

Rational top and its classical r-matrix

International Nuclear Information System (INIS)

Aminov, G; Arthamonov, S; Smirnov, A; Zotov, A

2014-01-01

We construct a rational integrable system (the rational top) on a co-adjoint orbit of SL N Lie group. It is described by the Lax operator with spectral parameter and classical non-dynamical skew-symmetric r-matrix. In the case of the orbit of minimal dimension the model is gauge equivalent to the rational Calogero–Moser (CM) system. To obtain the results we represent the Lax operator of the CM model in two different factorized forms—without spectral parameter (related to the spinless case) and another one with the spectral parameter. The latter gives rise to the rational top while the first one is related to generalized Cremmer–Gervais r-matrices. The gauge transformation relating the rational top and CM model provides the classical rational version of the IRF-Vertex correspondence. From the geometrical point of view it describes the modification of SL(N,C)-bundles over degenerated elliptic curve. In view of the Symplectic Hecke Correspondence the rational top is related to the rational spin CM model. Possible applications and generalizations of the suggested construction are discussed. In particular, the obtained r-matrix defines a class of KZB equations. (paper)

Fiber sources for complete calf starter rations.

Science.gov (United States)

Murdock, F R; Wallenius, R W

1980-11-01

Complete calf starter rations containing either 1) alfalfa hay, 2) cottonseed hulls, or 3) alfalfa-beet pulp as sources of fiber were fed to Holstein heifer calves at two locations on a limited milk program from 3 days to 12 wk of age. Rations were isonitrogenous and similar in content of crude fiber and acid detergent fiber. Although growth and development were normal on all rations, calves fed the cottonseed hull ration consumed more starter and gained more body weight than calves fed the other sources of fiber. The similarity of feed efficiencies, rumen pH, and molar ratios of volatile fatty acids between rations indicated no appreciable differences in rumen development or function. The growth response of calves fed the cottonseed hull ration appeared to be a result of better ration acceptability for which no reason was evident. Calves raised at Puyallup gained more body weight than calves at Pullman, and these gains were made more efficiently. These location effects may be related to seasonal differences and greater demands for production of body heat. Although the incidence of scours was less for calves fed alfalfa hay starter, the incidence and severity of bloat were higher for that ration.

Lessons from Learning to Have Rational Expectations

OpenAIRE

Lindh, Thomas

1989-01-01

This paper reviews a growing literature investigating how economic agents may learn rational expectations. Fully rational learning requires implausible initial information assumptions, therefore some form of bounded rationality has come into focus. Such learning models often converge to rational expectations equilibria within certain bounds. Convergence analysis has been much simplified by methods from adaptive control theory. Learning stability as a correspondence principle show some promise...

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Suppressing recombination in polymer photovoltaic devices via energy-level cascades.

Science.gov (United States)

Tan, Zhi-Kuang; Johnson, Kerr; Vaynzof, Yana; Bakulin, Artem A; Chua, Lay-Lay; Ho, Peter K H; Friend, Richard H

2013-08-14

An energy cascading structure is designed in a polymer photovoltaic device to suppress recombination and improve quantum yields. By the insertion of a thin polymer interlayer with intermediate energy levels, electrons and holes can effectively shuttle away from each other while being spatially separated from recombination. An increase in open-circuit voltage and short-circuit current are observed in modified devices. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Strategy selection as rational metareasoning.

Science.gov (United States)

Lieder, Falk; Griffiths, Thomas L

2017-11-01

Many contemporary accounts of human reasoning assume that the mind is equipped with multiple heuristics that could be deployed to perform a given task. This raises the question of how the mind determines when to use which heuristic. To answer this question, we developed a rational model of strategy selection, based on the theory of rational metareasoning developed in the artificial intelligence literature. According to our model people learn to efficiently choose the strategy with the best cost-benefit tradeoff by learning a predictive model of each strategy's performance. We found that our model can provide a unifying explanation for classic findings from domains ranging from decision-making to arithmetic by capturing the variability of people's strategy choices, their dependence on task and context, and their development over time. Systematic model comparisons supported our theory, and 4 new experiments confirmed its distinctive predictions. Our findings suggest that people gradually learn to make increasingly more rational use of fallible heuristics. This perspective reconciles the 2 poles of the debate about human rationality by integrating heuristics and biases with learning and rationality. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Should informed consent be based on rational beliefs?

Science.gov (United States)

Savulescu, J; Momeyer, R W

1997-10-01

Our aim is to expand the regulative ideal governing consent. We argue that consent should not only be informed but also based on rational beliefs. We argue that holding true beliefs promotes autonomy. Information is important insofar as it helps a person to hold the relevant true beliefs. But in order to hold the relevant true beliefs, competent people must also think rationally. Insofar as information is important, rational deliberation is important. Just as physicians should aim to provide relevant information regarding the medical procedures prior to patients consenting to have those procedures, they should also assist patients to think more rationally. We distinguish between rational choice/action and rational belief. While autonomous choice need not necessarily be rational, it should be based on rational belief. The implication for the doctrine of informed consent and the practice of medicine is that, if physicians are to respect patient autonomy and help patients to choose and act more rationally, not only must they provide information, but they should care more about the theoretical rationality of their patients. They should not abandon their patients to irrationality. They should help their patients to deliberate more effectively and to care more about thinking rationally. We illustrate these arguments in the context of Jehovah's Witnesses refusing life-saving blood transfusions. Insofar as Jehovah's Witnesses should be informed of the consequences of their actions, they should also deliberate rationally about these consequences.

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

Science.gov (United States)

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.

Rational optimization of reliability and safety policies

International Nuclear Information System (INIS)

Melchers, Robert E.

2001-01-01

Optimization of structures for design has a long history, including optimization using numerical methods and optimality criteria. Much of this work has considered a subset of the complete design optimization problem--that of the technical issues alone. The more general problem must consider also non-technical issues and, importantly, the interplay between them and the parameters which influence them. Optimization involves optimal setting of design or acceptance criteria and, separately, optimal design within the criteria. In the modern context of probability based design codes this requires probabilistic acceptance criteria. The determination of such criteria involves more than the nominal code failure probability approach used for design code formulation. A more general view must be taken and a clear distinction must be made between those matters covered by technical reliability and non-technical reliability. The present paper considers this issue and outlines a framework for rational optimization of structural and other systems given the socio-economic and political systems within which optimization must be performed

Evidence for natural recombination between mink enteritis virus and canine parvovirus

Directory of Open Access Journals (Sweden)

Wang Jianke

2012-10-01

Full Text Available Abstract A virus was isolated from mink showing clinical and pathological signs of enteritis in China. This virus, designated MEV/LN-10, was identified as mink enteritis virus (MEV based on its cytopathic effect in the feline F81 cell line, the hemagglutination (HA and hemagglutination inhibition (HI assay, electron microscopy (EM and animal infection experiments. The complete viral genome was cloned and sequenced. Phylogenetic and recombination analyses on the complete MEV/LN-10 genome showed evidence of recombination between MEV and canine parvovirus (CPV. The genome was composed of the NS1 gene originating from CPV while the VP1 gene was of MEV origin. This is the first demonstration of recombination between a CPV and MEV in nature. Our findings not only provide valuable evidence indicating that recombination is an important genetic mechanism contributing to the variation and evolution of MEV, but also that heterogeneous recombination can occur in the feline parvovirus subspecies.

Product differentiation under bounded rationality

NARCIS (Netherlands)

Vermeulen, B.; Poutré, La J.A.; Kok, de A.G.; Pyka, A.; Handa, H.; Ishibuchi, H.; Ong, Y.-S.; Tan, K.-C.

2015-01-01

We study product differentiation equilibria and dynamics on the Salop circle under bounded rationality. Due to bounded rationality, firms tend to agglomerate in pairs. Upon adding a second tier of component suppliers, downstream assemblers may escape pairwise horizontal agglomeration. Moreover, we

On the choice of a rational system of water economy of the industrial enterprice

International Nuclear Information System (INIS)

Tsikhelashvili, Z.; Khatiuri, Kh.; Verulava, G.; Zakutashvili, G.

2009-01-01

Rational systems and projects of water economy of the industrial enterprise (allowing for the development of waste-free production processes, industrial water recycling with water treatment or without it, and cooling recycling) are discussed. The analysis of rational systems is of primary importance when designing and/or reconstructing the industrial water economy. Such systems and projects must account for all local conditions determining the advantage of their employment from the sanitary and economic viewpoints. (author)

An evaluation of rational-emotive imagery as a component of rational-emotive therapy in the treatment of test anxiety.

Science.gov (United States)

Hymen, S P; Warren, R

1978-06-01

This study evaluated the efficacy of rational-emotive imagery as a component of rational-emotive therapy in reduction of college students' test anxiety. 11 volunteers met for 6 1-hr. group treatment sessions over a 3-wk. period. After 2 initial treatment sessions subjects were randomly assigned to groups given either rational-emotive therapy with rational-emotive imagery or rational-emotive therapy without imagery. Contrary to predictions, improvement between groups on self-report and performance measures was nonsignificant. Failure to obtain differences was attributed to similarities in content of treatment sessions and short treatment time. Combined groups reported significant improvement on all dependent measures. Although the study did not yield the predicted benefits of the imagery, results lend further support to the efficacy of rational-emotive therapy procedures in the reduction of test anxiety.

Polymer:Nonfullerene Bulk Heterojunction Solar Cells with Exceptionally Low Recombination Rates

KAUST Repository

Gasparini, Nicola; Salvador, Michael; Heumueller, Thomas; Richter, Moses; Classen, Andrej; Shrestha, Shreetu; Matt, Gebhard J.; Holliday, Sarah; Strohm, Sebastian; Egelhaaf, Hans-Joachim; Wadsworth, Andrew; Baran, Derya; McCulloch, Iain; Brabec, Christoph J.

2017-01-01

Organic semiconductors are in general known to have an inherently lower charge carrier mobility compared to their inorganic counterparts. Bimolecular recombination of holes and electrons is an important loss mechanism and can often be described by the Langevin recombination model. Here, the device physics of bulk heterojunction solar cells based on a nonfullerene acceptor (IDTBR) in combination with poly(3-hexylthiophene) (P3HT) are elucidated, showing an unprecedentedly low bimolecular recombination rate. The high fill factor observed (above 65%) is attributed to non-Langevin behavior with a Langevin prefactor (β/βL) of 1.9 × 10−4. The absence of parasitic recombination and high charge carrier lifetimes in P3HT:IDTBR solar cells inform an almost ideal bimolecular recombination behavior. This exceptional recombination behavior is explored to fabricate devices with layer thicknesses up to 450 nm without significant performance losses. The determination of the photoexcited carrier mobility by time-of-flight measurements reveals a long-lived and nonthermalized carrier transport as the origin for the exceptional transport physics. The crystalline microstructure arrangement of both components is suggested to be decisive for this slow recombination dynamics. Further, the thickness-independent power conversion efficiency is of utmost technological relevance for upscaling production and reiterates the importance of understanding material design in the context of low bimolecular recombination.

Polymer:Nonfullerene Bulk Heterojunction Solar Cells with Exceptionally Low Recombination Rates

KAUST Repository

Gasparini, Nicola

2017-09-01

Organic semiconductors are in general known to have an inherently lower charge carrier mobility compared to their inorganic counterparts. Bimolecular recombination of holes and electrons is an important loss mechanism and can often be described by the Langevin recombination model. Here, the device physics of bulk heterojunction solar cells based on a nonfullerene acceptor (IDTBR) in combination with poly(3-hexylthiophene) (P3HT) are elucidated, showing an unprecedentedly low bimolecular recombination rate. The high fill factor observed (above 65%) is attributed to non-Langevin behavior with a Langevin prefactor (β/βL) of 1.9 × 10−4. The absence of parasitic recombination and high charge carrier lifetimes in P3HT:IDTBR solar cells inform an almost ideal bimolecular recombination behavior. This exceptional recombination behavior is explored to fabricate devices with layer thicknesses up to 450 nm without significant performance losses. The determination of the photoexcited carrier mobility by time-of-flight measurements reveals a long-lived and nonthermalized carrier transport as the origin for the exceptional transport physics. The crystalline microstructure arrangement of both components is suggested to be decisive for this slow recombination dynamics. Further, the thickness-independent power conversion efficiency is of utmost technological relevance for upscaling production and reiterates the importance of understanding material design in the context of low bimolecular recombination.

Rationing in health systems: A critical review.

Science.gov (United States)

Keliddar, Iman; Mosadeghrad, Ali Mohammad; Jafari-Sirizi, Mehdi

2017-01-01

Background: It is difficult to provide health care services to all those in need of such services due to limited resources and unlimited demands. Thus, priority setting and rationing have to be applied. This study aimed at critically examining the concept of rationing in health sector and identifying its purposes, influencing factors, mechanisms, and outcomes. Methods: The critical interpretive synthesis methodology was used in this study. PubMed, Cochrane, and Proquest databases were searched using the related key words to find related documents published between 1970 and 2015. In total, 161 published reports were reviewed and included in the study. Thematic content analysis was applied for data analysis. Results: Health services rationing means restricting the access of some people to useful or potentially useful health services due to budgetary limitation. The inherent features of the health market and health services, limited resources, and unlimited needs necessitate health services rationing. Rationing can be applied in 4 levels: health care policy- makers, health care managers, health care providers, and patients. Health care rationing can be accomplished through fixed budget, benefit package, payment mechanisms, queuing, copayments, and deductibles. Conclusion: This paper enriched our understanding of health services rationing and its mechanisms at various levels and contributed to the literature by broadly conceptualizing health services rationing.

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

Science.gov (United States)

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

2014-01-01

In nature, proteins play a significant role in biomineral formation. One of the ultimate goals of bioinspired materials science is to develop highly stable synthetic molecules that mimic the function of these natural proteins by controlling crystal formation. Here, we demonstrate that both the morphology and the degree of acceleration or inhibition observed during growth of calcite in the presence of peptoids can be rationally tuned by balancing the electrostatic and hydrophobic interactions, with hydrophobic interactions playing the dominant role. While either strong electrostatic or hydrophobic interactions inhibit growth and reduces expression of the {104} faces, correlations between peptoid-crystal binding energies and observed changes in calcite growth indicate moderate electrostatic interactions allow peptoids to weakly adsorb while moderate hydrophobic interactions cause disruption of surface-adsorbed water layers, leading to growth acceleration with retained expression of the {104} faces. This study provides fundamental principles for designing peptoids as crystallization promoters, and offers a straightforward screening method based on macroscopic crystal morphology. Because peptoids are sequence-specific, highly stable, and easily synthesized, peptoid-enhanced crystallization offers a broad range of potential applications. PMID:25189418

Rational Design of Zirconium-doped Titania Photocatalysts with Synergistic Brønsted Acidity and Photoactivity.

Science.gov (United States)

Ma, Runyuan; Wang, Liang; Zhang, Bingsen; Yi, Xianfeng; Zheng, Anmin; Deng, Feng; Yan, Xuhua; Pan, Shuxiang; Wei, Xiao; Wang, Kai-Xue; Su, Dang Sheng; Xiao, Feng-Shou

2016-10-06

The preparation of photocatalysts with high activities under visible-light illumination is challenging. We report the rational design and construction of a zirconium-doped anatase catalyst (S-Zr-TiO 2 ) with Brønsted acidity and photoactivity as an efficient catalyst for the degradation of phenol under visible light. Electron microscopy images demonstrate that the zirconium sites are uniformly distributed on the sub-10 nm anatase crystals. UV-visible spectrometry indicates that the S-Zr-TiO 2 is a visible-light-responsive catalyst with narrower band gap than conventional anatase. Pyridine-adsorption infrared and acetone-adsorption 13 C NMR spectra confirm the presence of Brønsted acidic sites on the S-Zr-TiO 2 sample. Interestingly, the S-Zr-TiO 2 catalyst exhibits high catalytic activity in the degradation of phenol under visible-light illumination, owing to a synergistic effect of the Brønsted acidity and photoactivity. Importantly, the S-Zr-TiO 2 shows good recyclability. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rationally Designed, Multifunctional Self-Assembled Nanoparticles for Covalently Networked, Flexible and Self-Healable Superhydrophobic Composite Films.

Science.gov (United States)

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

2018-03-21

For constructing bioinspired functional films with various superhydrophobic functions, including self-cleaning, anticorrosion, antibioadhesion, and oil-water separation, hydrophobic nanomaterials have been widely used as crucial structural components. In general, hydrophobic nanomaterials, however, cannot form strong chemical bond networks in organic-inorganic hybrid composite films because of the absence of chemically compatible binding components. Herein, we report the rationally designed, multifunctional self-assembled nanoparticles with tunable functionalities of covalent cross-linking and hydrophobicity for constructing three-dimensionally interconnected superhydrophobic composite films via a facile solution-based fabrication at room temperature. The multifunctional self-assembled nanoparticles allow the systematic control of functionalities of composite films, as well as the stable formation of covalently linked superhydrophobic composite films with excellent flexibility (bending radii of 6.5 and 3.0 mm, 1000 cycles) and self-healing ability (water contact angle > 150°, ≥10 cycles). The presented strategy can be a versatile and effective route to generating other advanced functional films with covalently interconnected composite networks.

CSReport: A New Computational Tool Designed for Automatic Analysis of Class Switch Recombination Junctions Sequenced by High-Throughput Sequencing.

Science.gov (United States)

Boyer, François; Boutouil, Hend; Dalloul, Iman; Dalloul, Zeinab; Cook-Moreau, Jeanne; Aldigier, Jean-Claude; Carrion, Claire; Herve, Bastien; Scaon, Erwan; Cogné, Michel; Péron, Sophie

2017-05-15

B cells ensure humoral immune responses due to the production of Ag-specific memory B cells and Ab-secreting plasma cells. In secondary lymphoid organs, Ag-driven B cell activation induces terminal maturation and Ig isotype class switch (class switch recombination [CSR]). CSR creates a virtually unique IgH locus in every B cell clone by intrachromosomal recombination between two switch (S) regions upstream of each C region gene. Amount and structural features of CSR junctions reveal valuable information about the CSR mechanism, and analysis of CSR junctions is useful in basic and clinical research studies of B cell functions. To provide an automated tool able to analyze large data sets of CSR junction sequences produced by high-throughput sequencing (HTS), we designed CSReport, a software program dedicated to support analysis of CSR recombination junctions sequenced with a HTS-based protocol (Ion Torrent technology). CSReport was assessed using simulated data sets of CSR junctions and then used for analysis of Sμ-Sα and Sμ-Sγ1 junctions from CH12F3 cells and primary murine B cells, respectively. CSReport identifies junction segment breakpoints on reference sequences and junction structure (blunt-ended junctions or junctions with insertions or microhomology). Besides the ability to analyze unprecedentedly large libraries of junction sequences, CSReport will provide a unified framework for CSR junction studies. Our results show that CSReport is an accurate tool for analysis of sequences from our HTS-based protocol for CSR junctions, thereby facilitating and accelerating their study. Copyright © 2017 by The American Association of Immunologists, Inc.

Modelling of the operational behaviour of passive autocatalytic recombiners

International Nuclear Information System (INIS)

Schwarz, Ulrich

2011-01-01

Due to severe accidents in nuclear power plants, a significant amount of hydrogen can be produced. In pressurized water reactors, a possible and wide-spread measurement is the use of auto-catalytic recombiners. There are numerous numerical models describing the operational behaviour of recombiners for containment codes. The numerical model REKO-DIREKT was developed at the Forschungszentrum Juelich. This model describes the chemical reaction on the catalytic sheets by a physical model, as opposed to the usual codes based on empirical correlations. Additionally, there have been experimental studies concerning the catalytic recombination of hydrogen since the 1990s. The aim of this work is the further development of the program REKO-DIREKT to an independent recombiner model for severe accident and containment codes. Therefore, the catalyst model already existed has been submitted by a parameter optimization with an experimental database expanded during this work. In addition, a chimney model has been implemented which allows the calculation of the free convection flow through the recombiner housing due to the exothermal reaction. This model has been tested by experimental data gained by a recently built test facility. The complete recombiner model REKO-DIREKT has been validated by data from literature. Another aim of this work is the derivation of the reaction kinetics for recombiner designs regarding future reactor concepts. Therefore, experimental studies both on single catalytic coated meshes as well as on two meshes installed in a row have been performed in laboratory scale. By means of the measured data, a theoretical approach for the determination of the reaction rate has been derived.

Research on Bounded Rationality of Fuzzy Choice Functions

Directory of Open Access Journals (Sweden)

Xinlin Wu

2014-01-01

Full Text Available The rationality of a fuzzy choice function is a hot research topic in the study of fuzzy choice functions. In this paper, two common fuzzy sets are studied and analyzed in the framework of the Banerjee choice function. The complete rationality and bounded rationality of fuzzy choice functions are defined based on the two fuzzy sets. An assumption is presented to study the fuzzy choice function, and especially the fuzzy choice function with bounded rationality is studied combined with some rationality conditions. Results show that the fuzzy choice function with bounded rationality also satisfies some important rationality conditions, but not vice versa. The research gives supplements to the investigation in the framework of the Banerjee choice function.

The use of protein structure/activity relationships in the rational design of stable particulate delivery systems

Directory of Open Access Journals (Sweden)

M.H.B. Costa

2002-06-01

Full Text Available The recombinant heat shock protein (18 kDa-hsp from Mycobacterium leprae was studied as a T-epitope model for vaccine development. We present a structural analysis of the stability of recombinant 18 kDa-hsp during different processing steps. Circular dichroism and ELISA were used to monitor protein structure after thermal stress, lyophilization and chemical modification. We observed that the 18 kDa-hsp is extremely resistant to a wide range of temperatures (60% of activity is retained at 80ºC for 20 min. N-Acylation increased its ordered structure by 4% and decreased its ß-T1 structure by 2%. ELISA demonstrated that the native conformation of the 18 kDa-hsp was preserved after hydrophobic modification by acylation. The recombinant 18 kDa-hsp resists to a wide range of temperatures and chemical modifications without loss of its main characteristic, which is to be a source of T epitopes. This resistance is probably directly related to its lack of organization at the level of tertiary and secondary structures.

Fundamental Investigations and Rational Design of Durable High-Performance SOFC Cathodes

Energy Technology Data Exchange (ETDEWEB)

Chen, Yu [Georgia Inst. of Technology, Atlanta, GA (United States); Ding, Dong [Georgia Inst. of Technology, Atlanta, GA (United States); Wei, Tao [Georgia Inst. of Technology, Atlanta, GA (United States); Liu, Meilin [Georgia Inst. of Technology, Atlanta, GA (United States)

2016-03-31

The main objective of this project is to unravel the degradation mechanism of LSCF cathodes under realistic operating conditions with different types of contaminants, aiming towards the rational design of cathodes with high-performance and enhanced durability by combining a porous backbone (such as LSCF) with a thin catalyst coating. The mechanistic understanding will help us to optimize the composition and morphology of the catalyst layer and microstructure of the LSCF backbone for better performance and durability. More specifically, the technical objectives include: (1) to unravel the degradation mechanism of LSCF cathodes under realistic operating conditions with different types of contaminants using in situ and ex situ measurements performed on specially-designed cathodes; (2) to examine the microstructural and compositional evolution of LSCF cathodes as well as the cathode/electrolyte interfaces under realistic operating conditions; (3) to correlate the fuel cell performance instability and degradation with the microstructural and morphological evolution and surface chemistry change of the cathode under realistic operating conditions; (4) to explore new catalyst materials and electrode structures to enhance the stability of the LSCF cathode under realistic operating conditions; and (5) to validate the long term stability of the modified LSCF cathode in commercially available cells under realistic operating conditions. We have systematically evaluated LSCF cathodes in symmetrical cells and anode supported cells under realistic conditions with different types of contaminants such as humidity, CO₂, and Cr. Electrochemical models for the design of test cells and understanding of mechanisms have been developed for the exploration of fundamental properties of electrode materials. It is demonstrated that the activity and stability of LSCF cathodes can be degraded by the introduction of contaminants. The microstructural and compositional evolution of LSCF

Rational risk-based decision support for drinking water well managers by optimized monitoring designs

Science.gov (United States)

Enzenhöfer, R.; Geiges, A.; Nowak, W.

2011-12-01

Advection-based well-head protection zones are commonly used to manage the contamination risk of drinking water wells. Considering the insufficient knowledge about hazards and transport properties within the catchment, current Water Safety Plans recommend that catchment managers and stakeholders know, control and monitor all possible hazards within the catchments and perform rational risk-based decisions. Our goal is to supply catchment managers with the required probabilistic risk information, and to generate tools that allow for optimal and rational allocation of resources between improved monitoring versus extended safety margins and risk mitigation measures. To support risk managers with the indispensable information, we address the epistemic uncertainty of advective-dispersive solute transport and well vulnerability (Enzenhoefer et al., 2011) within a stochastic simulation framework. Our framework can separate between uncertainty of contaminant location and actual dilution of peak concentrations by resolving heterogeneity with high-resolution Monte-Carlo simulation. To keep computational costs low, we solve the reverse temporal moment transport equation. Only in post-processing, we recover the time-dependent solute breakthrough curves and the deduced well vulnerability criteria from temporal moments by non-linear optimization. Our first step towards optimal risk management is optimal positioning of sampling locations and optimal choice of data types to reduce best the epistemic prediction uncertainty for well-head delineation, using the cross-bred Likelihood Uncertainty Estimator (CLUE, Leube et al., 2011) for optimal sampling design. Better monitoring leads to more reliable and realistic protection zones and thus helps catchment managers to better justify smaller, yet conservative safety margins. In order to allow an optimal choice in sampling strategies, we compare the trade-off in monitoring versus the delineation costs by accounting for ill

Parallel steady state studies on a milliliter scale accelerate fed-batch bioprocess design for recombinant protein production with Escherichia coli.

Science.gov (United States)

Schmideder, Andreas; Cremer, Johannes H; Weuster-Botz, Dirk

2016-11-01

In general, fed-batch processes are applied for recombinant protein production with Escherichia coli (E. coli). However, state of the art methods for identifying suitable reaction conditions suffer from severe drawbacks, i.e. direct transfer of process information from parallel batch studies is often defective and sequential fed-batch studies are time-consuming and cost-intensive. In this study, continuously operated stirred-tank reactors on a milliliter scale were applied to identify suitable reaction conditions for fed-batch processes. Isopropyl β-d-1-thiogalactopyranoside (IPTG) induction strategies were varied in parallel-operated stirred-tank bioreactors to study the effects on the continuous production of the recombinant protein photoactivatable mCherry (PAmCherry) with E. coli. Best-performing induction strategies were transferred from the continuous processes on a milliliter scale to liter scale fed-batch processes. Inducing recombinant protein expression by dynamically increasing the IPTG concentration to 100 µM led to an increase in the product concentration of 21% (8.4 g L -1 ) compared to an implemented high-performance production process with the most frequently applied induction strategy by a single addition of 1000 µM IPGT. Thus, identifying feasible reaction conditions for fed-batch processes in parallel continuous studies on a milliliter scale was shown to be a powerful, novel method to accelerate bioprocess design in a cost-reducing manner. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1426-1435, 2016. © 2016 American Institute of Chemical Engineers.

The Application of Rational-Emotive Behavior Therapy to Reduce Stress among Mother with Leukemia Children

Directory of Open Access Journals (Sweden)

Yuni Sufyanti Arief

2016-09-01

Full Text Available Introduction: A child who is diagnosed with Leukemia will undergo several procedures are long and painful action. During the process of hospitalization due to leukemia children and parents can experience a variety of events or actions handling according to various studies shown by the experience very traumatic and stressful (Supartini 2004 in Arif, SY, 2007. Some of the methods used to deal with anxiety is psikoprofilaksis, relaxation and imagination (Reeder et al., 2011. Rational-emotive behavior therapy by Albert Ellis in 1990 describes a unique man who is basically have a tendency to think rational and irrational. Methods: aim of this study is to explain the effect of Rational Emotive Behavior Therapy (REBT for stress levels of mothers with children suffering from Leukemia. The study design used was a pre-experiment Quasy-post control group design. The sample was 10 mothers of children diagnosed with leukemia are treated in a child hematology ward Soetomo hospital. Variable in this study is the level of depression and anxiety mothers with children suffering from leukemia. Result: Based on the results obtained Wilcoxon statistical test p = 0.025 in the treatment group and p = 0.32 in the control group. Mann Whitney test results obtained p = 0.012. Conclution: Rational-emotive behavior therapy can reduce levels of depression and anxiety (stress mothers with children suffering from leukemia. It is expected that the application of rational -emotive behavior therapy can be done to reduce depression and anxiety in women with chronic disease cases while maintaining the effectiveness the goal of REBT. Keywords: stress, anxiety, depression, rational-emotive behavior

Development of modified rational buyer auction for procurement of ancillary services utilizing participation matrix

International Nuclear Information System (INIS)

Jamalzadeh, R.; Ardehali, M.M.; Rashidinejad, M.

2008-01-01

The rational buyer auction is based on a simultaneous auction that is the redesigned auction mechanism for ancillary services by the California independent system operator (CAISO). The incentive for the rational buyer auction is CAISO's intent to adopt a common sense rule of substituting higher-quality lower-cost services for lower-quality higher-cost services, when it results in reduced total procurement cost. For the purposes of designing a desirable auction where the minimum cost for the objective function as well as prevention of price reversal are achieved, either the payment cost in marginal pricing auction must be lowered or price reversal in rational buyer auction must be avoided. The objectives of this study are (a) to develop a newly proposed 'modified rational buyer' auction that does not allow price reversal and (b) to propose and validate a solution procedure that is based on participation matrix and discrete programming. The validation of the proposed solution procedure is accomplished through examination of two case studies available in the literature. Based on the first case study data, it is shown that the newly developed modified rational buyer auction avoids price reversal occurrence, while the total payment of ISO is increased by 5.8%, as compared with rational buyer auction. Also in comparison with marginal pricing auction, the ISO payment is lowered by 38.8%, when the newly developed modified rational buyer auction is utilized. For future work, it is recommended that the application of the modified rational buyer auction to joint dispatch of energy and ancillary services is investigated

Using Rational-Emotive Therapy to Prevent Classroom Problems.

Science.gov (United States)

Webber, Jo; Coleman, Maggie

1988-01-01

Teachers are encouraged to utilize rational-emotive therapy to prevent and deal with classroom behavior problems. Rational-emotive therapy is defined, the ABC model of rational thinking briefly explained, types of irrational thinking identified, and suggestions for becoming a rational thinker are offered. Classroom examples are given. (DB)

[Rationalization, rationing, prioritization: terminology and ethical approaches to the allocation of limited resources in hematology/oncology].

Science.gov (United States)

Winkler, Eva

2011-01-01

The field of oncology with its numerous high-priced innovations contributes considerably to the fact that medical progress is expensive. Additionally, due to the demographic changes and the increasing life expectancy, a growing number of cancer patients want to profit from this progress. Since resources are limited also in the health system, the fair distribution of the available resources urgently needs to be addressed. Dealing with scarcity is a typical problem in the domain of justice theory; therefore, this article first discusses different strategies to manage limited resources: rationalization, rationing, and prioritization. It then presents substantive as well as procedural criteria that assist in the just distribution of effective health benefits. There are various strategies to reduce the utilization of limited resources: Rationalization means that efficiency reserves are being exhausted; by means of rationing, effective health benefits are withheld due to cost considerations. Rationing can occur implicitly and thus covertly, e.g. through budgeting or the implementation of waiting periods, or explicitly, through transparent rules or policies about healthcare coverage. Ranking medical treatments according to their importance (prioritization) is often a prerequisite for rationing decisions. In terms of requirements of justice, both procedural and substantive criteria (e.g. equality, urgency, benefit) are relevant for the acceptance and quality of a decision to limit access to effective health benefits. Copyright © 2011 S. Karger AG, Basel.

Rational design of improved pharmabiotics.

LENUS (Irish Health Repository)

Sleator, Roy D

2009-01-01

Herein we review the most recent advances in probiotic research and applications with particular emphasis on the novel concept of patho-biotechnology: the application of pathogen-derived (ex vivo and in vivo) stress survival strategies for the design of more technologically robust and effective probiotic cultures with improved biotechnological and clinical applications.

Recombining without Hotspots: A Comprehensive Evolutionary Portrait of Recombination in Two Closely Related Species of Drosophila

Science.gov (United States)

Smukowski Heil, Caiti S.; Ellison, Chris; Dubin, Matthew; Noor, Mohamed A.F.

2015-01-01

Meiotic recombination rate varies across the genome within and between individuals, populations, and species in virtually all taxa studied. In almost every species, this variation takes the form of discrete recombination hotspots, determined in some mammals by a protein called PRDM9. Hotspots and their determinants have a profound effect on the genomic landscape, and share certain features that extend across the tree of life. Drosophila, in contrast, are anomalous in their absence of hotspots, PRDM9, and other species-specific differences in the determination of recombination. To better understand the evolution of meiosis and general patterns of recombination across diverse taxa, we present a truly comprehensive portrait of recombination across time, combining recently published cross-based contemporary recombination estimates from each of two sister species with newly obtained linkage-disequilibrium-based historic estimates of recombination from both of these species. Using Drosophila pseudoobscura and Drosophila miranda as a model system, we compare recombination rate between species at multiple scales, and we suggest that Drosophila replicate the pattern seen in human–chimpanzee in which recombination rate is conserved at broad scales. We also find evidence of a species-wide recombination modifier(s), resulting in both a present and historic genome-wide elevation of recombination rates in D. miranda, and identify broad scale effects on recombination from the presence of an inversion. Finally, we reveal an unprecedented view of the distribution of recombination in D. pseudoobscura, illustrating patterns of linked selection and where recombination is taking place. Overall, by combining these estimation approaches, we highlight key similarities and differences in recombination between Drosophila and other organisms. PMID:26430062

Differential Rationality and Personal Development.

Science.gov (United States)

Fincher, Cameron

This publication discusses differential rationality; it asserts that the development of institutions, professions, and individuals involves the differentiation of forms and styles of thinking and knowing that are, in various ways, idiosyncratic. Based on this understanding, differential rationality can be seen as a developmental construct that…

Rational reconstructions of modern physics

CERN Document Server

Mittelstaedt, Peter

2013-01-01

Newton’s classical physics and its underlying ontology are loaded with several metaphysical hypotheses that cannot be justified by rational reasoning nor by experimental evidence. Furthermore, it is well known that some of these hypotheses are not contained in the great theories of Modern Physics, such as the theory of Special Relativity and Quantum Mechanics. This book shows that, on the basis of Newton’s classical physics and by rational reconstruction, the theory of Special Relativity as well as Quantum Mechanics can be obtained by partly eliminating or attenuating the metaphysical hypotheses. Moreover, it is shown that these reconstructions do not require additional hypotheses or new experimental results. In the second edition the rational reconstructions are completed with respect to General Relativity and Cosmology. In addition, the statistics of quantum objects is elaborated in more detail with respect to the rational reconstruction of quantum mechanics. The new material completes the approach of t...

Rational Choice and the Framing of Decisions.

Science.gov (United States)

1986-05-29

survival in a competitive environment , and a minority of rational individuals can sometimes impose rationality on the whole market. Third, the...intuitive appeal of the axioms of rational choice makes it plausible that the theory derived from these axioms should provide an acceptable account of choice...rn-use U? RATIONAL CHOICE AMD THE FINNING OF KCISIOUS(U mi/ STANFORD UNIV CR A TYERSEY ET AL. 29 NAYN4-S4-K-S61SWICLASS IF lED FO 5/10S IL EEEEEEEE

Intergroup conflict and rational decision making.

Science.gov (United States)

Martínez-Tur, Vicente; Peñarroja, Vicente; Serrano, Miguel A; Hidalgo, Vanesa; Moliner, Carolina; Salvador, Alicia; Alacreu-Crespo, Adrián; Gracia, Esther; Molina, Agustín

2014-01-01

The literature has been relatively silent about post-conflict processes. However, understanding the way humans deal with post-conflict situations is a challenge in our societies. With this in mind, we focus the present study on the rationality of cooperative decision making after an intergroup conflict, i.e., the extent to which groups take advantage of post-conflict situations to obtain benefits from collaborating with the other group involved in the conflict. Based on dual-process theories of thinking and affect heuristic, we propose that intergroup conflict hinders the rationality of cooperative decision making. We also hypothesize that this rationality improves when groups are involved in an in-group deliberative discussion. Results of a laboratory experiment support the idea that intergroup conflict -associated with indicators of the activation of negative feelings (negative affect state and heart rate)- has a negative effect on the aforementioned rationality over time and on both group and individual decision making. Although intergroup conflict leads to sub-optimal decision making, rationality improves when groups and individuals subjected to intergroup conflict make decisions after an in-group deliberative discussion. Additionally, the increased rationality of the group decision making after the deliberative discussion is transferred to subsequent individual decision making.

Intergroup Conflict and Rational Decision Making

Science.gov (United States)

Martínez-Tur, Vicente; Peñarroja, Vicente; Serrano, Miguel A.; Hidalgo, Vanesa; Moliner, Carolina; Salvador, Alicia; Alacreu-Crespo, Adrián; Gracia, Esther; Molina, Agustín

2014-01-01

The literature has been relatively silent about post-conflict processes. However, understanding the way humans deal with post-conflict situations is a challenge in our societies. With this in mind, we focus the present study on the rationality of cooperative decision making after an intergroup conflict, i.e., the extent to which groups take advantage of post-conflict situations to obtain benefits from collaborating with the other group involved in the conflict. Based on dual-process theories of thinking and affect heuristic, we propose that intergroup conflict hinders the rationality of cooperative decision making. We also hypothesize that this rationality improves when groups are involved in an in-group deliberative discussion. Results of a laboratory experiment support the idea that intergroup conflict –associated with indicators of the activation of negative feelings (negative affect state and heart rate)– has a negative effect on the aforementioned rationality over time and on both group and individual decision making. Although intergroup conflict leads to sub-optimal decision making, rationality improves when groups and individuals subjected to intergroup conflict make decisions after an in-group deliberative discussion. Additionally, the increased rationality of the group decision making after the deliberative discussion is transferred to subsequent individual decision making. PMID:25461384

Intergroup conflict and rational decision making.

Directory of Open Access Journals (Sweden)

Vicente Martínez-Tur

Full Text Available The literature has been relatively silent about post-conflict processes. However, understanding the way humans deal with post-conflict situations is a challenge in our societies. With this in mind, we focus the present study on the rationality of cooperative decision making after an intergroup conflict, i.e., the extent to which groups take advantage of post-conflict situations to obtain benefits from collaborating with the other group involved in the conflict. Based on dual-process theories of thinking and affect heuristic, we propose that intergroup conflict hinders the rationality of cooperative decision making. We also hypothesize that this rationality improves when groups are involved in an in-group deliberative discussion. Results of a laboratory experiment support the idea that intergroup conflict -associated with indicators of the activation of negative feelings (negative affect state and heart rate- has a negative effect on the aforementioned rationality over time and on both group and individual decision making. Although intergroup conflict leads to sub-optimal decision making, rationality improves when groups and individuals subjected to intergroup conflict make decisions after an in-group deliberative discussion. Additionally, the increased rationality of the group decision making after the deliberative discussion is transferred to subsequent individual decision making.

Laser-induced electron--ion recombination used to study enhanced spontaneous recombination during electron cooling

International Nuclear Information System (INIS)

Schramm, U.; Wolf, A.; Schuess ler, T.; Habs, D.; Schwalm, D.; Uwira, O.; Linkemann, J.; Mueller, A.

1997-01-01

Spontaneous recombination of highly charged ions with free electrons in merged velocity matched electron and ion beams has been observed in earlier experiments to occur at rates significantly higher than predicted by theoretical estimates. To study this enhanced spontaneous recombination, laser induced recombination spectra were measured both in velocity matched beams and in beams with well defined relative velocities, corresponding to relative electron-ion detuning energies ranging from 1 meV up to 6.5 meV where the spontaneous recombination enhancement was found to be strongly reduced. Based on a comparison with simplified calculations, the development of the recombination spectra for decreasing detuning energies indicates additional contributions at matched velocities which could be related to the energy distribution of electrons causing the spontaneous recombination rate enhancement

Rational Design of Improved Pharmabiotics

Directory of Open Access Journals (Sweden)

Roy D. Sleator

2009-01-01

Full Text Available Herein we review the most recent advances in probiotic research and applications with particular emphasis on the novel concept of patho-biotechnology: the application of pathogen-derived (ex vivo and in vivo stress survival strategies for the design of more technologically robust and effective probiotic cultures with improved biotechnological and clinical applications.

Rational design and enantioselective synthesis of (1R,4S,5R,6S)-3-azabicyclo[3.3.0]octane-4,6-dicarboxylic acid - a novel inhibitor at human glutamate transporter subtypes 1, 2, and 3

DEFF Research Database (Denmark)

Bunch, Lennart; Nielsen, Birgitte; Jensen, Anders A.

2006-01-01

The natural product kainic acid is used as template for the rational design of a novel conformationally restricted (S)-glutamic acid (Glu) analogue, (1R,4S,5R,6S)-3-azabicyclo[3.3.0]octane-4,6-dicarboxylic acid (1a). The target structure 1a was synthesized from commercially available (S)-pyroglut......The natural product kainic acid is used as template for the rational design of a novel conformationally restricted (S)-glutamic acid (Glu) analogue, (1R,4S,5R,6S)-3-azabicyclo[3.3.0]octane-4,6-dicarboxylic acid (1a). The target structure 1a was synthesized from commercially available (S...

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

Science.gov (United States)

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)

[Construction and selection of effective mouse Smad6 recombinant lenti-virus interference vectors].

Science.gov (United States)

Yu, Jing; Qi, Mengchun; Deng, Jiupeng; Liu, Gang; Chen, Huaiqing

2010-10-01

This experiment was designed to construct mouse Smad6 recombinant RNA interference vectors and determine their interference effects on bone marrow mesenchymal stem cells (BMSCs). Three recombinant Smad6 RNA interference vectors were constructed by molecular clone techniques with a lenti-virus vector expressing green fluorescent protein (GFP), and the correctness of recombinant vectors was verified by DNA sequencing. Mouse BMSCs were used for transfection experiments and BMP-2 was in use for osteogenic induction of MSCs. The transfection efficiency of recombinant vectors was examined by Laser confocal scanning microscope and the interference effect of recombinant vectors on Smad6 gene expression was determined by real-time RT-PCR and Western blot, respectively. Three Smad6 recombinant RNA interference vectors were successfully constructed and their correctness was proved by DNA sequencing. After transfection, GFPs were effectively expressed in MSCs and all of three recombinant vectors gained high transfection efficiency (> 95%). Both real-time PCR and Western blot examination indicated that among three recombinant vectors, No. 2 Svector had the best interference effect and the interference effect was nearly 91% at protein level. In conclusion, Mouse recombinant Smad6 RNA interference (RNAi) vector was successfully constructed and it provided an effective tool for further studies on BMP signal pathways.

Rational customs clearance technology choice

OpenAIRE

Shramenko, N.; Andriets, V.

2008-01-01

Issues concerning cargo delivery efficiencyincrease by choice of rational customs clearance technology have been considered. Three possible variants of customs clearance andmethods which allow to define the most rational version of cargo delivery in international road communication based on main efficiency criteria for definite distance have been presented.

Improving ethanol fermentation performance of Saccharomyces cerevisiae in very high-gravity fermentation through chemical mutagenesis and meiotic recombination

Energy Technology Data Exchange (ETDEWEB)

Liu, Jing-Jing; Ding, Wen-Tao; Zhang, Guo-Chang; Wang, Jing-Yu [Tianjin Univ. (China). Dept. of Biochemical Engineering

2011-08-15

Genome shuffling is an efficient way to improve complex phenotypes under the control of multiple genes. For the improvement of strain's performance in very high-gravity (VHG) fermentation, we developed a new method of genome shuffling. A diploid ste2/ste2 strain was subjected to EMS (ethyl methanesulfonate) mutagenesis followed by meiotic recombination-mediated genome shuffling. The resulting haploid progenies were intrapopulation sterile and therefore haploid recombinant cells with improved phenotypes were directly selected under selection condition. In VHG fermentation, strain WS1D and WS5D obtained by this approach exhibited remarkably enhanced tolerance to ethanol and osmolarity, increased metabolic rate, and 15.12% and 15.59% increased ethanol yield compared to the starting strain W303D, respectively. These results verified the feasibility of the strain improvement strategy and suggested that it is a powerful and high throughput method for development of Saccharomyces cerevisiae strains with desired phenotypes that is complex and cannot be addressed with rational approaches. (orig.)

Rationally Designed Peptides and Peptidomimetics as Inhibitors of Amyloid-β (Aβ) Aggregation: Potential Therapeutics of Alzheimer's Disease.

Science.gov (United States)

Goyal, Deepti; Shuaib, Suniba; Mann, Sukhmani; Goyal, Bhupesh

2017-02-13

Alzheimer's disease (AD) is a progressive neurodegenerative disease with no clinically accepted treatment to cure or halt its progression. The worldwide effort to develop peptide-based inhibitors of amyloid-β (Aβ) aggregation can be considered an unplanned combinatorial experiment. An understanding of what has been done and achieved may advance our understanding of AD pathology and the discovery of effective therapeutic agents. We review here the history of such peptide-based inhibitors, including those based on the Aβ sequence and those not derived from that sequence, containing both natural and unnatural amino acid building blocks. Peptide-based aggregation inhibitors hold significant promise for future AD therapy owing to their high selectivity, effectiveness, low toxicity, good tolerance, low accumulation in tissues, high chemical and biological diversity, possibility of rational design, and highly developed methods for analyzing their mode of action, proteolytic stability (modified peptides), and blood-brain barrier (BBB) permeability.

Recombining without Hotspots: A Comprehensive Evolutionary Portrait of Recombination in Two Closely Related Species of Drosophila.

Science.gov (United States)

Smukowski Heil, Caiti S; Ellison, Chris; Dubin, Matthew; Noor, Mohamed A F

2015-10-01

Meiotic recombination rate varies across the genome within and between individuals, populations, and species in virtually all taxa studied. In almost every species, this variation takes the form of discrete recombination hotspots, determined in some mammals by a protein called PRDM9. Hotspots and their determinants have a profound effect on the genomic landscape, and share certain features that extend across the tree of life. Drosophila, in contrast, are anomalous in their absence of hotspots, PRDM9, and other species-specific differences in the determination of recombination. To better understand the evolution of meiosis and general patterns of recombination across diverse taxa, we present a truly comprehensive portrait of recombination across time, combining recently published cross-based contemporary recombination estimates from each of two sister species with newly obtained linkage-disequilibrium-based historic estimates of recombination from both of these species. Using Drosophila pseudoobscura and Drosophila miranda as a model system, we compare recombination rate between species at multiple scales, and we suggest that Drosophila replicate the pattern seen in human-chimpanzee in which recombination rate is conserved at broad scales. We also find evidence of a species-wide recombination modifier(s), resulting in both a present and historic genome-wide elevation of recombination rates in D. miranda, and identify broad scale effects on recombination from the presence of an inversion. Finally, we reveal an unprecedented view of the distribution of recombination in D. pseudoobscura, illustrating patterns of linked selection and where recombination is taking place. Overall, by combining these estimation approaches, we highlight key similarities and differences in recombination between Drosophila and other organisms. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Cognitive Rationality and Its Logic-Mathematical Language

Science.gov (United States)

Masalova, Svetlana

2012-01-01

The article deals with the cognitive (flexible) rationality, combining rational and irrational moments of the scientific search of the cognizing subject. Linguo-cognitive model of the concept as the flexible regulative rationality reveals the activity of the cognitive processes and the mentality of the epistemological-ontic subject, its leading…

Therapeutic Recombinant Monoclonal Antibodies

Science.gov (United States)

Bakhtiar, Ray

2012-01-01

During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

Tunable recombinant protein expression with E. coli in a mixed-feed environment.

Science.gov (United States)

Sagmeister, Patrick; Schimek, Clemens; Meitz, Andrea; Herwig, Christoph; Spadiut, Oliver

2014-04-01

Controlling the recombinant protein production rate in Escherichia coli is of utmost importance to ensure product quality and quantity. Up to now, only the genetic construct, introduced into E. coli, and the specific growth rate of the culture were used to influence and stir the productivity. However, bioprocess technological means to control or even tune the productivity of E. coli are scarce. Here, we present a novel method for the process-technological control over the recombinant protein expression rate in E. coli. A mixed-feed fed-batch bioprocess based on the araBAD promoter expression system using both D-glucose and L-arabinose as assimilable C-sources was designed. Using the model product green fluorescent protein, we show that the specific product formation rate can be efficiently tuned even on the cellular level only via the uptake rate of L-arabinose. This novel approach introduces an additional degree of freedom for the design of recombinant bioprocesses with E. coli. We anticipate that the presented method will result in significant quality and robustness improvement as well as cost and process time reduction for recombinant bacterial bioprocesses in the future.

Purification of a Recombinant Glutathione Transferase from the Causative Agent of Hydatidosis, "Echinococcus granulosus"

Science.gov (United States)

Fleitas, Andrea L.; Randall, Lía M.; Möller, Matías N.; Denicola, Ana

2016-01-01

This practical class activity was designed to introduce students to recombinant protein expression and purification. The principal goal is to shed light on basic aspects concerning recombinant protein production, in particular protein expression, chromatography methods for protein purification, and enzyme activity as a tool to evaluate purity and…

Pressure for Pattern-Specific Intertypic Recombination between Sabin Polioviruses: Evolutionary Implications.

Science.gov (United States)

Korotkova, Ekaterina; Laassri, Majid; Zagorodnyaya, Tatiana; Petrovskaya, Svetlana; Rodionova, Elvira; Cherkasova, Elena; Gmyl, Anatoly; Ivanova, Olga E; Eremeeva, Tatyana P; Lipskaya, Galina Y; Agol, Vadim I; Chumakov, Konstantin

2017-11-22

Complete genomic sequences of a non-redundant set of 70 recombinants between three serotypes of attenuated Sabin polioviruses as well as location (based on partial sequencing) of crossover sites of 28 additional recombinants were determined and compared with the previously published data. It is demonstrated that the genomes of Sabin viruses contain distinct strain-specific segments that are eliminated by recombination. The presumed low fitness of these segments could be linked to mutations acquired upon derivation of the vaccine strains and/or may have been present in wild-type parents of Sabin viruses. These "weak" segments contribute to the propensity of these viruses to recombine with each other and with other enteroviruses as well as determine the choice of crossover sites. The knowledge of location of such segments opens additional possibilities for the design of more genetically stable and/or more attenuated variants, i.e., candidates for new oral polio vaccines. The results also suggest that the genome of wild polioviruses, and, by generalization, of other RNA viruses, may harbor hidden low-fitness segments that can be readily eliminated only by recombination.

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

Science.gov (United States)

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 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

Probabilistic approach to rationalization of plants maintenance

International Nuclear Information System (INIS)

Kasai, Masao; Notoya, Junichi; Uchimoto, Tetsuya; Miya, Kenzo

2001-01-01

Since there are a lot of equipments in large plants, their safety and reliability cannot be kept as high level as designed without maintenance activities. Then preventive maintenance is intensively executed in some large plants. However, it will be inefficient to perform the preventive maintenance blindly. To make maintenance activities effective, it is essential to identify the critical equipments influencing plant safety and/or reliability and carry out the maintenance by focusing attentions on these equipments. It needs quantitative analyses to identify the critical equipments based on the data of failure rates. However, complete data set of failure rates cannot necessarily be available for some plants such as nuclear power plants. In this study, we carry out the reliability analysis for generic LNG plant and calculate various quantitative risk importance measures for each equipment. We propose rather qualitative representations for some quantitative measures, considering the situation without complete data set and conclude that it is possible to rationalize maintenance procedure by using these rather qualitative measures, though the level of rationalization is of course limited. (author)

Medium optimization for the production of recombinant nattokinase by Bacillus subtilis using response surface methodology.

Science.gov (United States)

Chen, Po Ting; Chiang, Chung-Jen; Chao, Yun-Peng

2007-01-01

Nattokinase is a potent fibrinolytic enzyme with the potential for fighting cardiovascular diseases. Most recently, a new Bacillus subtilis/Escherichia coli (B. subtilis/E. coli) shuttle vector has been developed to achieve stable production of recombinant nattokinase in B. subtilis (Chen; et al. 2007, 23, 808-813). With this developed B. subtilis strain, the design of an optimum but cost-effective medium for high-level production of recombinant nattokinase was attempted by using response surface methodology. On the basis of the Plackett-Burman design, three critical medium components were selected. Subsequently, the optimum combination of selected factors was investigated by the Box-Behnken design. As a result, it gave the predicted maximum production of recombinant nattokinase with 71 500 CU/mL for shake-flask cultures when the concentrations of soybean hydrolysate, potassium phosphate, and calcium chloride in medium were at 6.100, 0.415, and 0.015%, respectively. This was further verified by a duplicated experiment. Moreover, the production scheme based on the optimum medium was scaled up in a fermenter. The batch fermentation of 3 L was carried out by controlling the condition at 37 degrees C and dissolved oxygen reaching 20% of air saturation level while the fermentation pH was initially set at 8.5. Without the need for controlling the broth pH, recombinant nattokinase production with a yield of 77 400 CU/mL (corresponding to 560 mg/L) could be obtained in the culture broth within 24 h. In particular, the recombinant B. subtilis strain was found fully stable at the end of fermentation when grown on the optimum medium. Overall, it indicates the success of this experimental design approach in formulating a simple and cost-effective medium, which provides the developed strain with sufficient nutrient supplements for stable and high-level production of recombinant nattokinase in a fermenter.

Book Selection, Collection Development, and Bounded Rationality.

Science.gov (United States)

Schwartz, Charles A.

1989-01-01

Reviews previously proposed schemes of classical rationality in book selection, describes new approaches to rational choice behavior, and presents a model of book selection based on bounded rationality in a garbage can decision process. The role of tacit knowledge and symbolic content in the selection process are also discussed. (102 references)…

Love and rationality: on some possible rational effects of love

Directory of Open Access Journals (Sweden)

Gustavo Ortiz-Millán

2007-01-01

Full Text Available In this paper I defend the idea that rather than disrupting rationality, as the common-sense conception has done it, love may actually help us to develop rational ways of thinking and acting. I make the case for romantic or erotic love, since this is the kind of love that is more frequently associated with irrationality in acting and thinking. I argue that this kind of love may make us develop epistemic and practical forms of rationality. Based on an analysis of its characteristic action tendencies, I argue that love may help us to develop an instrumental form of rationality in determining the best means to achieve the object of love. It may also narrow down the number of practical considerations that may help us to achieve our goals. Finally, love may generate rational ways of belief-formation by framing the parameters taken into account in perception and attention, and by bringing into light only a small portion of the epistemic information available. Love may make us perceive reality more acutely.Neste artigo defendo a idéia de que, em vez de perturbar a racionalidade, como a concepção do senso comum o faz, o amor pode, na verdade, ajudar-nos a desenvolver modos racionais de pensar e agir. Dou bons argumentos para o amor romântico ou erótico, uma vez que esse é o tipo de amor que é mais freqüentemente associado à irracionalidade no agir e no pensar. Argumento que esse tipo de amor pode fazer-nos desenvolver formas epistêmicas e práticas de racionalidade. Com base em uma análise de suas tendências características para a ação, argumento que o amor pode ajudar-nos a desenvolver uma forma instrumental de racionalidade para se determinar o melhor meio de atingir o objeto de amor. Ele também pode limitar o número de considerações práticas que podem ajudar-nos a atingir os nossos objetivos. Finalmente, o amor pode gerar modos racionais de formação de crenças ao estruturar os parâmetros considerados na percepção e na aten

A discussion of theoretical and practical rationality

Energy Technology Data Exchange (ETDEWEB)

Wahlstroem, B. [Technical Research Centre of Finland, Espoo (Finland). VTT Automation

1999-12-01

Theoretical rationality as defined in Expected Utility Theory and amended with other considerations gives a good basis for decision making. One should however always keep in mind that practical rationality often is far more complicated. People use their everyday experience when placed before new problems and this may lead to apparently irrational choices which on a closer scrutiny may be completely rational. Theories in human decision making unfortunately becomes untestable, firstly because a theory taking all considerations into account would be to complex to be practical and secondly because the data needed to test the theory cannot be collected. The benefit of EUT is that it is simple and straightforward as compared with competing theories. In the natural sciences rationality is often seen simply as a problem of optimisation. This view is practical, but it has to include also psychological and sociological considerations. The apparent controversy between natural and behavioural sciences could at least in principle be resolved by a better understanding of the complexity of human rationality. The human mind does not work in isolation, but it is adapted to a social community and a continuously changing environment. Understanding all components of human rationality is a challenge which cannot be solved on a short term basis. An important part of human rationality is connected to the intricate balance between individual and societal utility. The human mind has over thousands of years learnt to resolve that balance, but in the modern society there are decisions which may not be solvable with an intuitive approach and a strategy of trial and error. For these decisions more solid theories of rationality will be needed. EUT can in spite of its dismerits be used as the backbone for such a theory, but it has to be extended with better explanations of both individual and social rationality. If this understanding of the practical aspects of human rationality can be reached

A discussion of theoretical and practical rationality

International Nuclear Information System (INIS)

Wahlstroem, B.

1999-01-01

Theoretical rationality as defined in Expected Utility Theory and amended with other considerations gives a good basis for decision making. One should however always keep in mind that practical rationality often is far more complicated. People use their everyday experience when placed before new problems and this may lead to apparently irrational choices which on a closer scrutiny may be completely rational. Theories in human decision making unfortunately becomes untestable, firstly because a theory taking all considerations into account would be to complex to be practical and secondly because the data needed to test the theory cannot be collected. The benefit of EUT is that it is simple and straightforward as compared with competing theories. In the natural sciences rationality is often seen simply as a problem of optimisation. This view is practical, but it has to include also psychological and sociological considerations. The apparent controversy between natural and behavioural sciences could at least in principle be resolved by a better understanding of the complexity of human rationality. The human mind does not work in isolation, but it is adapted to a social community and a continuously changing environment. Understanding all components of human rationality is a challenge which cannot be solved on a short term basis. An important part of human rationality is connected to the intricate balance between individual and societal utility. The human mind has over thousands of years learnt to resolve that balance, but in the modern society there are decisions which may not be solvable with an intuitive approach and a strategy of trial and error. For these decisions more solid theories of rationality will be needed. EUT can in spite of its dismerits be used as the backbone for such a theory, but it has to be extended with better explanations of both individual and social rationality. If this understanding of the practical aspects of human rationality can be reached

Insights into the Functions of a Prophage Recombination Directionality Factor

Directory of Open Access Journals (Sweden)

Mireille Ansaldi

2012-10-01

Full Text Available Recombination directionality factors (RDFs, or excisionases, are essential players of prophage excisive recombination. Despite the essentially catalytic role of the integrase in both integrative and excisive recombination, RDFs are required to direct the reaction towards excision and to prevent re-integration of the prophage genome when entering a lytic cycle. KplE1, HK620 and numerous (prophages that integrate at the same site in enterobacteria genomes (such as the argW tRNA gene all share a highly conserved recombination module. This module comprises the attL and attR recombination sites and the RDF and integrase genes. The KplE1 RDF was named TorI after its initial identification as a negative regulator of the tor operon. However, it was characterized as an essential factor of excisive recombination. In this study, we designed an extensive random mutagenesis protocol of the torI gene and identified key residues involved in both functions of the TorI protein. We show that, in addition to TorI-TorR protein-protein interaction, TorI interacts in solution with the IntS integrase. Moreover, in vitro, TorR and IntS appear to compete for TorI binding. Finally, our mutagenesis results suggest that the C-terminal part of the TorI protein is dedicated to protein-protein interactions with both proteins TorR and IntS.

THE HICKSIAN RATIONAL CONSUMER

OpenAIRE

Manuel FERNÁNDEZ-GRELA

2005-01-01

The aim of this paper is to trace the evolution of the concept of ''rational consumer'' in Hicks's writings. After being one of the pioneers in the introduction of rationality assumptions about consumer behaviour in economic models, Hicks gradually developed a sceptical view about some of the uses to which those assumptions were put into. The focus of the paper is on continuity in Hicksian views, providing a picture of gradual changes in the long series of Hicks's works

Coping More Effectively Through Rational Self-Counseling.

Science.gov (United States)

Rogers, George W., Jr.

1981-01-01

Rational Self-Counseling, a variation of rational-emotive therapy, is a self-help therapeutic technique in which students are encouraged to be responsible for their own behavior and emotions. The primary function of self-counseling is to evaluate whether thoughts are rational. A list of questions which students might ask themselves is presented.…

Freedom and Rationality : Rousseau on Citizenship

OpenAIRE

Salvat, Christophe

2008-01-01

This paper deals with Rousseau's idea of freedom in terms of rationality and deliberation. It gives support to Berlin's interpretation of the general will as a rational and objective will but dismisses the idea that Rousseau's theory necessarily leads to authoritarianism. The general will, publicly expressed by the law, may be defined as the rational and self-regarding will agents would have if put in an independent and objective state, i.e. the state of nature. The general and the particular...

Rational design of a fibroblast growth factor 21-based clinical candidate, LY2405319.

Directory of Open Access Journals (Sweden)

Alexei Kharitonenkov

Full Text Available Fibroblast growth factor 21 is a novel hormonal regulator with the potential to treat a broad variety of metabolic abnormalities, such as type 2 diabetes, obesity, hepatic steatosis, and cardiovascular disease. Human recombinant wild type FGF21 (FGF21 has been shown to ameliorate metabolic disorders in rodents and non-human primates. However, development of FGF21 as a drug is challenging and requires re-engineering of its amino acid sequence to improve protein expression and formulation stability. Here we report the design and characterization of a novel FGF21 variant, LY2405319. To enable the development of a potential drug product with a once-daily dosing profile, in a preserved, multi-use formulation, an additional disulfide bond was introduced in FGF21 through Leu118Cys and Ala134Cys mutations. FGF21 was further optimized by deleting the four N-terminal amino acids, His-Pro-Ile-Pro (HPIP, which was subject to proteolytic cleavage. In addition, to eliminate an O-linked glycosylation site in yeast a Ser167Ala mutation was introduced, thus allowing large-scale, homogenous protein production in Pichia pastoris. Altogether re-engineering of FGF21 led to significant improvements in its biopharmaceutical properties. The impact of these changes was assessed in a panel of in vitro and in vivo assays, which confirmed that biological properties of LY2405319 were essentially identical to FGF21. Specifically, subcutaneous administration of LY2405319 in ob/ob and diet-induced obese (DIO mice over 7-14 days resulted in a 25-50% lowering of plasma glucose coupled with a 10-30% reduction in body weight. Thus, LY2405319 exhibited all the biopharmaceutical and biological properties required for initiation of a clinical program designed to test the hypothesis that administration of exogenous FGF21 would result in effects on disease-related metabolic parameters in humans.

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

Science.gov (United States)

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.

Rational choice in field archaelology

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Cătălin Pavel

2011-11-01

Full Text Available In the present article I attempt to apply advances in the study of instrumental and epistemic rationality to field archaeology in order to gain insights into the ways archaeologists reason. The cognitive processes, particularly processes of decision making, that enable archaeologists to conduct the excavation in the trench have not been adequately studied so far. I take my cues from two different bodies of theory. I first inquire into the potential that rational choice theory (RCT may have in modeling archaeological behaviour, and I define subjective expected utility, which archaeologists attempt to maximize, in terms of knowledge acquisition and social gain. Following Elster’s criticism of RCT, I conclude that RCT’s standards for rational action do not correspond with those ostensibly used in field archaeology, but that instrumental rationality has a prominent role in the “archaeological experiment”. I further explore if models proposed as reaction to RCT may account for archaeological decision making. I focus on fast and frugal heuristics, and search for archaeological illustrations for some of the cognitive biases that are better documented in psychological literature. I document confirmation and congruence biases, the endowment effect, observer-expectancy bias, illusory correlation, clustering illusion, sunk cost bias, and anchoring, among others and I propose that some of these biases are used as cognitive tools by archaeologists at work and retain epistemic value. However, I find formal logic to be secondary in the development of archaeological reasoning, with default logic and defeasible logic being used instead. I emphasize scientific knowledge as an actively negotiated social product of human inquiry, and conclude that to describe rationality in field archaeology a bounded rationality model is the most promising avenue of investigation.

The rational maps Fλ(z)

Indian Academy of Sciences (India)

It is proved that the rational maps in the family {z → zm +λ/zd : λ ∈ C\\{0}} for integers m, d ≥ 2 ... The problem of the existence of Herman rings of a rational map has been studied by. Lyubich in [9] ..... Surveys 41(4) (1986) 35–95. [10] Milnor J ...

Optimization of Soluble Expression and Purification of Recombinant Human Rhinovirus Type-14 3C Protease Using Statistically Designed Experiments: Isolation and Characterization of the Enzyme.

Science.gov (United States)

Antoniou, Georgia; Papakyriacou, Irineos; Papaneophytou, Christos

2017-10-01

Human rhinovirus (HRV) 3C protease is widely used in recombinant protein production for various applications such as biochemical characterization and structural biology projects to separate recombinant fusion proteins from their affinity tags in order to prevent interference between these tags and the target proteins. Herein, we report the optimization of expression and purification conditions of glutathione S-transferase (GST)-tagged HRV 3C protease by statistically designed experiments. Soluble expression of GST-HRV 3C protease was initially optimized by response surface methodology (RSM), and a 5.5-fold increase in enzyme yield was achieved. Subsequently, we developed a new incomplete factorial (IF) design that examines four variables (bacterial strain, expression temperature, induction time, and inducer concentration) in a single experiment. The new design called Incomplete Factorial-Strain/Temperature/Time/Inducer (IF-STTI) was validated using three GST-tagged proteins. In all cases, IF-STTI resulted in only 10% lower expression yields than those obtained by RSM. Purification of GST-HRV 3C was optimized by an IF design that examines simultaneously the effect of the amount of resin, incubation time of cell lysate with resin, and glycerol and DTT concentration in buffers, and a further 15% increase in protease recovery was achieved. Purified GST-HRV 3C protease was active at both 4 and 25 °C in a variety of buffers.

Heterogeneity and the (de)stabilizing role of rationality

International Nuclear Information System (INIS)

Cavalli, Fausto; Naimzada, Ahmad; Pireddu, Marina

2015-01-01

Highlights: • We analyze Cournot oligopolies with heterogeneous firms of generic size. • Rational and naive players are considered. • Stability with respect to oligopoly composition is studied. • In some settings, increasing the rational firms fraction introduces instability. - Abstract: In this paper we study oligopolies of generic size consisting of heterogeneous firms, which adopt best response adjustment mechanisms with either perfect foresight (rational firms) or static expectations (naive firms). Assuming an isoelastic demand function and possibly different marginal costs for the two groups of firms, we focus on the local stability of the Nash equilibrium. We show that, with respect to the oligopoly composition, described in terms of the fraction of rational firms, different scenarios are possible. We find that a high rationality degree may not always guarantee stability, in particular when rational firms have sufficiently larger marginal costs. In fact, in this situation, increasing the fraction of rational firms can even introduce instability. Besides the usual scenarios in which replacing some naive firms with rational ones leads to a stabilization of (or at least keeps unchanged) the dynamics, we provide a family of situations, characterized by costs ratio favorable to naive firms, in which equilibrium loses its stability when naive firms are replaced by rational ones. The results we present are both analytical and simulative.

Rationality and the Logic of Good Reasons.

Science.gov (United States)

Fisher, Walter R.

This paper contends that the rationality of the logic of good reasons is constituted in its use. To support this claim, the paper presents an analysis of the relationship between being reasonable and being rational. It then considers how following the logic of good reasons leads to rationality in the behavior of individuals and groups; the latter…

Recombination methods for boron neutron capture therapy dosimetry

International Nuclear Information System (INIS)

Golnik, N.; Tulik, P.; Zielczynski, M.

2003-01-01

The radiation effects of boron neutron capture therapy (BNCT) are associated with four-dose-compartment radiation field - boron dose (from 10 B(n,α) 7 Li) reaction), proton dose from 14 N(n,p) 14 C reaction, neutron dose (mainly fast and epithermal neutrons) and gamma-ray dose (external and from capture reaction 1 H(n,γ) 2 D). Because of this the relation between the absorbed dose and the biological effects is very complex and all the above mentioned absorbed dose components should be determined. From this point of view, the recombination chambers can be very useful instruments for characterization of the BNCT beams. They can be used for determination of gamma and high-LET dose components for the characterization of radiation quality of mixed radiation fields by recombination microdosimetric method (RMM). In present work, a graphite high-pressure recombination chamber filled with nitrogen, 10 BF 3 and tissue equivalent gas was used for studies on application of RMM for BNCT dosimetry. The use of these gases or their mixtures opens a possibility to design a recombination chamber for determination of the dose fractions due to gamma radiation, fast neutrons, neutron capture on nitrogen and high LET particles from (n, 10 B) reaction in simulated tissue with different content of 10 B. (author)

Recombination every day: abundant recombination in a virus during a single multi-cellular host infection.

Directory of Open Access Journals (Sweden)

Remy Froissart

2005-03-01

Full Text Available Viral recombination can dramatically impact evolution and epidemiology. In viruses, the recombination rate depends on the frequency of genetic exchange between different viral genomes within an infected host cell and on the frequency at which such co-infections occur. While the recombination rate has been recently evaluated in experimentally co-infected cell cultures for several viruses, direct quantification at the most biologically significant level, that of a host infection, is still lacking. This study fills this gap using the cauliflower mosaic virus as a model. We distributed four neutral markers along the viral genome, and co-inoculated host plants with marker-containing and wild-type viruses. The frequency of recombinant genomes was evaluated 21 d post-inoculation. On average, over 50% of viral genomes recovered after a single host infection were recombinants, clearly indicating that recombination is very frequent in this virus. Estimates of the recombination rate show that all regions of the genome are equally affected by this process. Assuming that ten viral replication cycles occurred during our experiment-based on data on the timing of coat protein detection-the per base and replication cycle recombination rate was on the order of 2 x 10(-5 to 4 x 10(-5. This first determination of a virus recombination rate during a single multi-cellular host infection indicates that recombination is very frequent in the everyday life of this virus.

Rationality, mental causation and social sciences

OpenAIRE

Mladenović Ivan

2009-01-01

The aim of this paper is to investigate the role of mental causation in the context of rational choice theory. The author defends psychological aspect of rational explanation against the challenge of contemporary reductive materialism.

Synthetic tetracycline-inducible regulatory networks: computer-aided design of dynamic phenotypes

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Kaznessis Yiannis N

2007-01-01

Full Text Available Abstract Background Tightly regulated gene networks, precisely controlling the expression of protein molecules, have received considerable interest by the biomedical community due to their promising applications. Among the most well studied inducible transcription systems are the tetracycline regulatory expression systems based on the tetracycline resistance operon of Escherichia coli, Tet-Off (tTA and Tet-On (rtTA. Despite their initial success and improved designs, limitations still persist, such as low inducer sensitivity. Instead of looking at these networks statically, and simply changing or mutating the promoter and operator regions with trial and error, a systematic investigation of the dynamic behavior of the network can result in rational design of regulatory gene expression systems. Sophisticated algorithms can accurately capture the dynamical behavior of gene networks. With computer aided design, we aim to improve the synthesis of regulatory networks and propose new designs that enable tighter control of expression. Results In this paper we engineer novel networks by recombining existing genes or part of genes. We synthesize four novel regulatory networks based on the Tet-Off and Tet-On systems. We model all the known individual biomolecular interactions involved in transcription, translation, regulation and induction. With multiple time-scale stochastic-discrete and stochastic-continuous models we accurately capture the transient and steady state dynamics of these networks. Important biomolecular interactions are identified and the strength of the interactions engineered to satisfy design criteria. A set of clear design rules is developed and appropriate mutants of regulatory proteins and operator sites are proposed. Conclusion The complexity of biomolecular interactions is accurately captured through computer simulations. Computer simulations allow us to look into the molecular level, portray the dynamic behavior of gene regulatory

Haemostatic aspects of recombinant human erythropoietin in colorectal surgery

DEFF Research Database (Denmark)

Poulsen, K A; Qvist, N; Winther, K

1998-01-01

OBJECTIVE: To find out whether recombinant human erythropoietin (r-HuEPO) given perioperatively has any effect on haemostatic activity in patients undergoing elective colorectal resection. DESIGN: A placebo-controlled double-blind study. SETTING: Odense university hospital, Denmark. SUBJECTS: 24...

Physiological responses to rational-emotive self-verbalizations.

Science.gov (United States)

Master, S; Gershman, L

1983-12-01

This study tested Albert Ellis' Rational Emotive Therapy (RET) theory which predicts that cognitive beliefs, not the stimulus situation, generate human emotions. According to RET, emotions created by rational beliefs are adaptive, while irrational beliefs result in an unadaptive anxiety level. Results demonstrated that at high levels of problem relevance there was (1) a significantly greater GSR in direct response to the stimulus situation, and also to irrational statements, than to rational and control statements, and (2) no significant difference between rational and neutral control statements. The authors argue that these results are more parsimoniously explained by conditioning theory than by RET theory.

Towards a Characterization of Rational Expectations

OpenAIRE

Itai Arieli

2008-01-01

R. J. Aumann and J. H. Drèze (2008) define a rational expectation of a player i in a game G as the expected payo of some type of i in some belief system for G in which common knowledge of rationality and common priors obtain. Our goal is to characterize the set of rational expectations in terms of the game's payoff matrix. We provide such a characterization for a specific class of strategic games, called semi-elementary, which includes Myerson's "elementary" games.

Drug Partitioning in Micellar Media and Its Implications in Rational Drug Design: Insights with Streptomycin.

Science.gov (United States)

Judy, Eva; Pagariya, Darshna; Kishore, Nand

2018-03-20

Oral bioavailability of a drug molecule requires its effective delivery to the target site. In general, majority of synthetically developed molecular entities have high hydrophobic nature as well as low bioavailability, therefore the need for suitable delivery vehicles arises. Self-assembled structures such as micelles, niosomes, and liposomes have been used as effective delivery vehicles and studied extensively. However, the information available in literature is mostly qualitative in nature. We have quantitatively investigated the partitioning of antibiotic drug streptomycin into cationic, nonionic, and a mixture of cationic and nonionic surfactant micelles and its interaction with the transport protein serum albumin upon subsequent delivery. A combination of calorimetry and spectroscopy has been used to obtain the thermodynamic signatures associated with partitioning and interaction with the protein and the resulting conformational changes in the latter. The results have been correlated with other class of drugs of different nature to understand the role of molecular features in the partitioning process. These studies are oriented toward understanding the physical chemistry of partitioning of a variety of drug molecules into suitable delivery vehicles and hence establishing structure-property-energetics relationships. Such studies provide general guidelines toward a broader goal of rational drug design.

Children's selective trust decisions: rational competence and limiting performance factors.

Science.gov (United States)

Hermes, Jonas; Behne, Tanya; Bich, Anna Elisa; Thielert, Christa; Rakoczy, Hannes

2018-03-01

Recent research has amply documented that even preschoolers learn selectively from others, preferring, for example, reliable over unreliable and competent over incompetent models. It remains unclear, however, what the cognitive foundations of such selective learning are, in particular, whether it builds on rational inferences or on less sophisticated processes. The current study, therefore, was designed to test directly the possibility that children are in principle capable of selective learning based on rational inference, yet revert to simpler strategies such as global impression formation under certain circumstances. Preschoolers (N = 75) were shown pairs of models that either differed in their degree of competence within one domain (strong vs. weak or knowledgeable vs. ignorant) or were both highly competent, but in different domains (e.g., strong vs. knowledgeable model). In the test trials, children chose between the models for strength- or knowledge-related tasks. The results suggest that, in fact, children are capable of rational inference-based selective trust: when both models were highly competent, children preferred the model with the competence most predictive and relevant for a given task. However, when choosing between two models that differed in competence on one dimension, children reverted to halo-style wide generalizations and preferred the competent models for both relevant and irrelevant tasks. These findings suggest that the rational strategies for selective learning, that children master in principle, can get masked by various performance factors. © 2017 John Wiley & Sons Ltd.

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

Science.gov (United States)

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.

Rational inattention or rational overreaction?

DEFF Research Database (Denmark)

Browning, Martin; Hansen, Lars Gårn; Smed, Sinne

We investigate differences in how consumers of fish react to health information in the mass media. We specify a dynamic empirical model that allows for heterogeneity in all basic parameters of consumer behavior as well as in how consumers react to information. We estimate the model using a unique...... houshold panel tracking consumption, prices, news stories and media habits over 24 quarters. We fi nd that the consumers most likely to be ’rationally ignorant’ of health effects react more dramatically to health news than the consumers who most likely are well informed....

A density functional theory insight towards the rational design of ionic liquids for SO2 capture.

Science.gov (United States)

García, Gregorio; Atilhan, Mert; Aparicio, Santiago

2015-05-28

A systematic density functional theory (DFT) analysis has been carried out to obtain information at the molecular level on the key parameters related to efficient SO2 capture by ionic liquids (ILs). A set of 55 ILs, for which high gas solubility is expected, has been selected. SO2 solubility of ILs was firstly predicted based on the COSMO-RS (Conductor-like Screening Model for Real Solvents) method, which provides a good prediction of gas solubility data in ILs without prior experimental knowledge of the compounds' features. Then, interactions between SO2 and ILs were deeply analyzed through DFT simulations. This work provides valuable information about required factors at the molecular level to provide high SO2 solubility in ILs, which is crucial for further implementation of these materials in the future. In our opinion, systematic research on ILs for SO2 capture increases our knowledge about those factors which could be controlled at the molecular level, providing an approach for the rational design of task-specific ILs.

A highly efficient targeted recombination system for engineering linear chromosomes of industrial bacteria Streptomyces.

Science.gov (United States)

Pan, Hung-Yin; Chen, Carton W; Huang, Chih-Hung

2018-04-17

Soil bacteria Streptomyces are the most important producers of secondary metabolites, including most known antibiotics. These bacteria and their close relatives are unique in possessing linear chromosomes, which typically harbor 20 to 30 biosynthetic gene clusters of tens to hundreds of kb in length. Many Streptomyces chromosomes are accompanied by linear plasmids with sizes ranging from several to several hundred kb. The large linear plasmids also often contain biosynthetic gene clusters. We have developed a targeted recombination procedure for arm exchanges between a linear plasmid and a linear chromosome. A chromosomal segment inserted in an artificially constructed plasmid allows homologous recombination between the two replicons at the homology. Depending on the design, the recombination may result in two recombinant replicons or a single recombinant chromosome with the loss of the recombinant plasmid that lacks a replication origin. The efficiency of such targeted recombination ranges from 9 to 83% depending on the locations of the homology (and thus the size of the chromosomal arm exchanged), essentially eliminating the necessity of selection. The targeted recombination is useful for the efficient engineering of the Streptomyces genome for large-scale deletion, addition, and shuffling.

Rationality, mental causation and social sciences

Directory of Open Access Journals (Sweden)

Mladenović Ivan

2009-01-01

Full Text Available The aim of this paper is to investigate the role of mental causation in the context of rational choice theory. The author defends psychological aspect of rational explanation against the challenge of contemporary reductive materialism.

Regulation of Meiotic Recombination

Energy Technology Data Exchange (ETDEWEB)

Gregory p. Copenhaver

2011-11-09

Meiotic recombination results in the heritable rearrangement of DNA, primarily through reciprocal exchange between homologous chromosome or gene conversion. In plants these events are critical for ensuring proper chromosome segregation, facilitating DNA repair and providing a basis for genetic diversity. Understanding this fundamental biological mechanism will directly facilitate trait mapping, conventional plant breeding, and development of genetic engineering techniques that will help support the responsible production and conversion of renewable resources for fuels, chemicals, and the conservation of energy (1-3). Substantial progress has been made in understanding the basal recombination machinery, much of which is conserved in organisms as diverse as yeast, plants and mammals (4, 5). Significantly less is known about the factors that regulate how often and where that basal machinery acts on higher eukaryotic chromosomes. One important mechanism for regulating the frequency and distribution of meiotic recombination is crossover interference - or the ability of one recombination event to influence nearby events. The MUS81 gene is thought to play an important role in regulating the influence of interference on crossing over. The immediate goals of this project are to use reverse genetics to identify mutants in two putative MUS81 homologs in the model plant Arabidopsis thaliana, characterize those mutants and initiate a novel forward genetic screen for additional regulators of meiotic recombination. The long-term goal of the project is to understand how meiotic recombination is regulated in higher eukaryotes with an emphasis on the molecular basis of crossover interference. The ability to monitor recombination in all four meiotic products (tetrad analysis) has been a powerful tool in the arsenal of yeast geneticists. Previously, the qrt mutant of Arabidopsis, which causes the four pollen products of male meiosis to remain attached, was developed as a facile system

Pandemic ventilator rationing and appeals processes.

Science.gov (United States)

Patrone, Daniel; Resnik, David

2011-06-01

In a severe influenza pandemic, hospitals will likely experience serious and widespread shortages of patient pulmonary ventilators and of staff qualified to operate them. Deciding who will receive access to mechanical ventilation will often determine who lives and who dies. This prospect raises an important question whether pandemic preparedness plans should include some process by which individuals affected by ventilator rationing would have the opportunity to appeal adverse decisions. However, the issue of appeals processes to ventilator rationing decisions has been largely neglected in state pandemic planning efforts. If we are to devise just and effective plans for coping with a severe influenza pandemic, more attention to the issue of appeals processes for pandemic ventilator rationing decisions is needed. Arguments for and against appeals processes are considered, and some suggestions are offered to help efforts at devising more rational pandemic preparedness plans.

RATIONAL APPROXIMATIONS TO GENERALIZED HYPERGEOMETRIC FUNCTIONS.

Science.gov (United States)

Under weak restrictions on the various free parameters, general theorems for rational representations of the generalized hypergeometric functions...and certain Meijer G-functions are developed. Upon specialization, these theorems yield a sequency of rational approximations which converge to the

Many faces of rationality: Implications of the great rationality debate for clinical decision-making

OpenAIRE

Djulbegovic, B.; Elqayam, Shira

2017-01-01

open access article Given that more than 30% of healthcare costs are wasted on inappropriate care, suboptimal care is increasingly connected to the quality of medical decisions. It has been argued that personal decisions are the leading cause of death, and 80% of healthcare expenditures result from physicians' decisions. Therefore, improving healthcare necessitates improving medical decisions, ie, making decisions (more) rational. Drawing on writings fromThe Great Rationality Debate from t...

Rationalizing the Promotion of Non-Rational Behaviors in Organizations.

Science.gov (United States)

Smith, Peter A. C.; Sharma, Meenakshi

2002-01-01

Organizations must balance rational/technical efficiency and emotions. Action learning has been proven to be effective for developing emotional openness in the workplace. Facilitators of action learning should draw upon the disciplines of counseling, Gestalt, psychodynamics, and Eastern philosophies. (Contains 23 references.) (SK)

Generalized NLS hierarchies from rational W algebras

International Nuclear Information System (INIS)

Toppan, F.

1993-11-01

Finite rational W algebras are very natural structures appearing in coset constructions when a Kac-Moody subalgebra is factored out. The problem of relating these algebras to integrable hierarchies of equations is studied by showing how to associate to a rational W algebra its corresponding hierarchy. Two examples are worked out, the sl(2)/U(1) coset, leading to the Non-Linear Schroedinger hierarchy, and the U(1) coset of the Polyakov-Bershadsky W algebra, leading to a 3-field representation of the KP hierarchy already encountered in the literature. In such examples a rational algebra appears as algebra of constraints when reducing a KP hierarchy to a finite field representation. This fact arises the natural question whether rational algebras are always associated to such reductions and whether a classification of rational algebras can lead to a classification of the integrable hierarchies. (author). 19 refs

Characterization of a synthetic bacterial self-destruction device for programmed cell death and for recombinant proteins release

Directory of Open Access Journals (Sweden)

Lupotto Manuel

2011-06-01

Full Text Available Abstract Background Bacterial cell lysis is a widely studied mechanism that can be achieved through the intracellular expression of phage native lytic proteins. This mechanism can be exploited for programmed cell death and for gentle cell disruption to release recombinant proteins when in vivo secretion is not feasible. Several genetic parts for cell lysis have been developed and their quantitative characterization is an essential step to enable the engineering of synthetic lytic systems with predictable behavior. Results Here, a BioBrick™ lysis device present in the Registry of Standard Biological Parts has been quantitatively characterized. Its activity has been measured in E. coli by assembling the device under the control of a well characterized N-3-oxohexanoyl-L-homoserine lactone (HSL -inducible promoter and the transfer function, lysis dynamics, protein release capability and genotypic and phenotypic stability of the device have been evaluated. Finally, its modularity was tested by assembling the device to a different inducible promoter, which can be triggered by heat induction. Conclusions The studied device is suitable for recombinant protein release as 96% of the total amount of the intracellular proteins was successfully released into the medium. Furthermore, it has been shown that the device can be assembled to different input devices to trigger cell lysis in response to a user-defined signal. For this reason, this lysis device can be a useful tool for the rational design and construction of complex synthetic biological systems composed by biological parts with known and well characterized function. Conversely, the onset of mutants makes this device unsuitable for the programmed cell death of a bacterial population.

Communicative versus strategic rationality: Habermas theory of communicative action and the social brain.

Science.gov (United States)

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.

Recombinant lactic acid bacteria as delivery vectors of heterologous antigens: the future of vaccination?

Science.gov (United States)

Trombert, A

2015-01-01

Lactic acid bacteria (LABs) are good candidates for the development of new oral vaccines and are attractive alternatives to attenuated pathogens. This review focuses on the use of wild-type and recombinant lactococci and lactobacilli with emphasis on their molecular design, immunomodulation and treatment of bacterial infections. The majority of studies related to recombinant LABs have focused on Lactococcus lactis, however, molecular tools have been successfully used for Lactobacillus spp. Recombinant lactobacilli and lactococci have several health benefits, such as immunomodulation, restoration of the microbiota, synthesis of antimicrobial substances and inhibition of virulence factors. In addition, protective immune responses that are well tolerated are induced by the expression of heterologous antigens from recombinant probiotics.

A rational evaluation of structural design loads

International Nuclear Information System (INIS)

Tasaka, S.

1993-01-01

The reliability-based seismic design of structures is a design method ensuring that the structural seismic capacity is not less than the maximum seismic load or load effect for a prescribed value of the reliability index, wherein the design reference period, n, is used to specify the n-year maximum load. In the conventional Load and Resistance Factor Design (LRFD) method the design load is commonly determined on the basis of the n-year maximum the probability distribution of which may be given in some different ways. However, in contrast with the structural capacity the n-year maximum load usually involves much larger variabilities. The effort to decrease the variability would, hence, be effective for the purpose of avoiding nuclear power plant (NPP) structures having unnecessarily large capacities. A possible way to do this is to consider the joint probability distribution of the n-year 1st and 2nd maxima of the seismic load derived from the formula of extreme order statistics. Since the reliability index is conventionally associated with the n-year 1st maximum, the conditional probability distribution rather than the joint one of the n-year 1st maximum given a value of the n-year 2nd one will be considered. Three conditional extreme value distributions, which correspond to the usual extreme value distributions of Types I, II and III, and their statistical moments up to the second order are presented. Within the framework of the first-order second moment method, the conditional statistical moments are utilized to calculate the reliability index as well as the design value of the seismic load. The seismic load considered herein is represented by the peak ground acceleration (PGA) in n years. The present scheme is applied to evaluate the design PGA's at II sites in Japan where samples of the annual 1st and 2nd PGA's have been obtained by using historical seismic data. In this application the following two points are of our interest: (a) Define the reliability

Lying for the Greater Good: Bounded Rationality in a Team

Directory of Open Access Journals (Sweden)

Oktay Sürücü

2014-10-01

Full Text Available This paper is concerned with the interaction between fully and boundedly rational agents in situations where their interests are perfectly aligned. The cognitive limitations of the boundedly rational agent do not allow him to fully understand the market conditions and lead him to take non-optimal decisions in some situations. Using categorization to model bounded rationality, we show that the fully rational agent can nudge, i.e., he can manipulate the information he sends and decrease the expected loss caused by the boundedly rational agent. Assuming different types for the boundedly rational agent, who differ only in the categories used, we show that the fully rational agent may learn the type of the boundedly rational agent along their interaction. Using this additional information, the outcome can be improved and the amount of manipulated information can be decreased. Furthermore, as the length of the interaction increases the probability that the fully rational agent learns the type of the boundedly rational agent grows

Recombination of cluster ions

Science.gov (United States)

Johnsen, Rainer

1993-01-01

Some of our recent work on molecular band emissions from recombination of molecular dimer ions (N4(+) and CO(+) CO) is discussed. Much of the experimental work was done by Y. S. Cao; the results on N4(+) recombination have been published. A brief progress report is given on our ongoing measurements of neutral products of recombination using the flowing-afterglow Langmuir-probe technique in conjunction with laser-induced fluorescence.

In vivo production of recombinant proteins using occluded recombinant AcMNPV-derived baculovirus vectors.

Science.gov (United States)

Guijarro-Pardo, Eva; Gómez-Sebastián, Silvia; Escribano, José M

2017-12-01

Trichoplusia ni insect larvae infected with vectors derived from the Autographa californica multiple nucleopolyhedrovirus (AcMNPV), are an excellent alternative to insect cells cultured in conventional bioreactors to produce recombinant proteins because productivity and cost-efficiency reasons. However, there is still a lot of work to do to reduce the manual procedures commonly required in this production platform that limit its scalability. To increase the scalability of this platform technology, a current bottleneck to be circumvented in the future is the need of injection for the inoculation of larvae with polyhedrin negative baculovirus vectors (Polh-) because of the lack of oral infectivity of these viruses, which are commonly used for production in insect cell cultures. In this work we have developed a straightforward alternative to obtain orally infective vectors derived from AcMNPV and expressing recombinant proteins that can be administered to the insect larvae (Trichoplusia ni) by feeding, formulated in the insect diet. The approach developed was based on the use of a recombinant polyhedrin protein expressed by a recombinant vector (Polh+), able to co-occlude any recombinant Polh- baculovirus vector expressing a recombinant protein. A second alternative was developed by the generation of a dual vector co-expressing the recombinant polyhedrin protein and the foreign gene of interest to obtain the occluded viruses. Additionally, by the incorporation of a reporter gene into the helper Polh+ vector, it was possible the follow-up visualization of the co-occluded viruses infection in insect larvae and will help to homogenize infection conditions. By using these methodologies, the production of recombinant proteins in per os infected larvae, without manual infection procedures, was very similar in yield to that obtained by manual injection of recombinant Polh- AcMNPV-based vectors expressing the same proteins. However, further analyses will be required for a

Pressure for Pattern-Specific Intertypic Recombination between Sabin Polioviruses: Evolutionary Implications

Directory of Open Access Journals (Sweden)

Ekaterina Korotkova

2017-11-01

Full Text Available Complete genomic sequences of a non-redundant set of 70 recombinants between three serotypes of attenuated Sabin polioviruses as well as location (based on partial sequencing of crossover sites of 28 additional recombinants were determined and compared with the previously published data. It is demonstrated that the genomes of Sabin viruses contain distinct strain-specific segments that are eliminated by recombination. The presumed low fitness of these segments could be linked to mutations acquired upon derivation of the vaccine strains and/or may have been present in wild-type parents of Sabin viruses. These “weak” segments contribute to the propensity of these viruses to recombine with each other and with other enteroviruses as well as determine the choice of crossover sites. The knowledge of location of such segments opens additional possibilities for the design of more genetically stable and/or more attenuated variants, i.e., candidates for new oral polio vaccines. The results also suggest that the genome of wild polioviruses, and, by generalization, of other RNA viruses, may harbor hidden low-fitness segments that can be readily eliminated only by recombination.

A RATIONAL APPROACH TO SEPTIC TANK DESIGN

African Journals Online (AJOL)

2012-03-01

Mar 1, 2012 ... to obtain the volume of sludge accumulated in this time interval. Using a minimum ... Design charts and a Microsoft Excel based design programme were produced to ..... Jowett, E. C. and Lay, R. Comparative per- formance of ...

Normative and descriptive rationality: from nature to artifice and back

Science.gov (United States)

Besold, T. R.; Uckelman, S. L.

2018-03-01

Rationality plays a key role in both the study of human reasoning and Artificial Intelligence (AI). Certain notions of rationality have been adopted in AI as guides for the development of intelligent machines and these notions have been given a normative function. The notions of rationality in AI are often taken to be closely related to conceptions of rationality in human contexts. In this paper, we argue that the normative role of rationality differs in the human and artificial contexts. While rationality in human-focused fields of study is normative, prescribing how humans ought to reason, the normative conception in AI is built on a notion of human rationality which is descriptive, not normative, in the human context, as AI aims at building agents which reason as humans do. In order to make this point, we review prominent notions of rationality used in psychology, cognitive science, and (the history of) philosophy, as well as in AI, and discuss some factors that contributed to rationality being assigned the differing normative statuses in the differing fields of study. We argue that while 'rationality' is a normative notion in both AI and in human reasoning, the normativity of the AI conception of 'rationality' is grounded in a descriptive account of human rationality.

Recombination pattern reanalysis of some HIV-1 circulating recombination forms suggest the necessity and difficulty of revision.

Directory of Open Access Journals (Sweden)

Lei Jia

Full Text Available Recombination is one of the major mechanisms underlying the generation of HIV-1 variability. Currently 61 circulating recombinant forms of HIV-1 have been identified. With the development of recombination detection techniques and accumulation of HIV-1 reference stains, more accurate mosaic structures of circulating recombinant forms (CRFs, like CRF04 and CRF06, have undergone repeated analysis and upgrades. Such revisions may also be necessary for other CRFs. Unlike previous studies, whose results are based primarily on a single recombination detection program, the current study was based on multiple recombination analysis, which may have produced more impartial results.Representative references of 3 categories of intersubtype recombinants were selected, including BC recombinants (CRF07 and CRF08, BG recombinants (CRF23 and CRF24, and BF recombinants (CRF38 and CRF44. They were reanalyzed in detail using both the jumping profile hidden Markov model and RDP3.The results indicate that revisions and upgrades are very necessary and the entire re-analysis suggested 2 types of revision: (i length of inserted fragments; and (ii number of inserted fragments. The reanalysis also indicated that determination of small regions of about 200 bases or fewer should be performed with more caution.Results indicated that the involvement of multiple recombination detection programs is very necessary. Additionally, results suggested two major challenges, one involving the difficulty of accurately determining the locations of breakpoints and the second involving identification of small regions of about 200 bases or fewer with greater caution. Both indicate the complexity of HIV-1 recombination. The resolution would depend critically on development of a recombination analysis algorithm, accumulation of HIV-1 stains, and a higher sequencing quality. With the changes in recombination pattern, phylogenetic relationships of some CRFs may also change. All these results may

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

Science.gov (United States)

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

2007-08-01

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

Momentum effect in stocks’ returns between the rational and the behavioural financial theories: Proposition of the progressive rationality

Directory of Open Access Journals (Sweden)

Faten Zoghlami

2013-01-01

Full Text Available     The puzzling momentum strategies’ payoffs defied the rational financial theory asserting the stocks returns’ unpredictability. Moreover, the momentum effect persist the main stocks returns’ anomaly escaping any risk-based explanation. The resilience of this phenomenon had favoured the development of behavioural financial field, which breaks with the investor’ full rationality hypothesis. This paper attempts to reconcile between the rational and behavioural financial theories, through the introduction of the progressive rationality concept. Especially, we argue that recognizing the temporary inappropriate investors’ reactions; can resolve the puzzling momentum anomaly. To fulfil our objective, we identify the appropriate autoregressive level that captures the significant autocorrelations involved by the investors’ over and under reactions. Then, we explore the profitability of the 6/6 momentum strategy implemented on the adjusted stocks’ returns. The adjusted momentum strategy is still profitable but no longer puzzling, since the related excess return is henceforth fully captured by a β and a size effect.Key words: Tunisian momentum effect, the rational finance theory, the behavioural finance theory, the three-factorial model and the autoregressive process.

Neurophysiology and Rationality in Political Thinking.

Science.gov (United States)

Peterson, Steven A.

Research both in cognitive psychology and psychobiology suggests that political behavior is often less rational than individuals believe it to be. Information processing, memory, and decision making are interlinked processes. Studies in cognitive psychology reveal that even though decision making requires rationality, individuals often adopt…

Intensive mutagenesis of the nisin hinge leads to the rational design of enhanced derivatives.

Directory of Open Access Journals (Sweden)

Brian Healy

Full Text Available Nisin A is the most extensively studied lantibiotic and has been used as a preservative by the food industry since 1953. This 34 amino acid peptide contains three dehydrated amino acids and five thioether rings. These rings, resulting from one lanthionine and four methyllanthionine bridges, confer the peptide with its unique structure. Nisin A has two mechanisms of action, with the N-terminal domain of the peptide inhibiting cell wall synthesis through lipid II binding and the C-terminal domain responsible for pore-formation. The focus of this study is the three amino acid 'hinge' region (N 20, M 21 and K 22 which separates these two domains and allows for conformational flexibility. As all lantibiotics are gene encoded, novel variants can be generated through manipulation of the corresponding gene. A number of derivatives in which the hinge region was altered have previously been shown to possess enhanced antimicrobial activity. Here we take this approach further by employing simultaneous, indiscriminate site-saturation mutagenesis of all three hinge residues to create a novel bank of nisin derivative producers. Screening of this bank revealed that producers of peptides with hinge regions consisting of AAK, NAI and SLS displayed enhanced bioactivity against a variety of targets. These and other results suggested a preference for small, chiral amino acids within the hinge region, leading to the design and creation of producers of peptides with hinges consisting of AAA and SAA. These producers, and the corresponding peptides, exhibited enhanced bioactivity against Lactococcus lactis HP, Streptococcus agalactiae ATCC 13813, Mycobacterium smegmatis MC2155 and Staphylococcus aureus RF122 and thus represent the first example of nisin derivatives that possess enhanced activity as a consequence of rational design.

Positroids Induced by Rational Dyck Paths

OpenAIRE

Gotti, Felix

2017-01-01

A rational Dyck path of type $(m,d)$ is an increasing unit-step lattice path from $(0,0)$ to $(m,d) \\in \\mathbb{Z}^2$ that never goes above the diagonal line $y = (d/m)x$. On the other hand, a positroid of rank $d$ on the ground set $[d+m]$ is a special type of matroid coming from the totally nonnegative Grassmannian. In this paper we describe how to naturally assign a rank $d$ positroid on the ground set $[d+m]$, which we name rational Dyck positroid, to each rational Dyck path of type $(m,d...

Rationalization and the Role of the School Counselor.

Science.gov (United States)

Clark, Arthur J.

1995-01-01

Examines rationalization in counselors' interactions with students, parents, and teachers--provides examples of each kind of interaction. Describes the dynamics of rationalization in the schools and outlines interventions that may be used with students, parents, and teachers. Also explores counselors' use of rationalization and gives examples of…

Electron-ion recombination in merged beams

International Nuclear Information System (INIS)

Wolf, A.; Habs, D.; Lampert, A.; Neumann, R.; Schramm, U.; Schuessler, T.; Schwalm, D.

1993-01-01

Detailed studies of recombination processes between electrons and highly charged ions have become possible by recent improvements of merged-beams experiments. We discuss in particular measurements with stored cooled ion beams at the Test Storage Ring (TSR) in Heidelberg. The cross section of dielectronic recombination was measured with high energy resolution for few-electron systems up to the nuclear charge of Cu at a relative energy up to 2.6 keV. At low energy (∼0.1 eV) total recombination rates of several ions were measured and compared with calculated radiative recombination rates. Laser-stimulated recombination of protons and of C 6+ ions was investigated as a function of the photon energy using visible radiation. Both the total recombination rates and the stimulated recombination spectra indicate that in spite of the short interaction time in merged beams, also collisional capture of electrons into weakly bound levels (related to three-body recombination) could be important

Rationality in the Cryptographic Model

DEFF Research Database (Denmark)

Hubacek, Pavel

This thesis presents results in the field of rational cryptography. In the first part we study the use of cryptographic protocols to avoid mediation and binding commitment when implementing game theoretic equilibrium concepts. First, we concentrate on the limits of cryptographic cheap talk...... to implement correlated equilibria of two-player strategic games in a sequentially rational way. We show that there exist two-player games for which no cryptographic protocol can implement the mediator in a sequentially rational way; that is, without introducing empty threats. In the context of computational...... with appealing economic applications. Our implementation puts forward a notion of cryptographically blinded games that exploits the power of encryption to selectively restrict the information available to players about sampled action profiles, such that these desirable equilibria can be stably achieved...

Novel Adjuvants and Immunomodulators for Veterinary Vaccines

DEFF Research Database (Denmark)

Heegaard, Peter M. H.; Fang, Yongxiang; Jungersen, Gregers

2016-01-01

Adjuvants are crucial for efficacy of vaccines, especially subunit and recombinant vaccines. Rational vaccine design, including knowledge-based and molecularly defined adjuvants tailored for directing and potentiating specific types of host immune responses towards the antigens included in the va...

The Rational Patient and Beyond: Implications for Treatment Adherence in People with Psychiatric Disabilities

Science.gov (United States)

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

Recent advances in rational approaches for enzyme engineering

Directory of Open Access Journals (Sweden)

Kerstin Steiner

2012-09-01

Full Text Available Enzymes are an attractive alternative in the asymmetric syntheses of chiral building blocks. To meet the requirements of industrial biotechnology and to introduce new functionalities, the enzymes need to be optimized by protein engineering. This article specifically reviews rational approaches for enzyme engineering and de novo enzyme design involving structure-based approaches developed in recent years for improvement of the enzymes’ performance, broadened substrate range, and creation of novel functionalities to obtain products with high added value for industrial applications.

Multiple barriers to recombination between divergent HIV-1 variants revealed by a dual-marker recombination assay

DEFF Research Database (Denmark)

Nikolaitchik, Olga A; Galli, Andrea; Moore, Michael D

2011-01-01

Recombination is a major force for generating human immunodeficiency virus type 1 (HIV-1) diversity and produces numerous recombinants circulating in the human population. We previously established a cell-based system using green fluorescent protein gene (gfp) as a reporter to study the mechanisms...... of HIV-1 recombination. We now report an improved system capable of detecting recombination using authentic viral sequences. Frameshift mutations were introduced into the gag gene so that parental viruses do not express full-length Gag; however, recombination can generate a progeny virus that expresses...

Proposed standby gasoline rationing plan: public comments

Energy Technology Data Exchange (ETDEWEB)

1978-12-01

Under the proposed plan, DOE would allocate ration rights (rights to purchase gasoline) to owners of registered vehicles. All vehicles in a given class would receive the same entitlement. Essential services would receive supplemental allotments of ration rights as pririty firms. Once every 3 months, ration checks would be mailed out to all vehicle registrants, allotting them a certain amount of ration rights. These checks would then be cashed at Coupon Issuance Points, where the bearer would receive ration coupons to be used at gasoline stations. Large users of gasoline could deposit their allotment checks in accounts at ration banks. Coupons or checks would be freely exchangeable in a white market. A certain percentage of the gasoline supply would be set aside in reserve for use in national emergencies. When the plan was published in the Federal Register, public comments were requested. DOE also solicited comments from private citizens, public interest groups, business and industry, state and local governments. A total of 1126 responses were reveived and these are analyzed in this paper. The second part of the report describes how the comments were classified, and gives a statistical breakdown of the major responses. The last section is a discussion and analysis of theissue raised by commenting agencies, firms, associations, and individuals. (MCW)

Detailed modelling of processes inside a catalytic recombiner for hydrogen removal

International Nuclear Information System (INIS)

Heitsch, M.

1999-01-01

Under accidental conditions, considerable amounts of hydrogen may be released into the containment. Catalytic reacting surfaces in recombiners are a reliable method to recombine this hydrogen and other burnable gases like carbon monoxide from the atmosphere in a passive way. Many experiments have been carried out to study the main phenomena occurring inside recombiners, like the efficiency of hydrogen removal, the start-up conditions, poisoning, oxygen starvation, steam and water impact, and others. In addition, the global behavior of a given recombiner device in a larger environment has been investigated in order to demonstrate the effectiveness and to facilitate the derivation of simplified models for long term, severe accident analyses. These long-term severe accident models are complemented by detailed investigations to understand the interaction of chemistry and flow inside a recombiner box. This helps to provide the dependencies of non-measurable variables (e.g. the reaction rate distribution), of local surface temperatures etc. to make long-term or system models more reliable. It also offers possibilities for increasing the chemical efficiency by optimising the geometric design properly. Computational Fluid Dynamics (CFD) codes are available for use as development tools to include the specifics of catalytic surface reactors. The present paper describes the use of the code system CFX [1] for creating a recombiner model. Some model predictions are compared to existing test data. (author)

Rational design of reconfigurable prismatic architected materials

Science.gov (United States)

Overvelde, Johannes T. B.; Weaver, James C.; Hoberman, Chuck; Bertoldi, Katia

2017-01-01

Advances in fabrication technologies are enabling the production of architected materials with unprecedented properties. Most such materials are characterized by a fixed geometry, but in the design of some materials it is possible to incorporate internal mechanisms capable of reconfiguring their spatial architecture, and in this way to enable tunable functionality. Inspired by the structural diversity and foldability of the prismatic geometries that can be constructed using the snapology origami technique, here we introduce a robust design strategy based on space-filling tessellations of polyhedra to create three-dimensional reconfigurable materials comprising a periodic assembly of rigid plates and elastic hinges. Guided by numerical analysis and physical prototypes, we systematically explore the mobility of the designed structures and identify a wide range of qualitatively different deformations and internal rearrangements. Given that the underlying principles are scale-independent, our strategy can be applied to the design of the next generation of reconfigurable structures and materials, ranging from metre-scale transformable architectures to nanometre-scale tunable photonic systems.

Privacy-Enhancing Auctions Using Rational Cryptography

DEFF Research Database (Denmark)

Miltersen, Peter Bro; Nielsen, Jesper Buus; Triandopoulos, Nikolaos

2009-01-01

show how to use rational cryptography to approximately implement any given ex interim individually strictly rational equilibrium of such an auction without a trusted mediator through a cryptographic protocol that uses only point-to-point authenticated channels between the players. By “ex interim...

Principles of Economic Rationality in Mice.

Science.gov (United States)

Rivalan, Marion; Winter, York; Nachev, Vladislav

2017-12-12

Humans and non-human animals frequently violate principles of economic rationality, such as transitivity, independence of irrelevant alternatives, and regularity. The conditions that lead to these violations are not completely understood. Here we report a study on mice tested in automated home-cage setups using rewards of drinking water. Rewards differed in one of two dimensions, volume or probability. Our results suggest that mouse choice conforms to the principles of economic rationality for options that differ along a single reward dimension. A psychometric analysis of mouse choices further revealed that mice responded more strongly to differences in probability than to differences in volume, despite equivalence in return rates. This study also demonstrates the synergistic effect between the principles of economic rationality and psychophysics in making quantitative predictions about choices of healthy laboratory mice. This opens up new possibilities for the analyses of multi-dimensional choice and the use of mice with cognitive impairments that may violate economic rationality.

Oxygen-hydrogen recombination system

International Nuclear Information System (INIS)

Sato, Shuichiro; Takejima, Masaki.

1981-01-01

Purpose: To avoid reduction in the performance of catalyst used for an oxygen-hydrogen recombiner in the off gas processing system of a nuclear reactor. Constitution: A thermometer is provided for the detection of temperature in an oxygen-hydrogen recombiner. A cooling pipe is provided in the recombiner and cooling medium is introduced externally. The cooling medium may be water or air. In accordance with the detection value from the thermometer, ON-OFF control is carried out for a valve to control the flow rate of the cooling medium thereby rendering the temperature in the recombiner to a predetermined value. This can prevent the catalyst from being exposed to high temperature and avoid the reduction in the performance of the catalyst. (Ikeda, J.)

Sordaria, a model system to uncover links between meiotic pairing and recombination.

Science.gov (United States)

Zickler, Denise; Espagne, Eric

2016-06-01

The mycelial fungus Sordaria macrospora was first used as experimental system for meiotic recombination. This review shows that it provides also a powerful cytological system for dissecting chromosome dynamics in wild-type and mutant meioses. Fundamental cytogenetic findings include: (1) the identification of presynaptic alignment as a key step in pairing of homologous chromosomes. (2) The discovery that biochemical complexes that mediate recombination at the DNA level concomitantly mediate pairing of homologs. (3) This pairing process involves not only resolution but also avoidance of chromosomal entanglements and the resolution system includes dissolution of constraining DNA recombination interactions, achieved by a unique role of Mlh1. (4) Discovery that the central components of the synaptonemal complex directly mediate the re-localization of the recombination proteins from on-axis to in-between homologue axis positions. (5) Identification of putative STUbL protein Hei10 as a structure-based signal transduction molecule that coordinates progression and differentiation of recombinational interactions at multiple stages. (6) Discovery that a single interference process mediates both nucleation of the SC and designation of crossover sites, thereby ensuring even spacing of both features. (7) Discovery of local modulation of sister-chromatid cohesion at sites of crossover recombination. Copyright © 2016 Elsevier Ltd. All rights reserved.

Decision Making: Rational, Nonrational, and Irrational.

Science.gov (United States)

Simon, Herbert A.

1993-01-01

Describes the current state of knowledge about human decision-making and problem-solving processes, explaining recent developments and their implications for management and management training. Rational goal-setting is the key to effective decision making and accomplishment. Bounded rationality is a realistic orientation, because the world is too…

Rational Development of Addiction Pharmacotherapies: Successes, Failures, and Prospects

OpenAIRE

Christopher Pierce, R.; O’Brien, Charles P.; Kenny, Paul J.; Vanderschuren, Louk J. M. J.

2012-01-01

There are currently effective, U.S. Food and Drug Administration (FDA)-approved therapies for alcohol, nicotine, and opioid addiction. In some cases these therapeutics were rationally designed and tested using a combination of various animal models of addiction. In many cases, however, effective drug therapies for addiction were derived from the testing of compounds developed for other CNS disorders (e.g., analgesics and antidepressants), which were tested clinically in the absence of prior a...

Osteoinductive recombinant silk fusion proteins for bone regeneration.

Science.gov (United States)

Dinjaski, Nina; Plowright, Robyn; Zhou, Shun; Belton, David J; Perry, Carole C; Kaplan, David L

2017-02-01

Protein polymers provide a unique opportunity for tunable designs of material systems due to the genetic basis of sequence control. To address the challenge of biomineralization interfaces with protein based materials, we genetically engineered spider silks to design organic-inorganic hybrid systems. The spider silk inspired domain (SGRGGLGGQG AGAAAAAGGA GQGGYGGLGSQGT) 15 served as an organic scaffold to control material stability and to allow multiple modes of processing, whereas the hydroxyapatite binding domain VTKHLNQISQSY (VTK), provided control over osteogenesis. The VTK domain was fused either to the N-, C- or both terminals of the spider silk domain to understand the effect of position on material properties and mineralization. The addition of the VTK domain to silk did not affect the physical properties of the silk recombinant constructs, but it had a critical role in the induction of biomineralization. When the VTK domain was placed on both the C- and N-termini the formation of crystalline hydroxyapatite was significantly increased. In addition, all of the recombinant proteins in film format supported the growth and proliferation of human mesenchymal stem cells (hMSCs). Importantly, the presence of the VTK domain enhanced osteoinductive properties up to 3-fold compared to the control (silk alone without VTK). Therefore, silk-VTK fusion proteins have been shown suitable for mineralization and functionalization for specific biomedical applications. Organic-inorganic interfaces are integral to biomaterial functions in many areas of repair and regeneration. Several protein polymers have been investigated for this purpose. Despite their success the limited options to fine-tune their material properties, degradation patterns and functionalize them for each specific biomedical application limits their application. Various studies have shown that the biological performance of such proteins can be improved by genetic engineering. The present study provides data

Simplifications of rational matrices by using UML

OpenAIRE

Tasić, Milan B.; Stanimirović, Ivan P.

2013-01-01

The simplification process on rational matrices consists of simplifying each entry represented by a rational function. We follow the classic approach of dividing the numerator and denominator polynomials by their common GCD polynomial, and provide the activity diagram in UML for this process. A rational matrix representation as the quotient of a polynomial matrix and a polynomial is also discussed here and illustrated via activity diagrams. Also, a class diagram giving the links between the c...

Local Choices: Rationality and the Contextuality of Decision-Making

Science.gov (United States)

Vlaev, Ivo

2018-01-01

Rational explanation is ubiquitous in psychology and social sciences, ranging from rational analysis, expectancy-value theories, ideal observer models, mental logic to probabilistic frameworks, rational choice theory, and informal “folk psychological” explanation. However, rational explanation appears to be challenged by apparently systematic irrationality observed in psychological experiments, especially in the field of judgement and decision-making (JDM). Here, it is proposed that the experimental results require not that rational explanation should be rejected, but that rational explanation is local, i.e., within a context. Thus, rational models need to be supplemented with a theory of contextual shifts. We review evidence in JDM that patterns of choices are often consistent within contexts, but unstable between contexts. We also demonstrate that for a limited, though reasonably broad, class of decision-making domains, recent theoretical models can be viewed as providing theories of contextual shifts. It is argued that one particular significant source of global inconsistency arises from a cognitive inability to represent absolute magnitudes, whether for perceptual variables, utilities, payoffs, or probabilities. This overall argument provides a fresh perspective on the scope and limits of human rationality. PMID:29301289

Local Choices: Rationality and the Contextuality of Decision-Making.

Science.gov (United States)

Vlaev, Ivo

2018-01-02

Rational explanation is ubiquitous in psychology and social sciences, ranging from rational analysis, expectancy-value theories, ideal observer models, mental logic to probabilistic frameworks, rational choice theory, and informal "folk psychological" explanation. However, rational explanation appears to be challenged by apparently systematic irrationality observed in psychological experiments, especially in the field of judgement and decision-making (JDM). Here, it is proposed that the experimental results require not that rational explanation should be rejected, but that rational explanation is local , i.e., within a context. Thus, rational models need to be supplemented with a theory of contextual shifts. We review evidence in JDM that patterns of choices are often consistent within contexts, but unstable between contexts. We also demonstrate that for a limited, though reasonably broad, class of decision-making domains, recent theoretical models can be viewed as providing theories of contextual shifts. It is argued that one particular significant source of global inconsistency arises from a cognitive inability to represent absolute magnitudes, whether for perceptual variables, utilities, payoffs, or probabilities. This overall argument provides a fresh perspective on the scope and limits of human rationality.

Techno-Optimism and Rational Superstition

DEFF Research Database (Denmark)

Wilson, Alexander

2017-01-01

our common understanding of reason and rationality? To adopt rational expectations about the world, after all, should we not attempt to avoid the emotional over-determination of our assessments? I show that applied reason is conceptually entangled with this superstitious optimism in the continued...... of retro-causation, where the future is held to somehow have a retroactive effect on the past. This suggests, I argue, that the underlying mechanism by which techno-optimism is supposed to be instrumental in bringing about the future is fundamentally superstitious. But does this superstition not go against...... successes of technology. The article thus reveals a curious sense in which reason is intrinsically superstitious. I offer an evolutionary explanation for this, showing that the biological origins of reason will by nature tend to produce rational agents which are superstitiously bound to realism...

On the relict recombination lines

International Nuclear Information System (INIS)

Bershtejn, I.N.; Bernshtejn, D.N.; Dubrovich, V.K.

1977-01-01

Accurate numerical calculation of intensities and profiles of hydrogen recombination lines of cosmological origin is made. Relie radiation distortions stipulated by recombination quantum release at the irrevocable recombination are investigated. Mean number calculation is given for guantums educing for one irrevocably-lost electron. The account is taken of the educed quantums interraction with matter. The main quantum-matter interrraction mechanisms are considered: electronic blow broadening; free-free, free-bound, bound-bound absorptions Recombination dynamics is investigated depending on hydrogen density and total density of all the matter kinds in the Universe

Hydrogen initiative: An integrated approach toward rational nanocatalyst design for hydrogen production. Technical Report-Year 1

Energy Technology Data Exchange (ETDEWEB)

Vlachos, Dionisios G. [Univ. of Delaware, Newark, DE (United States); Buttrey, Douglas J. [Univ. of Delaware, Newark, DE (United States); Lauterbach, Jochen A. [Univ. of Delaware, Newark, DE (United States)

2007-03-29

The overall objective of this grant is to develop a rational framework for the discovery of low cost, robust, and active nano-catalysts that will enable efficient hydrogen production. Our approach will be the first demonstration of integrated multiscale model, nano-catalyst synthesis, and nanoscale characterization assisted high throughput experimentation (HTE). We will initially demonstrate our approach with ammonia decomposition on noble metal catalysts. Our research focuses on many elements of the Hydrogen Initiative in the Focus Area of “Design of Catalysts at the Nanoscale’. It combines high-throughput screening methods with various nanostructure synthesis protocols, advanced measurements, novel in situ and ex situ characterization techniques, and multiscale theory, modeling and simulation. This project directly addresses several of the long-term goals of the DOE/BES program. In particular, new nanoscale catalytic materials will be synthesized, characterized and modeled for the production of hydrogen from ammonia and a computational framework will be developed for efficient extraction of information from experimental data and for rational design of catalysts whose impact goes well beyond the proposed hydrogen production project. In the first year of the grant, we have carried out HTE screening using a 16 parallel microreactor coupled with an FTIR analysis system. We screened nearly twenty single metals and several bimetallic catalysts as a function of temperature, catalyst loading, inlet composition, and temperature (order of 400 experiments). We have found that Ru is the best single metal catalyst and no better catalysts were found among the library of bimetallics we have created so far. Furthermore, we have investigated promoting effects (i.e., K, Cs, and Ba) of the Ru catalyst. We have found that K is the dominant promoter of increased Ru activity. Response surface experimental design has led to substantial improvements of the Ru catalyst with promotion

Information-Theoretic Bounded Rationality and ε-Optimality

Directory of Open Access Journals (Sweden)

Daniel A. Braun

2014-08-01

Full Text Available Bounded rationality concerns the study of decision makers with limited information processing resources. Previously, the free energy difference functional has been suggested to model bounded rational decision making, as it provides a natural trade-off between an energy or utility function that is to be optimized and information processing costs that are measured by entropic search costs. The main question of this article is how the information-theoretic free energy model relates to simple ε-optimality models of bounded rational decision making, where the decision maker is satisfied with any action in an ε-neighborhood of the optimal utility. We find that the stochastic policies that optimize the free energy trade-off comply with the notion of ε-optimality. Moreover, this optimality criterion even holds when the environment is adversarial. We conclude that the study of bounded rationality based on ε-optimality criteria that abstract away from the particulars of the information processing constraints is compatible with the information-theoretic free energy model of bounded rationality.

Rationing critical care medicine: recent studies and current trends.

Science.gov (United States)

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.

Late replicating domains are highly recombining in females but have low male recombination rates: implications for isochore evolution.

Directory of Open Access Journals (Sweden)

Catherine J Pink

Full Text Available In mammals sequences that are either late replicating or highly recombining have high rates of evolution at putatively neutral sites. As early replicating domains and highly recombining domains both tend to be GC rich we a priori expect these two variables to covary. If so, the relative contribution of either of these variables to the local neutral substitution rate might have been wrongly estimated owing to covariance with the other. Against our expectations, we find that sex-averaged recombination rates show little or no correlation with replication timing, suggesting that they are independent determinants of substitution rates. However, this result masks significant sex-specific complexity: late replicating domains tend to have high recombination rates in females but low recombination rates in males. That these trends are antagonistic explains why sex-averaged recombination is not correlated with replication timing. This unexpected result has several important implications. First, although both male and female recombination rates covary significantly with intronic substitution rates, the magnitude of this correlation is moderately underestimated for male recombination and slightly overestimated for female recombination, owing to covariance with replicating timing. Second, the result could explain why male recombination is strongly correlated with GC content but female recombination is not. If to explain the correlation between GC content and replication timing we suppose that late replication forces reduced GC content, then GC promotion by biased gene conversion during female recombination is partly countered by the antagonistic effect of later replicating sequence tending increase AT content. Indeed, the strength of the correlation between female recombination rate and local GC content is more than doubled by control for replication timing. Our results underpin the need to consider sex-specific recombination rates and potential covariates in

Decision rules and group rationality: cognitive gain or standstill?

Directory of Open Access Journals (Sweden)

Petru Lucian Curşeu

Full Text Available Recent research in group cognition points towards the existence of collective cognitive competencies that transcend individual group members' cognitive competencies. Since rationality is a key cognitive competence for group decision making, and group cognition emerges from the coordination of individual cognition during social interactions, this study tests the extent to which collaborative and consultative decision rules impact the emergence of group rationality. Using a set of decision tasks adapted from the heuristics and biases literature, we evaluate rationality as the extent to which individual choices are aligned with a normative ideal. We further operationalize group rationality as cognitive synergy (the extent to which collective rationality exceeds average or best individual rationality in the group, and we test the effect of collaborative and consultative decision rules in a sample of 176 groups. Our results show that the collaborative decision rule has superior synergic effects as compared to the consultative decision rule. The ninety one groups working in a collaborative fashion made more rational choices (above and beyond the average rationality of their members than the eighty five groups working in a consultative fashion. Moreover, the groups using a collaborative decision rule were closer to the rationality of their best member than groups using consultative decision rules. Nevertheless, on average groups did not outperformed their best member. Therefore, our results reveal how decision rules prescribing interpersonal interactions impact on the emergence of collective cognitive competencies. They also open potential venues for further research on the emergence of collective rationality in human decision-making groups.

Decision rules and group rationality: cognitive gain or standstill?

Science.gov (United States)

Curşeu, Petru Lucian; Jansen, Rob J G; Chappin, Maryse M H

2013-01-01

Recent research in group cognition points towards the existence of collective cognitive competencies that transcend individual group members' cognitive competencies. Since rationality is a key cognitive competence for group decision making, and group cognition emerges from the coordination of individual cognition during social interactions, this study tests the extent to which collaborative and consultative decision rules impact the emergence of group rationality. Using a set of decision tasks adapted from the heuristics and biases literature, we evaluate rationality as the extent to which individual choices are aligned with a normative ideal. We further operationalize group rationality as cognitive synergy (the extent to which collective rationality exceeds average or best individual rationality in the group), and we test the effect of collaborative and consultative decision rules in a sample of 176 groups. Our results show that the collaborative decision rule has superior synergic effects as compared to the consultative decision rule. The ninety one groups working in a collaborative fashion made more rational choices (above and beyond the average rationality of their members) than the eighty five groups working in a consultative fashion. Moreover, the groups using a collaborative decision rule were closer to the rationality of their best member than groups using consultative decision rules. Nevertheless, on average groups did not outperformed their best member. Therefore, our results reveal how decision rules prescribing interpersonal interactions impact on the emergence of collective cognitive competencies. They also open potential venues for further research on the emergence of collective rationality in human decision-making groups.

Novel chemometric strategy based on the application of artificial neural networks to crossed mixture design for the improvement of recombinant protein production in continuous culture.

Science.gov (United States)

Didier, Caroline; Forno, Guillermina; Etcheverrigaray, Marina; Kratje, Ricardo; Goicoechea, Héctor

2009-09-21

The optimal blends of six compounds that should be present in culture media used in recombinant protein production were determined by means of artificial neural networks (ANN) coupled with crossed mixture experimental design. This combination constitutes a novel approach to develop a medium for cultivating genetically engineered mammalian cells. The compounds were collected in two mixtures of three elements each, and the experimental space was determined by a crossed mixture design. Empirical data from 51 experimental units were used in a multiresponse analysis to train artificial neural networks which satisfy different requirements, in order to define two new culture media (Medium 1 and Medium 2) to be used in a continuous biopharmaceutical production process. These media were tested in a bioreactor to produce a recombinant protein in CHO cells. Remarkably, for both predicted media all responses satisfied the predefined goals pursued during the analysis, except in the case of the specific growth rate (mu) observed for Medium 1. ANN analysis proved to be a suitable methodology to be used when dealing with complex experimental designs, as frequently occurs in the optimization of production processes in the biotechnology area. The present work is a new example of the use of ANN for the resolution of a complex, real life system, successfully employed in the context of a biopharmaceutical production process.

Development of probabilistic fast reactor fuel design method

International Nuclear Information System (INIS)

Ozawa, Takayuki

1997-01-01

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

Anxiety reduction through group instruction in rational therapy.

Science.gov (United States)

Maxwell, J W; Wilkerson, J

1982-09-01

This study investigated the effects of group Rational Therapy in promoting rational thinking and self-enhancing emotions among 24 college students. Each subject was administered the Sixteen Personality Factor Questionnaire as a pre- and post-test measurement. Results reveal that some aspects of personality are affected by Rational Therapy group programs while others are not.

Thinking about acting logical foundations for rational decision making

CERN Document Server

Pollock, John L

2006-01-01

John Pollock aims to construct a theory of rational decision making for real agents--not ideal agents. Real agents have limited cognitive powers, but traditional theories of rationality have applied only to idealized agents that lack such constraints. Pollock argues that theories of ideal rationality are largely irrelevant to the decision making of real agents. Thinking about Acting aims to provide a theory of ""real rationality.""

Choice, internal consistency, and rationality

OpenAIRE

Aditi Bhattacharyya; Prasanta K. Pattanaik; Yongsheng Xu

2010-01-01

The classical theory of rational choice is built on several important internal consistency conditions. In recent years, the reasonableness of those internal consistency conditions has been questioned and criticized, and several responses to accommodate such criticisms have been proposed in the literature. This paper develops a general framework to accommodate the issues raised by the criticisms of classical rational choice theory, and examines the broad impact of these criticisms from both no...

Management between Rationality and Irrationality

OpenAIRE

Cene Bavec

2012-01-01

In the paper, we discuss theoretical and practical aspects of management and its rational and irrational behavior in the light of traditional management theories and contemporary social theories and theories of complexity. We exposed differences between middle and top management, where rationality is ascribed mainly to middle management, while top management often acts on seemingly irrational way. For the part of this irrationality, we cannot blame management because it originates from the na...

Self-Reported Rationing Behavior Among US Physicians: A National Survey.

Science.gov (United States)

Sheeler, Robert D; Mundell, Tim; Hurst, Samia A; Goold, Susan Dorr; Thorsteinsdottir, Bjorg; Tilburt, Jon C; Danis, Marion

2016-12-01

Rationing is a controversial topic among US physicians. Understanding their attitudes and behaviors around rationing may be essential to a more open and sensible professional discourse on this important but controversial topic. To describe rationing behavior and associated factors among US physicians. Survey mailed to US physicians in 2012 to evaluate self-reported rationing behavior and variables related to this behavior. US physicians across a full spectrum of practice settings. A total of 2541 respondents, representing 65.6 % of the original mailing list of 3872 US addresses. The study was a cross-sectional analysis of physician attitudes and self-reported behaviors, with neutral language representations of the behaviors as well as an embedded experiment to test the influence of the word "ration" on perceived responsibility. Overall percentage of respondents reporting rationing behavior in various contexts and assessment of attitudes toward rationing. In total, 1348 respondents (53.1 %) reported having personally refrained within the past 6 months from using specific clinical services that would have provided the best patient care, because of health system cost. Prescription drugs (n = 1073 [48.3 %]) and magnetic resonance imaging (n = 922 [44.5 %]) were most frequently rationed. Surgical and procedural specialists were less likely to report rationing behavior (adjusted odds ratio [OR] [95 % CI], 0.8 [0.9-0.9] and 0.5 [0.4-0.6], respectively) compared to primary care. Compared with small or solo practices, those in medical school settings reported less rationing (adjusted OR [95 % CI], 0.4 [0.2-0.7]). Physicians who self-identified as very or somewhat liberal were significantly less likely to report rationing (adjusted OR [95 % CI], 0.7 [0.6-0.9]) than those self-reporting being very or somewhat conservative. A more positive opinion about rationing tended to align with greater odds of rationing. More than one-half of respondents engaged in

Rational-driver approximation in car-following theory

Science.gov (United States)

Lubashevsky, Ihor; Wagner, Peter; Mahnke, Reinhard

2003-11-01

The problem of a car following a lead car driven with constant velocity is considered. To derive the governing equations for the following car dynamics a cost functional is constructed. This functional ranks the outcomes of different driving strategies, which applies to fairly general properties of the driver behavior. Assuming rational-driver behavior, the existence of the Nash equilibrium is proved. Rational driving is defined by supposing that a driver corrects continuously the car motion to follow the optimal path minimizing the cost functional. The corresponding car-following dynamics is described quite generally by a boundary value problem based on the obtained extremal equations. Linearization of these equations around the stationary state results in a generalization of the widely used optimal velocity model. Under certain conditions (the “dense traffic” limit) the rational car dynamics comprises two stages, fast and slow. During the fast stage a driver eliminates the velocity difference between the cars, the subsequent slow stage optimizes the headway. In the dense traffic limit an effective Hamiltonian description is constructed. This allows a more detailed nonlinear analysis. Finally, the differences between rational and bounded rational driver behavior are discussed. The latter, in particular, justifies some basic assumptions used recently by the authors to construct a car-following model lying beyond the frameworks of rationality.

Rationality and ritual

International Nuclear Information System (INIS)

Wynne, B.

1982-01-01

The book concerns the Windscale Public Inquiry, held to investigate the application by British Nuclear Fuels to build a 1200 tonne per year thermal oxide reprocessing plant (THORP) for spent nuclear fuels from Britain and overseas. The subject is discussed under the headings: introduction (international dimensions; the Windscale Inquiry; conflict resolution and social drama; public debate and the sociology of knowledge); the decision-making legacy; oxide reprocessing - the background; the public inquiry tradition - a comparative perspective; the emergence of THORP from a private to a public issue (local and national planning politics); the process and impact of the Inquiry (opposition groups); judicial rationality, expert conflict, and political authority); the rationality and politics of analysis (proliferation; radiation risks; relative risks; the Ravenglass issue; discharge targets; general radiation protection arrangements); conclusion. (U.K.)

Rational accountability and rational autonomy in academic practice: An extended case study of the communicative ethic of interdisciplinary science

Science.gov (United States)

Robertson, Susan Margaret

The dissertation investigates the interaction of rational accountability and rational autonomy in interdisciplinary science within the lifeworld of the university. It focuses on the cultural, social and motivational forces that university researchers draw on, and develop, to constitute and regulate interdisciplinary science. Findings are analyzed within an applied critical social theory framework that attends to the interaction of instrumental and communicative rational action within the public spaces that constitute the lifeworld of the university as a public sphere in society. The research raises questions of how academics practice interdisciplinary science and how these practices relate to the reproduction of the regulative ideal of the university as a community that practices public reason. The conceptual framework informing the research is Habermas' (1984) theory of communicative action. Using Burawoy's (1991) extended case study method as an operational strategy, two modes of constituting and regulating interdisciplinary science were found. Instrumental rational modes dominated in social contexts of interdisciplinary science where consensus on the normative goals and purposes of rational academic action were pre-existing and pre-supposed by participants. Communicative rational modes dominated in social contexts of interdisciplinary science where the normative goals and purposes of rational academic action entered a contested domain. Endorsements for interdisciplinary science policies are coinciding with demands for increased accountability and relevance of Canada's university system. At the same time that the university system must respond to external demands, it must reproduce itself as a public institution open to the discursive redemption of factual and normative validity claims. The study found that academics participate in, but also contest the instrumental regulation of academic inquiry and conduct by using their constitutional autonomy and freedom to

Heparin-binding peptide as a novel affinity tag for purification of recombinant proteins.

Science.gov (United States)

Morris, Jacqueline; Jayanthi, Srinivas; Langston, Rebekah; Daily, Anna; Kight, Alicia; McNabb, David S; Henry, Ralph; Kumar, Thallapuranam Krishnaswamy Suresh

2016-10-01

Purification of recombinant proteins constitutes a significant part of the downstream processing in biopharmaceutical industries. Major costs involved in the production of bio-therapeutics mainly depend on the number of purification steps used during the downstream process. Affinity chromatography is a widely used method for the purification of recombinant proteins expressed in different expression host platforms. Recombinant protein purification is achieved by fusing appropriate affinity tags to either N- or C- terminus of the target recombinant proteins. Currently available protein/peptide affinity tags have proved quite useful in the purification of recombinant proteins. However, these affinity tags suffer from specific limitations in their use under different conditions of purification. In this study, we have designed a novel 34-amino acid heparin-binding affinity tag (HB-tag) for the purification of recombinant proteins expressed in Escherichia coli (E. coli) cells. HB-tag fused recombinant proteins were overexpressed in E. coli in high yields. A one-step heparin-Sepharose-based affinity chromatography protocol was developed to purify HB-fused recombinant proteins to homogeneity using a simple sodium chloride step gradient elution. The HB-tag has also been shown to facilitate the purification of target recombinant proteins from their 8 M urea denatured state(s). The HB-tag has been demonstrated to be successfully released from the fusion protein by an appropriate protease treatment to obtain the recombinant target protein(s) in high yields. Results of the two-dimensional NMR spectroscopy experiments indicate that the purified recombinant target protein(s) exist in the native conformation. Polyclonal antibodies raised against the HB-peptide sequence, exhibited high binding specificity and sensitivity to the HB-fused recombinant proteins (∼10 ng) in different crude cell extracts obtained from diverse expression hosts. In our opinion, the HB-tag provides a

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

Science.gov (United States)

Carter, Daniel C. (Inventor)

1996-01-01

Serum albumin crystal forms have been produced which exhibit superior x-ray diffraction quality. The crystals are produced from both recombinant and wild-type human serum albumin, canine, and baboon serum albumin and allow the performance of drug-binding studies as well as genetic engineering studies. The crystals are grown from solutions of polyethylene glycol or ammonium sulphate within prescribed limits during growth times from one to several weeks and include the following space groups: P2(sub 1), C2, P1.

Effects of predation stress and food ration on perch gut microbiota.

Science.gov (United States)

Zha, Yinghua; Eiler, Alexander; Johansson, Frank; Svanbäck, Richard

2018-02-06

Gut microbiota provide functions of importance to influence hosts' food digestion, metabolism, and protection against pathogens. Factors that affect the composition and functions of gut microbial communities are well studied in humans and other animals; however, we have limited knowledge of how natural food web factors such as stress from predators and food resource rations could affect hosts' gut microbiota and how it interacts with host sex. In this study, we designed a two-factorial experiment exposing perch (Perca fluviatilis) to a predator (pike, Esox lucius), and different food ratios, to examine the compositional and functional changes of perch gut microbiota based on 16S rRNA amplicon sequencing. We also investigated if those changes are host sex dependent. We showed that overall gut microbiota composition among individual perch significantly responded to food ration and predator presence. We found that species richness decreased with predator presence, and we identified 23 taxa from a diverse set of phyla that were over-represented when a predator was present. For example, Fusobacteria increased both at the lowest food ration and at predation stress conditions, suggesting that Fusobacteria are favored by stressful situations for the host. In concordance, both food ration and predation stress seemed to influence the metabolic repertoire of the gut microbiota, such as biosynthesis of other secondary metabolites, metabolism of cofactors, and vitamins. In addition, the identified interaction between food ration and sex emphasizes sex-specific responses to diet quantity in gut microbiota. Collectively, our findings emphasize an alternative state in gut microbiota with responses to changes in natural food webs depending on host sex. The obtained knowledge from this study provided us with an important perspective on gut microbiota in a food web context.

CRMAGE: CRISPR Optimized MAGE Recombineering

DEFF Research Database (Denmark)

Ronda, Carlotta; Pedersen, Lasse Ebdrup; Sommer, Morten Otto Alexander

2016-01-01

A bottleneck in metabolic engineering and systems biology approaches is the lack of efficient genome engineering technologies. Here, we combine CRISPR/Cas9 and λ Red recombineering based MAGE technology (CRMAGE) to create a highly efficient and fast method for genome engineering of Escherichia coli...... that are assembled by a USER-cloning approach enabling quick and cost efficient gRNA replacement. CRMAGE furthermore utilizes CRISPR/Cas9 for efficient plasmid curing, thereby enabling multiple engineering rounds per day. To facilitate the design process, a web-based tool was developed to predict both the λ Red...

Targeted in vivo inhibition of specific protein-protein interactions using recombinant antibodies.

Directory of Open Access Journals (Sweden)

Matej Zábrady

Full Text Available With the growing availability of genomic sequence information, there is an increasing need for gene function analysis. Antibody-mediated "silencing" represents an intriguing alternative for the precise inhibition of a particular function of biomolecules. Here, we describe a method for selecting recombinant antibodies with a specific purpose in mind, which is to inhibit intrinsic protein-protein interactions in the cytosol of plant cells. Experimental procedures were designed for conveniently evaluating desired properties of recombinant antibodies in consecutive steps. Our selection method was successfully used to develop a recombinant antibody inhibiting the interaction of ARABIDOPSIS HISTIDINE PHOSPHOTRANSFER PROTEIN 3 with such of its upstream interaction partners as the receiver domain of CYTOKININ INDEPENDENT HISTIDINE KINASE 1. The specific down-regulation of the cytokinin signaling pathway in vivo demonstrates the validity of our approach. This selection method can serve as a prototype for developing unique recombinant antibodies able to interfere with virtually any biomolecule in the living cell.

Differential effects of gamification, nudging and rational information on travel behavior

DEFF Research Database (Denmark)

Lieberoth, Andreas; Jensen, Niels Holm; Skovgaard, Thomas

visible when “players” started displaying them on their profiles. Just-in–time feedback was sent on text and email, and information on e.g. badges accumulated on the website. A prize of further free travel was offered. The rational health information approach framed the benefits of commuting in terms...... local commuters were recruited into the experiment using a traditional campaign of media appearances and outdoor advertising. Participants were divided into groups based on their place of residence. A fourth smaller control condition was also formed. Each participant received a letter of information...... particular to the influence condition, and a free travel card good for the month. Researchers from two major universities each designed an influence strategy in accordance with literature and practices in their fields, separable into gamification, nudging and rational health information. Swipes...

RATIONAL-IRRATIONAL ELECTORAL PREFERENCES, ALTRUISM AND EXPRESSIVE BEHAVIOR

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Mihai Ungureanu

2015-01-01

Full Text Available Caplan (2000, 2001, 2006 proposed the rational-irrationality model arguing that irrationality is a good as any other, whose consumption is maximized in relation to its costs and benefits. Applying this model to the problem of electoral behavior Caplan implies that voters ‘afford’ many irrational beliefs, because the lack of individual decisiveness renders vote as a consequenceless act. This paper contributes to the development of knowledge by analyzing the compatibility of rational irrationality with active electoral behavior. Two important arguments are being proposed: First, Wittman’s (2008 intuition that rational irrationality is incompatible with voting could be supported only about a particular type of altruism, which Caplan actually seems to reject. Second, rational irrationality seems to be compatible with expressive motivations, reinforcing the conclusion that rational-irrational individuals are active voters in mass elections.

The Problem of Rational Moral Enlistment

Science.gov (United States)

Tillson, John

2017-01-01

How can one bring children to recognize the requirements of morality without resorting only to non-rational means of persuasion (i.e. what rational ground can be offered to children for their moral enlistment)? Michael Hand has recently defended a foundationalist approach to answering this question and John White has responded by (a) criticizing…

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

Science.gov (United States)

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.

Hybrid Sterility Locus on Chromosome X Controls Meiotic Recombination Rate in Mouse.

Directory of Open Access Journals (Sweden)

Maria Balcova

2016-04-01

Full Text Available Meiotic recombination safeguards proper segregation of homologous chromosomes into gametes, affects genetic variation within species, and contributes to meiotic chromosome recognition, pairing and synapsis. The Prdm9 gene has a dual role, it controls meiotic recombination by determining the genomic position of crossover hotspots and, in infertile hybrids of house mouse subspecies Mus m. musculus (Mmm and Mus m. domesticus (Mmd, it further functions as the major hybrid sterility gene. In the latter role Prdm9 interacts with the hybrid sterility X 2 (Hstx2 genomic locus on Chromosome X (Chr X by a still unknown mechanism. Here we investigated the meiotic recombination rate at the genome-wide level and its possible relation to hybrid sterility. Using immunofluorescence microscopy we quantified the foci of MLH1 DNA mismatch repair protein, the cytological counterparts of reciprocal crossovers, in a panel of inter-subspecific chromosome substitution strains. Two autosomes, Chr 7 and Chr 11, significantly modified the meiotic recombination rate, yet the strongest modifier, designated meiotic recombination 1, Meir1, emerged in the 4.7 Mb Hstx2 genomic locus on Chr X. The male-limited transgressive effect of Meir1 on recombination rate parallels the male-limited transgressive role of Hstx2 in hybrid male sterility. Thus, both genetic factors, the Prdm9 gene and the Hstx2/Meir1 genomic locus, indicate a link between meiotic recombination and hybrid sterility. A strong female-specific modifier of meiotic recombination rate with the effect opposite to Meir1 was localized on Chr X, distally to Meir1. Mapping Meir1 to a narrow candidate interval on Chr X is an important first step towards positional cloning of the respective gene(s responsible for variation in the global recombination rate between closely related mouse subspecies.

Hybrid Sterility Locus on Chromosome X Controls Meiotic Recombination Rate in Mouse.

Science.gov (United States)

Balcova, Maria; Faltusova, Barbora; Gergelits, Vaclav; Bhattacharyya, Tanmoy; Mihola, Ondrej; Trachtulec, Zdenek; Knopf, Corinna; Fotopulosova, Vladana; Chvatalova, Irena; Gregorova, Sona; Forejt, Jiri

2016-04-01

Meiotic recombination safeguards proper segregation of homologous chromosomes into gametes, affects genetic variation within species, and contributes to meiotic chromosome recognition, pairing and synapsis. The Prdm9 gene has a dual role, it controls meiotic recombination by determining the genomic position of crossover hotspots and, in infertile hybrids of house mouse subspecies Mus m. musculus (Mmm) and Mus m. domesticus (Mmd), it further functions as the major hybrid sterility gene. In the latter role Prdm9 interacts with the hybrid sterility X 2 (Hstx2) genomic locus on Chromosome X (Chr X) by a still unknown mechanism. Here we investigated the meiotic recombination rate at the genome-wide level and its possible relation to hybrid sterility. Using immunofluorescence microscopy we quantified the foci of MLH1 DNA mismatch repair protein, the cytological counterparts of reciprocal crossovers, in a panel of inter-subspecific chromosome substitution strains. Two autosomes, Chr 7 and Chr 11, significantly modified the meiotic recombination rate, yet the strongest modifier, designated meiotic recombination 1, Meir1, emerged in the 4.7 Mb Hstx2 genomic locus on Chr X. The male-limited transgressive effect of Meir1 on recombination rate parallels the male-limited transgressive role of Hstx2 in hybrid male sterility. Thus, both genetic factors, the Prdm9 gene and the Hstx2/Meir1 genomic locus, indicate a link between meiotic recombination and hybrid sterility. A strong female-specific modifier of meiotic recombination rate with the effect opposite to Meir1 was localized on Chr X, distally to Meir1. Mapping Meir1 to a narrow candidate interval on Chr X is an important first step towards positional cloning of the respective gene(s) responsible for variation in the global recombination rate between closely related mouse subspecies.

Pendekatan Naratif dalam Konseling Rational Emotive Behavior Therapy (Rebt) untuk Mengelola Emosi

OpenAIRE

Purbaning Tyas, Prias Hayu

2015-01-01

The research aims to obtain an overview of the effectiveness of the narrative approach in counseling Rational Emotive Behavior Therapy (REBT) to manage emotions. The approach used in this study is a quantitative approach using a quasi-experimental methods. The study design used is one group pretest-posttest design using purposive sampling technique. The samples were 6 students who score low emotion management. The instrument used in the form of guidelines for the interview to express emotion ...

Auger recombination in sodium iodide

Science.gov (United States)

McAllister, Andrew; Kioupakis, Emmanouil; Åberg, Daniel; Schleife, André

2014-03-01

Scintillators are an important tool used to detect high energy radiation - both in the interest of national security and in medicine. However, scintillator detectors currently suffer from lower energy resolutions than expected from basic counting statistics. This has been attributed to non-proportional light yield compared to incoming radiation, but the specific mechanism for this non-proportionality has not been identified. Auger recombination is a non-radiative process that could be contributing to the non-proportionality of scintillating materials. Auger recombination comes in two types - direct and phonon-assisted. We have used first-principles calculations to study Auger recombination in sodium iodide, a well characterized scintillating material. Our findings indicate that phonon-assisted Auger recombination is stronger in sodium iodide than direct Auger recombination. Computational resources provided by LLNL and NERSC. Funding provided by NA-22.

Confucian Rationalism

Science.gov (United States)

Lam, Chi-Ming

2014-01-01

Nowadays, there is still a widely held view that the Chinese and Western modes of thought are quite distinct from each other. In particular, the Chinese mode of thought derived from Confucianism is considered as comparatively less rational than the Western one. In this article, I first argue that although the analogical mode of argumentation,…

Regulation of homologous recombination in eukaryotes

OpenAIRE

Heyer, Wolf-Dietrich; Ehmsen, Kirk T.; Liu, Jie

2010-01-01

Homologous recombination is required for accurate chromosome segregation during the first meiotic division and constitutes a key repair and tolerance pathway for complex DNA damage including DNA double-stranded breaks, interstrand crosslinks, and DNA gaps. In addition, recombination and replication are inextricably linked, as recombination recovers stalled and broken replication forks enabling the evolution of larger genomes/replicons. Defects in recombination lead to genomic instability and ...

Cognitive distance, absorptive capacity and group rationality: a simulation study.

Directory of Open Access Journals (Sweden)

Petru Lucian Curşeu

Full Text Available We report the results of a simulation study in which we explore the joint effect of group absorptive capacity (as the average individual rationality of the group members and cognitive distance (as the distance between the most rational group member and the rest of the group on the emergence of collective rationality in groups. We start from empirical results reported in the literature on group rationality as collective group level competence and use data on real-life groups of four and five to validate a mathematical model. We then use this mathematical model to predict group level scores from a variety of possible group configurations (varying both in cognitive distance and average individual rationality. Our results show that both group competence and cognitive distance are necessary conditions for emergent group rationality. Group configurations, in which the groups become more rational than the most rational group member, are groups scoring low on cognitive distance and scoring high on absorptive capacity.

Cognitive distance, absorptive capacity and group rationality: a simulation study.

Science.gov (United States)

Curşeu, Petru Lucian; Krehel, Oleh; Evers, Joep H M; Muntean, Adrian

2014-01-01

We report the results of a simulation study in which we explore the joint effect of group absorptive capacity (as the average individual rationality of the group members) and cognitive distance (as the distance between the most rational group member and the rest of the group) on the emergence of collective rationality in groups. We start from empirical results reported in the literature on group rationality as collective group level competence and use data on real-life groups of four and five to validate a mathematical model. We then use this mathematical model to predict group level scores from a variety of possible group configurations (varying both in cognitive distance and average individual rationality). Our results show that both group competence and cognitive distance are necessary conditions for emergent group rationality. Group configurations, in which the groups become more rational than the most rational group member, are groups scoring low on cognitive distance and scoring high on absorptive capacity.

Rational Design of Mixed-Metal Oxides for Chemical Looping Combustion of Coal via Coupled Computational-Experimental Studies

Energy Technology Data Exchange (ETDEWEB)

Mishra, Amit [North Carolina State Univ., Raleigh, NC (United States); Li, Fanxing [North Carolina State Univ., Raleigh, NC (United States); Santiso, Erik [North Carolina State Univ., Raleigh, NC (United States)

2017-09-18

Energy and global climate change are two grand challenges to the modern society. An urgent need exists for development of clean and efficient energy conversion processes. The chemical looping strategy, which utilizes regenerable oxygen carriers (OCs) to indirectly convert carbonaceous fuels via redox reactions, is considered to be one of the more promising approaches for CO2 capture by the U.S. Department of Energy (USDOE). To date, most long-term chemical looping operations were conducted using gaseous fuels, even though direct conversion of coal is more desirable from both economics and CO2 capture viewpoints. The main challenges for direct coal conversion reside in the stringent requirements on oxygen carrier performances. In addition, coal char and volatile compounds are more challenging to convert than gaseous fuels. A promising approach for direct conversion of coal is the so called chemical looping with oxygen uncoupling (CLOU) technique. In the CLOU process, a metal oxide that decomposes at the looping temperature, and releases oxygen to the gas phase is used as the OC. The overarching objective of this project was to discover the fundamental principles for rational design and optimization of oxygen carriers (OC) in coal chemical looping combustion (CLC) processes. It directly addresses Topic Area B of the funding opportunity announcement (FOA) in terms of “predictive description of the phase behavior and mechanical properties” of “mixed metal oxide” based OCs and rational development of new OC materials with superior functionality. This was achieved through studies exploring i) iron-containing mixed-oxide composites as oxygen carriers for CLOU, ii) Ca1-xAxMnO3-δ (A = Sr and Ba) as oxygen carriers for CLOU, iii) CaMn1-xBxO3-δ (B=Al, V, Fe, Co, and Ni) as oxygen carrier for CLOU and iv) vacancy creation energy in Mn-containing perovskites as an indicator chemical looping with oxygen uncoupling.

Emotions as a Vehicle for Rationality: Rational Decision Making Models Based on Emotion-Related Valuing and Hebbian Learning

NARCIS (Netherlands)

Treur, J.; Umair, M.

2015-01-01

In this paper an adaptive decision model based on predictive loops through feeling states is analysed from the perspective of rationality. Hebbian learning is considered for different types of connections in the decision model. To assess the extent of rationality, a measure is introduced reflecting

Extension of P-adic Exact Scientific Computational Library (ESCL) to Compute the Exponential of Rational Matrix

National Research Council Canada - National Science Library

Lu, Chao

2008-01-01

...) using p-adic arithmetic. New algorithms have been designed and implemented for matrix operations with rational numbers by representing numerator and denominator with arbitrary length integers, all integers and fractional...

Re-visions of rationality?

Science.gov (United States)

Newell, Ben R

2005-01-01

The appeal of simple algorithms that take account of both the constraints of human cognitive capacity and the structure of environments has been an enduring theme in cognitive science. A novel version of such a boundedly rational perspective views the mind as containing an 'adaptive toolbox' of specialized cognitive heuristics suited to different problems. Although intuitively appealing, when this version was proposed, empirical evidence for the use of such heuristics was scant. I argue that in the light of empirical studies carried out since then, it is time this 'vision of rationality' was revised. An alternative view based on integrative models rather than collections of heuristics is proposed.

Children's understanding of the costs and rewards underlying rational action.

Science.gov (United States)

Jara-Ettinger, Julian; Gweon, Hyowon; Tenenbaum, Joshua B; Schulz, Laura E

2015-07-01

Humans explain and predict other agents' behavior using mental state concepts, such as beliefs and desires. Computational and developmental evidence suggest that such inferences are enabled by a principle of rational action: the expectation that agents act efficiently, within situational constraints, to achieve their goals. Here we propose that the expectation of rational action is instantiated by a naïve utility calculus sensitive to both agent-constant and agent-specific aspects of costs and rewards associated with actions. In four experiments, we show that, given an agent's choices, children (range: 5-6 year olds; N=96) can infer unobservable aspects of costs (differences in agents' competence) from information about subjective differences in rewards (differences in agents' preferences) and vice versa. Moreover, children can design informative experiments on both objects and agents to infer unobservable constraints on agents' actions. Copyright © 2015 Elsevier B.V. All rights reserved.

Rationing medical education.

African Journals Online (AJOL)

This paper discussed the pros and cons of the application of rationing to medical education and the different ... Even though some stakeholders in medical education might be taken aback at .... Walsh K. Online educational tools to improve the.

Rationality, perception, and the all-seeing eye.

Science.gov (United States)

Felin, Teppo; Koenderink, Jan; Krueger, Joachim I

2017-08-01

Seeing-perception and vision-is implicitly the fundamental building block of the literature on rationality and cognition. Herbert Simon and Daniel Kahneman's arguments against the omniscience of economic agents-and the concept of bounded rationality-depend critically on a particular view of the nature of perception and vision. We propose that this framework of rationality merely replaces economic omniscience with perceptual omniscience. We show how the cognitive and social sciences feature a pervasive but problematic meta-assumption that is characterized by an "all-seeing eye." We raise concerns about this assumption and discuss different ways in which the all-seeing eye manifests itself in existing research on (bounded) rationality. We first consider the centrality of vision and perception in Simon's pioneering work. We then point to Kahneman's work-particularly his article "Maps of Bounded Rationality"-to illustrate the pervasiveness of an all-seeing view of perception, as manifested in the extensive use of visual examples and illusions. Similar assumptions about perception can be found across a large literature in the cognitive sciences. The central problem is the present emphasis on inverse optics-the objective nature of objects and environments, e.g., size, contrast, and color. This framework ignores the nature of the organism and perceiver. We argue instead that reality is constructed and expressed, and we discuss the species-specificity of perception, as well as perception as a user interface. We draw on vision science as well as the arts to develop an alternative understanding of rationality in the cognitive and social sciences. We conclude with a discussion of the implications of our arguments for the rationality and decision-making literature in cognitive psychology and behavioral economics, along with suggesting some ways forward.

Recombinant Newcastle disease virus-vectored vaccines against human and animal infectious diseases.

Science.gov (United States)

Duan, Zhiqiang; Xu, Houqiang; Ji, Xinqin; Zhao, Jiafu

2015-01-01

Recent advances in recombinant genetic engineering techniques have brought forward a leap in designing new vaccines in modern medicine. One attractive strategy is the application of reverse genetics technology to make recombinant Newcastle disease virus (rNDV) deliver protective antigens of pathogens. In recent years, numerous studies have demonstrated that rNDV-vectored vaccines can induce quicker and better humoral and mucosal immune responses than conventional vaccines and are protective against pathogen challenges. With deeper understanding of NDV molecular biology, it is feasible to develop gene-modified rNDV vaccines accompanied by good safety, high efficacy, low toxicity and better immunogenicity. This review summarizes the development of reverse genetics technology in using NDV as a promising vaccine vector to design new vaccines for human and animal use.

Towards a classification of rational Hopf algebras

International Nuclear Information System (INIS)

Fuchs, J.; Ganchev, A.; Vecsernyes, P.

1994-02-01

Rational Hopf algebras, i.e. certain quasitriangular weak quasi-Hopf *-algebras, are expected to describe the quantum symmetry of rational field theories. In this paper methods are developed which allow for a classification of all rational Hopf algebras that are compatible with some prescribed set of fusion rules. The algebras are parametrized by the solutions of the square, pentagon and hexagon identities. As examples, we classify all solutions for fusion rules with not more than three sectors, as well as for the level three affine A 1 (1) fusion rules. We also establish several general properties of rational Hopf algebras and present a graphical description of the coassociator in terms of labelled tetrahedra. The latter construction allows to make contact with conformal field theory fusing matrices and with invariants of three-manifolds and topological lattice field theory. (orig.)

Bounded rational choice behaviour: applications in transport

DEFF Research Database (Denmark)

Jensen, Anders Fjendbo

2016-01-01

Even though the theory of rational behaviour has been challenged for almost 100 years, the dominant approach within the field of transport has been based upon the assumptions of neoclassical economics that we live in a world of rational decision makers who always have perfect knowledge and aim...... rational choice behaviour focuses on how the latter approach can be seriously taken into account within transport applications. As the editors discuss in the introduction, a true optimal choice can only be made if an individual has full and perfect information of all relevant attributes in his/her choice...... set. An individual is said to demonstrate bounded rational behaviour if he/she does not systematically consider all attributes deemed relevant for the decision problem at hand, does not consider all choice options and/or does not choose the best choice alternative. Such simplified representation...

Economic Rationality in the Ultimatum Game

Directory of Open Access Journals (Sweden)

Jan Fiala

2017-03-01

Full Text Available Rigorous application of experimental methodology to the interdisciplinary research of economic decision making is the main purpose of our work. In this paper, we introduce the main decisionmaking theories and outline economic rationality. We explain why we find it useful to discriminate between the “irrational” and “non-rational” components of decision making. We offer an oriented interdisciplinary point of view on economic rationality. In the applied section, we describe the main features of the Ultimatum game and summarize the up-to-date theories explaining the non-rational course of the game. We discuss in detail the reported relations between the nominal value of the stakes and the distribution of the offers and responses. We introduce the blinded, randomized Ultimatum game experiment that we conducted in our laboratory. We stress the importance of anonymity of the study subjects and the difference in salience of a factual reward against a  hypothetical reward. We present the results of our study, showing that a  duly chosen non-monetary reward, directly inconvertible into money, leads to a different offer distribution in the Ultimatum game without the necessity to invest excessive sums of money in the rewards. We compare our results to research published by other authors. According to our theory, the rational, non-rational and irrational components contribute to the decision making in Ultimatum differently depending on the different reward stakes.

Recombination coefficients in extrinsic n-InSb

International Nuclear Information System (INIS)

Schneider, W.; Groh, H.; Huebner, K.

1976-01-01

The bulk recombination coefficients for linear recombination via recombination centers as well as for direct recombination have been determined measuring the conductivity decay after two-photon absorption with a CO 2 laser. The Suhl effect was applied to measure the surface recombination velocity. The corresponding literature is discussed and compared with our results. We conclude that two different kinds of recombination centers are possible in n-InSb, with energy levels (0.1-0.12)eV above the valence band, or (0.14-0.2)eV respectively. (orig.) [de

Structural Basis for Escape of Human Astrovirus from Antibody Neutralization: Broad Implications for Rational Vaccine Design

Energy Technology Data Exchange (ETDEWEB)

Bogdanoff, Walter A.; Perez, Edmundo I.; López, Tomás; Arias, Carlos F.; DuBois, Rebecca M. (UNAM-Mexico); (UCSC)

2017-10-25

a single amino acid mutation induces a structural change in a loop that is responsible for antibody binding. Our findings reveal how viruses can escape antibody neutralization and provide insight for the rational design of vaccines to elicit diverse antibodies that provide broader protection from infection.