Imagine-Self Perspective-Taking and Rational Self-Interested Behavior in a Simple Experimental Normal-Form Game

PubMed Central

Karbowski, Adam; Ramsza, Michał

2017-01-01

The purpose of this study is to explore the link between imagine-self perspective-taking and rational self-interested behavior in experimental normal-form games. Drawing on the concept of sympathy developed by Adam Smith and further literature on perspective-taking in games, we hypothesize that introduction of imagine-self perspective-taking by decision-makers promotes rational self-interested behavior in a simple experimental normal-form game. In our study, we examined behavior of 404 undergraduate students in the two-person game, in which the participant can suffer a monetary loss only if she plays her Nash equilibrium strategy and the opponent plays her dominated strategy. Results suggest that the threat of suffering monetary losses effectively discourages the participants from choosing Nash equilibrium strategy. In general, players may take into account that opponents choose dominated strategies due to specific not self-interested motivations or errors. However, adopting imagine-self perspective by the participants leads to more Nash equilibrium choices, perhaps by alleviating participants’ attributions of susceptibility to errors or non-self-interested motivation to the opponents. PMID:28955276

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

NASA Astrophysics Data System (ADS)

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

2015-11-01

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

Toward a rational understanding of migraine trigger factors.

PubMed

Martin, V T; Behbehani, M M

2001-07-01

The typical migraine patient is exposed to a myriad of migraine triggers on a daily basis. These triggers potentially can act at various sites within the cerebral vasculature and the central nervous system to promote the development of migraine headache. The challenge to the physician is in the identification and avoidance of migraine trigger factors within patients suffering from migraine headache. Only through a rational approach to migraine trigger factors can physicians develop an appropriate treatment strategy for migraine patients.

Working Memory Strategies during Rational Number Magnitude Processing

ERIC Educational Resources Information Center

Hurst, Michelle; Cordes, Sara

2017-01-01

Rational number understanding is a critical building block for success in more advanced mathematics; however, how rational number magnitudes are conceptualized is not fully understood. In the current study, we used a dual-task working memory (WM) interference paradigm to investigate the dominant type of strategy (i.e., requiring verbal WM…

The Integration of Extrarational and Rational Learning Processes: Moving Towards the Whole Learner.

ERIC Educational Resources Information Center

Puk, Tom

1996-01-01

Discusses the dichotomy between rational and nonrational learning processes, arguing for an integration of both. Reviews information processing theory and related learning strategies. Presents a model instructional strategy that fully integrates rational and nonrational processes. Describes implications for teaching and learning of the learning…

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

PubMed

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

2016-05-11

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

The Different Faces of Racism in Higher Education.

ERIC Educational Resources Information Center

D'Andrea, Michael; Daniels, Judy

1994-01-01

A framework for examining racism in higher education is outlined. It distinguishes several stages of racist attitude: affective-impulsive, dualistic rational, libertarian, principled, and principled-activist. These stages of cognitive development are suggested as a model for planning intervention strategies. Some specific strategies are described.…

Dual kinase-bromodomain inhibitors for rationally designed polypharmacology

PubMed Central

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

2014-01-01

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

Rational adaptation under task and processing constraints: implications for testing theories of cognition and action.

PubMed

Howes, Andrew; Lewis, Richard L; Vera, Alonso

2009-10-01

The authors assume that individuals adapt rationally to a utility function given constraints imposed by their cognitive architecture and the local task environment. This assumption underlies a new approach to modeling and understanding cognition-cognitively bounded rational analysis-that sharpens the predictive acuity of general, integrated theories of cognition and action. Such theories provide the necessary computational means to explain the flexible nature of human behavior but in doing so introduce extreme degrees of freedom in accounting for data. The new approach narrows the space of predicted behaviors through analysis of the payoff achieved by alternative strategies, rather than through fitting strategies and theoretical parameters to data. It extends and complements established approaches, including computational cognitive architectures, rational analysis, optimal motor control, bounded rationality, and signal detection theory. The authors illustrate the approach with a reanalysis of an existing account of psychological refractory period (PRP) dual-task performance and the development and analysis of a new theory of ordered dual-task responses. These analyses yield several novel results, including a new understanding of the role of strategic variation in existing accounts of PRP and the first predictive, quantitative account showing how the details of ordered dual-task phenomena emerge from the rational control of a cognitive system subject to the combined constraints of internal variance, motor interference, and a response selection bottleneck.

Effects of Computer-Assisted Instruction in Using Formal Decision-Making Strategies to Choose a College Major.

ERIC Educational Resources Information Center

Mau, Wei-Cheng; Jepsen, David A.

1992-01-01

Compared decision-making strategies and college major choice among 113 first-year students assigned to Elimination by Aspects Strategy (EBA), Subjective Expected Utility Strategy (SEU), and control groups. "Rational" EBA students scored significantly higher on choice certainty; lower on choice anxiety and career indecision than "rational"…

Rational design of high-yield and superior-quality rice.

PubMed

Zeng, Dali; Tian, Zhixi; Rao, Yuchun; Dong, Guojun; Yang, Yaolong; Huang, Lichao; Leng, Yujia; Xu, Jie; Sun, Chuan; Zhang, Guangheng; Hu, Jiang; Zhu, Li; Gao, Zhenyu; Hu, Xingming; Guo, Longbiao; Xiong, Guosheng; Wang, Yonghong; Li, Jiayang; Qian, Qian

2017-03-20

Rice (Oryza sativa L.) is a staple food for more than half of the world's population. To meet the ever-increasing demand for food, because of population growth and improved living standards, world rice production needs to double by 2030 1 . The development of new elite rice varieties with high yield and superior quality is challenging for traditional breeding approaches, and new strategies need to be developed. Here, we report the successful development of new elite varieties by pyramiding major genes that significantly contribute to grain quality and yield from three parents over five years. The new varieties exhibit higher yield potential and better grain quality than their parental varieties and the China's leading super-hybrid rice, Liang-you-pai-jiu (LYP9 or Pei-ai 64S/93-11). Our results demonstrate that rational design is a powerful strategy for meeting the challenges of future crop breeding, particularly in pyramiding multiple complex traits.

The Relation between Career Decision-Making Strategies and Person-Job Fit: A Study of Job Changers

ERIC Educational Resources Information Center

Singh, Romila; Greenhaus, Jeffrey H.

2004-01-01

This study examined relations between three career decision-making strategies (rational, intuitive, and dependent) and person--job fit among 361 professionals who had recently changed jobs. We found that the relation between each decision-making strategy and fit was contingent upon the concurrent use of other strategies. A rational strategy…

Learning strategies during clerkships and their effects on clinical performance.

PubMed

van Lohuizen, M T; Kuks, J B M; van Hell, E A; Raat, A N; Cohen-Schotanus, J

2009-11-01

Previous research revealed relationships between learning strategies and knowledge acquisition. During clerkships, however, students' focus widens beyond mere knowledge acquisition as they further develop overall competence. This shift in focus can influence learning strategy use. We explored which learning strategies were used during clerkships and their relationship to clinical performance. Participants were 113 (78%) clerks at the university hospital or one of six affiliated hospitals. Learning strategies were assessed using the 'Approaches to Learning at Work Questionnaire' (deep, surface-rational and surface-disorganised learning). Clinical performance was calculated by taking the mean of clinical assessment marks. The relationship between learning strategies and clinical performance was explored using regression analysis. Most students (89%) did not clearly prefer a single learning strategy. No relationship was found between learning strategies and clinical performance. Since overall competence comprises integration of knowledge, skills and professional behaviour, we assume that students without a clear preference use more than one learning strategy. Finding no relationship between learning strategies and clinical performance reflects the complexity of clinical learning. Depending on circumstances it may be important to obtain relevant information quickly (surface-rational) or understand material thoroughly (deep). In future research we will examine when and why students use different learning strategies.

Randomness in the network inhibits cooperation based on the bounded rational collective altruistic decision

NASA Astrophysics Data System (ADS)

Ohdaira, Tetsushi

2014-07-01

Previous studies discussing cooperation employ the best decision that every player knows all information regarding the payoff matrix and selects the strategy of the highest payoff. Therefore, they do not discuss cooperation based on the altruistic decision with limited information (bounded rational altruistic decision). In addition, they do not cover the case where every player can submit his/her strategy several times in a match of the game. This paper is based on Ohdaira's reconsideration of the bounded rational altruistic decision, and also employs the framework of the prisoner's dilemma game (PDG) with sequential strategy. The distinction between this study and the Ohdaira's reconsideration is that the former covers the model of multiple groups, but the latter deals with the model of only two groups. Ohdaira's reconsideration shows that the bounded rational altruistic decision facilitates much more cooperation in the PDG with sequential strategy than Ohdaira and Terano's bounded rational second-best decision does. However, the detail of cooperation of multiple groups based on the bounded rational altruistic decision has not been resolved yet. This study, therefore, shows how randomness in the network composed of multiple groups affects the increase of the average frequency of mutual cooperation (cooperation between groups) based on the bounded rational altruistic decision of multiple groups. We also discuss the results of the model in comparison with related studies which employ the best decision.

Ecological Rationality: A Framework for Understanding and Aiding the Aging Decision Maker

PubMed Central

Mata, Rui; Pachur, Thorsten; von Helversen, Bettina; Hertwig, Ralph; Rieskamp, Jörg; Schooler, Lael

2012-01-01

The notion of ecological rationality sees human rationality as the result of the adaptive fit between the human mind and the environment. Ecological rationality focuses the study of decision making on two key questions: First, what are the environmental regularities to which people’s decision strategies are matched, and how frequently do these regularities occur in natural environments? Second, how well can people adapt their use of specific strategies to particular environmental regularities? Research on aging suggests a number of changes in cognitive function, for instance, deficits in learning and memory that may impact decision-making skills. However, it has been shown that simple strategies can work well in many natural environments, which suggests that age-related deficits in strategy use may not necessarily translate into reduced decision quality. Consequently, we argue that predictions about the impact of aging on decision performance depend not only on how aging affects decision-relevant capacities but also on the decision environment in which decisions are made. In sum, we propose that the concept of the ecological rationality is crucial to understanding and aiding the aging decision maker. PMID:22347843

Ecological rationality: a framework for understanding and aiding the aging decision maker.

PubMed

Mata, Rui; Pachur, Thorsten; von Helversen, Bettina; Hertwig, Ralph; Rieskamp, Jörg; Schooler, Lael

2012-01-01

The notion of ecological rationality sees human rationality as the result of the adaptive fit between the human mind and the environment. Ecological rationality focuses the study of decision making on two key questions: First, what are the environmental regularities to which people's decision strategies are matched, and how frequently do these regularities occur in natural environments? Second, how well can people adapt their use of specific strategies to particular environmental regularities? Research on aging suggests a number of changes in cognitive function, for instance, deficits in learning and memory that may impact decision-making skills. However, it has been shown that simple strategies can work well in many natural environments, which suggests that age-related deficits in strategy use may not necessarily translate into reduced decision quality. Consequently, we argue that predictions about the impact of aging on decision performance depend not only on how aging affects decision-relevant capacities but also on the decision environment in which decisions are made. In sum, we propose that the concept of the ecological rationality is crucial to understanding and aiding the aging decision maker.

Dynamic route guidance strategy in a two-route pedestrian-vehicle mixed traffic flow system

NASA Astrophysics Data System (ADS)

Liu, Mianfang; Xiong, Shengwu; Li, Bixiang

2016-05-01

With the rapid development of transportation, traffic questions have become the major issue for social, economic and environmental aspects. Especially, during serious emergencies, it is very important to alleviate road traffic congestion and improve the efficiency of evacuation to reduce casualties, and addressing these problems has been a major task for the agencies responsible in recent decades. Advanced road guidance strategies have been developed for homogeneous traffic flows, or to reduce traffic congestion and enhance the road capacity in a symmetric two-route scenario. However, feedback strategies have rarely been considered for pedestrian-vehicle mixed traffic flows with variable velocities and sizes in an asymmetric multi-route traffic system, which is a common phenomenon in many developing countries. In this study, we propose a weighted road occupancy feedback strategy (WROFS) for pedestrian-vehicle mixed traffic flows, which considers the system equilibrium to ease traffic congestion. In order to more realistic simulating the behavior of mixed traffic objects, the paper adopted a refined and dynamic cellular automaton model (RDPV_CA model) as the update mechanism for pedestrian-vehicle mixed traffic flow. Moreover, a bounded rational threshold control was introduced into the feedback strategy to avoid some negative effect of delayed information and reduce. Based on comparisons with the two previously proposed strategies, the simulation results obtained in a pedestrian-vehicle traffic flow scenario demonstrated that the proposed strategy with a bounded rational threshold was more effective and system equilibrium, system stability were reached.

Influence of individual rationality on continuous double auction markets with networked traders

NASA Astrophysics Data System (ADS)

Zhang, Junhuan

2018-04-01

This paper investigates the influence of individual rationality of buyers and sellers on continuous double auction market outcomes in terms of the proportion of boundedly-rational buyers and sellers. The individual rationality is discussed in a social network artificial stock market model by embedding network formation and information set. Traders automatically select the most profitable trading strategy based on individual and social learning of the profits and trading strategies of themselves and their neighbors, and submit orders to markets. The results show that (i) a higher proportion of boundedly-rational sellers induces a higher market price, higher sellers' profits and a higher market efficiency; (ii) a higher proportion of boundedly-rational sellers induces a lower number of trades and lower buyers' profits; (iii) a higher proportion of boundedly-rational buyers induces a lower market price, a lower number of trades, and lower sellers' profits; (iv) a higher proportion of boundedly-rational buyers induces higher buyers' profits and a higher market efficiency.

Generation and development of RNA ligase ribozymes with modular architecture through "design and selection".

PubMed

Fujita, Yuki; Ishikawa, Junya; Furuta, Hiroyuki; Ikawa, Yoshiya

2010-08-26

In vitro selection with long random RNA libraries has been used as a powerful method to generate novel functional RNAs, although it often requires laborious structural analysis of isolated RNA molecules. Rational RNA design is an attractive alternative to avoid this laborious step, but rational design of catalytic modules is still a challenging task. A hybrid strategy of in vitro selection and rational design has been proposed. With this strategy termed "design and selection," new ribozymes can be generated through installation of catalytic modules onto RNA scaffolds with defined 3D structures. This approach, the concept of which was inspired by the modular architecture of naturally occurring ribozymes, allows prediction of the overall architectures of the resulting ribozymes, and the structural modularity of the resulting ribozymes allows modification of their structures and functions. In this review, we summarize the design, generation, properties, and engineering of four classes of ligase ribozyme generated by design and selection.

Reasoning strategies with rational numbers revealed by eye tracking.

PubMed

Plummer, Patrick; DeWolf, Melissa; Bassok, Miriam; Gordon, Peter C; Holyoak, Keith J

2017-07-01

Recent research has begun to investigate the impact of different formats for rational numbers on the processes by which people make relational judgments about quantitative relations. DeWolf, Bassok, and Holyoak (Journal of Experimental Psychology: General, 144(1), 127-150, 2015) found that accuracy on a relation identification task was highest when fractions were presented with countable sets, whereas accuracy was relatively low for all conditions where decimals were presented. However, it is unclear what processing strategies underlie these disparities in accuracy. We report an experiment that used eye-tracking methods to externalize the strategies that are evoked by different types of rational numbers for different types of quantities (discrete vs. continuous). Results showed that eye-movement behavior during the task was jointly determined by image and number format. Discrete images elicited a counting strategy for both fractions and decimals, but this strategy led to higher accuracy only for fractions. Continuous images encouraged magnitude estimation and comparison, but to a greater degree for decimals than fractions. This strategy led to decreased accuracy for both number formats. By analyzing participants' eye movements when they viewed a relational context and made decisions, we were able to obtain an externalized representation of the strategic choices evoked by different ontological types of entities and different types of rational numbers. Our findings using eye-tracking measures enable us to go beyond previous studies based on accuracy data alone, demonstrating that quantitative properties of images and the different formats for rational numbers jointly influence strategies that generate eye-movement behavior.

Rational Combinations of Targeted Agents in AML

PubMed Central

Bose, Prithviraj; Grant, Steven

2015-01-01

Despite modest improvements in survival over the last several decades, the treatment of AML continues to present a formidable challenge. Most patients are elderly, and these individuals, as well as those with secondary, therapy-related, or relapsed/refractory AML, are particularly difficult to treat, owing to both aggressive disease biology and the high toxicity of current chemotherapeutic regimens. It has become increasingly apparent in recent years that coordinated interruption of cooperative survival signaling pathways in malignant cells is necessary for optimal therapeutic results. The modest efficacy of monotherapy with both cytotoxic and targeted agents in AML testifies to this. As the complex biology of AML continues to be elucidated, many “synthetic lethal” strategies involving rational combinations of targeted agents have been developed. Unfortunately, relatively few of these have been tested clinically, although there is growing interest in this area. In this article, the preclinical and, where available, clinical data on some of the most promising rational combinations of targeted agents in AML are summarized. While new molecules should continue to be combined with conventional genotoxic drugs of proven efficacy, there is perhaps a need to rethink traditional philosophies of clinical trial development and regulatory approval with a focus on mechanism-based, synergistic strategies. PMID:26113989

Co-action provides rational basis for the evolutionary success of Pavlovian strategies

NASA Astrophysics Data System (ADS)

Sasidevan, V.; Sinha, Sitabhra

2016-08-01

Strategies incorporating direct reciprocity, e.g., Tit-for-Tat and Pavlov, have been shown to be successful for playing the Iterated Prisoners Dilemma (IPD), a paradigmatic problem for studying the evolution of cooperation among non-kin individuals. However it is an open question whether such reciprocal strategies can emerge as the rational outcome of repeated interactions between selfish agents. Here we show that adopting a co-action perspective, which takes into account the symmetry between agents - a relevant consideration in biological and social contexts - naturally leads to such a strategy. For a 2-player IPD, we show that the co-action solution corresponds to the Pavlov strategy, thereby providing a rational basis for it. For an IPD involving many players, an instance of the Public Goods game where cooperation is generally considered to be harder to achieve, we show that the cooperators always outnumber defectors in the co-action equilibrium. This can be seen as a generalization of Pavlov to contests involving many players. In general, repeated interactions allow rational agents to become aware of the inherent symmetry of their situation, enabling them to achieve robust cooperation through co-action strategies - which, in the case of IPD, is a reciprocal Pavlovian one.

Identifying optimum performance trade-offs using a cognitively bounded rational analysis model of discretionary task interleaving.

PubMed

Janssen, Christian P; Brumby, Duncan P; Dowell, John; Chater, Nick; Howes, Andrew

2011-01-01

We report the results of a dual-task study in which participants performed a tracking and typing task under various experimental conditions. An objective payoff function was used to provide explicit feedback on how participants should trade off performance between the tasks. Results show that participants' dual-task interleaving strategy was sensitive to changes in the difficulty of the tracking task and resulted in differences in overall task performance. To test the hypothesis that people select strategies that maximize payoff, a Cognitively Bounded Rational Analysis model was developed. This analysis evaluated a variety of dual-task interleaving strategies to identify the optimal strategy for maximizing payoff in each condition. The model predicts that the region of optimum performance is different between experimental conditions. The correspondence between human data and the prediction of the optimal strategy is found to be remarkably high across a number of performance measures. This suggests that participants were honing their behavior to maximize payoff. Limitations are discussed. Copyright © 2011 Cognitive Science Society, Inc.

Departures from sensible play in computer blackjack.

PubMed

Chau, A W; Phillips, J G; Von Baggo, K L

2000-10-01

Gambling has been viewed as irrational, and even though blackjack offers rational strategies (i.e., Basic [E. Thorp, 1966] and card counting), people exhibit departures from rationality (e.g., "Never Bust" strategies). To determine whether departures from rational behavior reflect ignorance or fatigue, university students were provided with on-line Basic advice while playing a simplified computer blackjack. Although the on-line advice initially affected the totals these players sat on, it was eventually discarded for higher risk strategies. Irrational play did not reflect ignorance or fatigue and was not necessarily conservative. Real fluctuations of odds in blackjack may lead to situations in which Basic is not perceived by players as effective. Because Basic is not a personalized strategy, it seems less likely to be maintained in the face of losses. Players were more optimistic that they might win when utilizing their personalized strategies.

Rational design of gene-based vaccines.

PubMed

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.

Prevalence and Determinants of Physician Bedside Rationing

PubMed Central

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

2006-01-01

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

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

PubMed

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

2016-01-01

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

The Special Education Teacher as an Instructional Designer. Rational, Content, and Strategy for an Innovative Individualized Course on Instructional Design in Special Education. Working Paper 9.14.

ERIC Educational Resources Information Center

Thiagarajan, Sivasailam

Provided are the rationale, content and strategy for an introductory course in instructional design for special education teachers. The teacher's need for varied competencies in instructional design, management and interaction are discussed. It is recommended that teacher training include development of such design skills as task analysis, learner…

Developing a novel therapeutic strategy targeting Kallikrein-4 to inhibit prostate cancer growth and metastasis

DTIC Science & Technology

Kallikrein-related peptidase 4 (KLK4) is a rational therapeutic target for prostate cancer (PCa) as it is up-regulated in both localised and bone ...in PCa homing to bone . We therefore hypothesize that blockade of KLK4 activity will inhibit PCa growth and prevent metastasis to secondary sites like... bone . This project aims to develop a novel therapeutic strategy targeting KLK4 specifically in PCa. KLK4 siRNA is incorporated into a novel polymeric

Communication strategies in cosmetic surgery websites: an application of Taylor's six-segment message strategy wheel.

PubMed

Ahn, Ho-Young Anthony; Wu, Lei; Taylor, Ronald E

2013-01-01

Using Taylor's six-segment message strategy wheel as a theoretical framework, this study examines the communication approach (transmission or ritual) and message strategy (ego, social, sensory, routine, acute need, or ration) of cosmetic surgery websites. A content analysis revealed a fairly even division between transmission and ritual approaches. Ration strategy was the exclusive strategy in the websites adopting a transmission approach. No routine or acute need strategies were observed. Websites incorporating the ritual approach used ego, social, and sensory strategies. Human female models and natural objects were incorporated to deliver emotional persuasion. Implications for cosmetic surgery web marketers are discussed.

Developing Real Estate: A Rational Plan for Capitalizing on a Valuable Resource.

ERIC Educational Resources Information Center

Hughes, K. Scott; And Others

1991-01-01

The second part of a two-part article addresses four key issues for higher education administrators to consider as they investigate real estate opportunities. They are (1) market feasibility; (2) development strategy; (3) financing; and (4) governance. Guidelines for innovative real estate projects even during the potentially difficult early 1990s…

Economic impact of storage and handling regulations on retail fertilizer and pesticide firms

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

Akridge, J.T.; Rogers, D.S.

1994-12-31

A budgeting model was developed to estimate the cost of retailing dry bulk fertilizer, liquid bulk fertilizer, anhydrous ammonia, and pesticides for three sizes of facilities. Estimates were obtained of the cost to upgrade each of the model plants to comply with Indiana`s recently enacted regulations on the handling and storage of fertilizers and pesticides. In addition, various strategies (increasing price and increasing volume) that dealers might employ to rationalize these investments were assessed. Results suggest that there are significant scale economies associated with the regulations and that smaller plants will have a more difficult time rationalizing the investment thanmore » larger plants. Dealers will need to consider a range of strategies to offset the increase in annual operating costs resulting from these environmental investments.« less

Therapeutic vaccines in HBV: lessons from HCV.

PubMed

Barnes, Eleanor

2015-02-01

Currently, millions of people infected with hepatitis B virus (HBV) are committed to decades of treatment with anti-viral therapy to control viral replication. However, new tools for immunotherapy that include both viral vectors and molecular checkpoint inhibitors are now available. This has led to a resurgence of interest in new strategies to develop immunotherapeutic strategies with the aim of inducing HBeAg seroconversion--an end-point that has been associated with a decrease in the rates of disease progression. Ultimately, a true cure will involve the elimination of covalently closed circular DNA which presents a greater challenge for immunotherapy. In this manuscript, I describe the development of immunotherapeutic strategies for HBV that are approaching or currently in clinical studies, and draw on observations of T cell function in natural infection supported by recent animal studies that may lead to additional rational vaccine strategies using checkpoint inhibitors. I also draw on our recent experience in developing potent vaccines for HCV prophylaxis based on simian adenoviral and MVA vectors used in prime-boost strategies in both healthy volunteers and HCV infected patients. I have shown that the induction of T cell immune responses is markedly attenuated when administered to people with persistent HCV viremia. These studies and recently published animal studies using the woodchuck model suggest that potent vaccines based on DNA or adenoviral vectored vaccination represent a rational way forward. However, combining these with drugs to suppress viral replication, alongside checkpoint inhibitors may be required to induce long-term immune control.

Using Bar Representations as a Model for Connecting Concepts of Rational Number.

ERIC Educational Resources Information Center

Middleton, James A.; van den Heuvel-Panhuizen, Marja; Shew, Julia A.

1998-01-01

Examines bar models as graphical representations of rational numbers and presents related real life problems. Concludes that, through pairing the fraction bars with ratio tables and other ways of teaching numbers, numeric strategies become connected with visual strategies that allow students with diverse ways of thinking to share their…

Rationality alters the rank between peer punishment and social exclusion

NASA Astrophysics Data System (ADS)

Sui, Xiukai; Wu, Bin; Wang, Long

2018-02-01

Peer punishment and social exclusion are two ways to punish free-riders. Previous work usually focuses on how their presence, either peer punishment or social exclusion, shapes the evolution of cooperation. Little attention has been given to which of these two strategies is favored by natural selection when they are both present. Here we investigate how rationality alters the ranking of these two strategies. Under weak rationality, for compulsory public goods games, peer punishment has an evolutionary advantage over social exclusion if the efficiency of punishment or the cost of exclusion is high. Furthermore, this rank is preserved for voluntary public goods games where loners are involved. Under strong rationality, however, peer punishment cannot prevail over social exclusion for both compulsory and voluntary public goods games. This indicates that rationality greatly alters the rank between peer punishment and social exclusion. Moreover, we find that this ranking is sensitive to the rationality. Our work thus gives an insight into how different types of punishment evolve.

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

PubMed

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

2011-10-01

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

Microbial Enzymes: Tools for Biotechnological Processes

PubMed Central

Adrio, Jose L.; Demain, Arnold L.

2014-01-01

Microbial enzymes are of great importance in the development of industrial bioprocesses. Current applications are focused on many different markets including pulp and paper, leather, detergents and textiles, pharmaceuticals, chemical, food and beverages, biofuels, animal feed and personal care, among others. Today there is a need for new, improved or/and more versatile enzymes in order to develop more novel, sustainable and economically competitive production processes. Microbial diversity and modern molecular techniques, such as metagenomics and genomics, are being used to discover new microbial enzymes whose catalytic properties can be improved/modified by different strategies based on rational, semi-rational and random directed evolution. Most industrial enzymes are recombinant forms produced in bacteria and fungi. PMID:24970208

Imagination and the Pursuit of a Rational Rhetoric.

ERIC Educational Resources Information Center

Foster, David E.

The works of certain rhetorical thinkers contain strategies directed at achieving assent or cooperation. Such writings demonstrate means by which readers' rational responses can be deliberately challenged and disrupted. While people often cite Aristotle's maxim "Man is a rational animal," critics have asserted that the statement…

A response-time approach to comparing generalized rational and take-the-best models of decision making.

PubMed

Bergert, F Bryan; Nosofsky, Robert M

2007-01-01

The authors develop and test generalized versions of take-the-best (TTB) and rational (RAT) models of multiattribute paired-comparison inference. The generalized models make allowances for subjective attribute weighting, probabilistic orders of attribute inspection, and noisy decision making. A key new test involves a response-time (RT) approach. TTB predicts that RT is determined solely by the expected time required to locate the 1st discriminating attribute, whereas RAT predicts that RT is determined by the difference in summed evidence between the 2 alternatives. Critical test pairs are used that partially decouple these 2 factors. Under conditions in which ideal observer TTB and RAT strategies yield equivalent decisions, both the RT results and the estimated attribute weights suggest that the vast majority of subjects adopted the generalized TTB strategy. The RT approach is also validated in an experimental condition in which use of a RAT strategy is essentially forced upon subjects. (c) 2007 APA, all rights reserved.

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

PubMed

Wilson, Corey J

2015-01-01

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

Establishing rational networking using the DL04 quantum secure direct communication protocol

NASA Astrophysics Data System (ADS)

Qin, Huawang; Tang, Wallace K. S.; Tso, Raylin

2018-06-01

The first rational quantum secure direct communication scheme is proposed, in which we use the game theory with incomplete information to model the rational behavior of the participant, and give the strategy space and utility function. The rational participant can get his maximal utility when he performs the protocol faithfully, and then the Nash equilibrium of the protocol can be achieved. Compared to the traditional schemes, our scheme will be more practical in the presence of rational participant.

The Rational-Reality Based Approach to Treating the Criminal Child Abuser.

ERIC Educational Resources Information Center

Cox, Steven G.

1979-01-01

This appraoch to treating child abusers incorporates the philosophies of Rational Behavior Training and Reality Therapy into a therapeutic strategy that helps clients to learn skills in making rational decisions that can aid them in living harmoniously within the family structure. Five specific techniques are presented. (Author)

A "Mindful Rational Living" Approach for Addressing HIV in the School Setting

ERIC Educational Resources Information Center

Chenneville, Tiffany; St. John Walsh, Audra

2016-01-01

This paper describes a "mindful rational living" approach, which incorporates mindfulness techniques with rational emotive behavioral therapy strategies for addressing HIV in the school setting. The utility of this approach for attending to the physical, mental, and psychosocial aspects of school-based HIV prevention and treatment will…

Differences in Multitask Resource Reallocation After Change in Task Values.

PubMed

Matton, Nadine; Paubel, Pierre; Cegarra, Julien; Raufaste, Eric

2016-12-01

The objective was to characterize multitask resource reallocation strategies when managing subtasks with various assigned values. When solving a resource conflict in multitasking, Salvucci and Taatgen predict a globally rational strategy will be followed that favors the most urgent subtask and optimizes global performance. However, Katidioti and Taatgen identified a locally rational strategy that optimizes only a subcomponent of the whole task, leading to detrimental consequences on global performance. Moreover, the question remains open whether expertise would have an impact on the choice of the strategy. We adopted a multitask environment used for pilot selection with a change in emphasis on two out of four subtasks while all subtasks had to be maintained over a minimum performance. A laboratory eye-tracking study contrasted 20 recently selected pilot students considered as experienced with this task and 15 university students considered as novices. When two subtasks were emphasized, novices focused their resources particularly on one high-value subtask and failed to prevent both low-value subtasks falling below minimum performance. On the contrary, experienced people delayed the processing of one low-value subtask but managed to optimize global performance. In a multitasking environment where some subtasks are emphasized, novices follow a locally rational strategy whereas experienced participants follow a globally rational strategy. During complex training, trainees are only able to adjust their resource allocation strategy to subtask emphasis changes once they are familiar with the multitasking environment. © 2016, Human Factors and Ergonomics Society.

Low Female Literacy: Factors and Strategies

ERIC Educational Resources Information Center

Vasudeva Rao, B. S.; Gupta, P. Viswanadha

2006-01-01

Literacy is a process which dispels and promotes rational thinking and moulds human beings into becoming responsible citizens. The absence of literacy directly and indirectly retards the development of individuals, society, community and the country. For the success of any program, people should be motivated by providing necessary congenial…

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

PubMed Central

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

2016-01-01

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

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

PubMed Central

Corrigan, Patrick W.; Rüsch, Nicolas; Ben-Zeev, Dror; Sher, Tamara

2014-01-01

Purpose/Objective Many people with psychiatric disabilities do not benefit from evidence-based practices because they often do not seek out or fully adhere to them. One way psychologists have made sense of this rehabilitation and health decision process and subsequent behaviors (of which adherence might be viewed as one) is by proposing a “rational patient;” namely, that decisions are made deliberatively by weighing perceived costs and benefits of intervention options. Social psychological research, however, suggests limitations to a rational patient theory that impact models of health decision making. Design The research literature was reviewed for studies of rational patient models and alternative theories with empirical support. Special focus was on models specifically related to decisions about rehabilitation strategies for psychiatric disability. Results Notions of the rational patient evolved out of several psychological models including the health belief model, protection motivation theory, and theory of planned behavior. A variety of practice strategies evolved to promote rational decision making. However, research also suggests limitations to rational deliberations of health. (1) Rather than carefully and consciously considered, many health decisions are implicit, potentially occurring outside awareness. (2) Decisions are not always planful; often it is the immediate exigencies of a context rather than an earlier balance of costs and benefits that has the greatest effects. (3) Cool cognitions often do not dictate the process; emotional factors have an important role in health decisions. Each of these limitations suggests additional practice strategies that facilitate a person’s health decisions. Conclusions/Implications Old models of rational decision making need to be supplanted by multi-process models that explain supra-deliberative factors in health decisions and behaviors. PMID:24446671

The rational patient and beyond: implications for treatment adherence in people with psychiatric disabilities.

PubMed

Corrigan, Patrick W; Rüsch, Nicolas; Ben-Zeev, Dror; Sher, Tamara

2014-02-01

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. 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. 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. Old models of rational decision making need to be supplanted by multiprocess models that explain supradeliberative factors in health decisions and behaviors. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Affirmative action as organization development at the Johnson Space Center

NASA Technical Reports Server (NTRS)

Tryman, Mfanya Donald L.

1987-01-01

The role of affirmative actions is investigated as an interventionist Organization Development (OD) strategy for insuring equal opportunities at the NASA/Johnson Space Center. In doing so, an eclectic and holistic model is developed for the recruiting and hiring of minorities and females over the next five years. The strategy, approach, and assumptions for the model are quite different than those for JSC's five year plan. The study concludes that Organization development utilizing affirmative action is a valid means to bring about organizational change and renewal processes, and that an eclectic model of affirmative action is most suitable and rational in obtaining this end.

Predictive Game Theory

NASA Technical Reports Server (NTRS)

Wolpert, David H.

2005-01-01

Probability theory governs the outcome of a game; there is a distribution over mixed strat.'s, not a single "equilibrium". To predict a single mixed strategy must use our loss function (external to the game's players. Provides a quantification of any strategy's rationality. Prove rationality falls as cost of computation rises (for players who have not previously interacted). All extends to games with varying numbers of players.

Cooperation and stability through periodic impulses.

PubMed

Zhang, Bo-Yu; Cressman, Ross; Tao, Yi

2010-03-29

Basic games, where each individual chooses between two strategies, illustrate several issues that immediately emerge from the standard approach that applies strategic reasoning, based on rational decisions, to predict population behavior where no rationality is assumed. These include how mutual cooperation (which corresponds to the best outcome from the population perspective) can evolve when the only individually rational choice is to defect, illustrated by the Prisoner's Dilemma (PD) game, and how individuals can randomize between two strategies when neither is individually rational, illustrated by the Battle of the Sexes (BS) game that models male-female conflict over parental investment in offspring. We examine these questions from an evolutionary perspective where the evolutionary dynamics includes an impulsive effect that models sudden changes in collective population behavior. For the PD game, we show analytically that cooperation can either coexist with defection or completely take over the population, depending on the strength of the impulse. By extending these results for the PD game, we also show that males and females each evolve to a single strategy in the BS game when the impulsive effect is strong and that weak impulses stabilize the randomized strategies of this game.

American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Postoperative Gastrointestinal Dysfunction Within an Enhanced Recovery Pathway for Elective Colorectal Surgery.

PubMed

Hedrick, Traci L; McEvoy, Matthew D; Mythen, Michael Monty G; Bergamaschi, Roberto; Gupta, Ruchir; Holubar, Stefan D; Senagore, Anthony J; Gan, Tong Joo; Shaw, Andrew D; Thacker, Julie K M; Miller, Timothy E; Wischmeyer, Paul E; Carli, Franco; Evans, David C; Guilbert, Sarah; Kozar, Rosemary; Pryor, Aurora; Thiele, Robert H; Everett, Sotiria; Grocott, Mike; Abola, Ramon E; Bennett-Guerrero, Elliott; Kent, Michael L; Feldman, Liane S; Fiore, Julio F

2018-06-01

The primary driver of length of stay after bowel surgery, particularly colorectal surgery, is the time to return of gastrointestinal (GI) function. Traditionally, delayed GI recovery was thought to be a routine and unavoidable consequence of surgery, but this has been shown to be false in the modern era owing to the proliferation of enhanced recovery protocols. However, impaired GI function is still common after colorectal surgery, and the current literature is ambiguous with regard to the definition of postoperative GI dysfunction (POGD), or what is typically referred to as ileus. This persistent ambiguity has impeded the ability to ascertain the true incidence of the condition and study it properly within a research setting. Furthermore, a rational and standardized approach to prevention and treatment of POGD is needed. The second Perioperative Quality Initiative brought together a group of international experts to review the published literature and provide consensus recommendations on this important topic with the goal to (1) develop a rational definition for POGD that can serve as a framework for clinical and research efforts; (2) critically review the evidence behind current prevention strategies and provide consensus recommendations; and (3) develop rational treatment strategies that take into account the wide spectrum of impaired GI function in the postoperative period.

Agricultural Extension Services and the Issue of Equity in Agricultural Development.

ERIC Educational Resources Information Center

Monu, Erasmus D.

1981-01-01

Reviews experiments in Kenya and Nigeria attempting to modify the progressive-farmer strategy. Success requires that extension services recognize small farmers' ability to make their own rational decisions and involve farmers in planning and implementing extension programs. Available from: Rural Sociological Society, 325 Morgan Hall, University of…

Community Participation of the Elderly Chicano: A Model.

ERIC Educational Resources Information Center

Daley, John Michael; And Others

1989-01-01

Proposes strategies for development of participatory processes and systems that take into account reality of daily life in barrio for Chicano elderly. Recommends statistical data should be enriched by qualitative information for decision-making purposes: calm rationality of people discussing the problems of others should be balanced by fire of…

The Jomtien Plan of Action in the Sub-Saharan Context.

ERIC Educational Resources Information Center

Thiam, Iba Der

1990-01-01

Suggests that the means to eliminate illiteracy are available in Africa if nations devise and implement a strategy of action based on an effective political will and adopting a methodical, rational approach. Discusses the current situation, negative factors, repercussions on development, and future demands. Argues that promoting basic education…

Moral Reasoning in Genetics Education

ERIC Educational Resources Information Center

van der Zande, Paul; Brekelmans, Mieke; Vermunt, Jan D.; Waarlo, Arend Jan

2009-01-01

Recent neuropsychological research suggests that intuition and emotion play a role in our reasoning when we are confronted with moral dilemmas. Incorporating intuition and emotion into moral reflection is a rather new idea in the educational world, where rational reasoning is preferred. To develop a teaching and learning strategy to address this…

Pedagogical Strategies for Incorporating Behavioral Finance Concepts in Investment Courses

ERIC Educational Resources Information Center

Adams, Michael; Mullins, Terry; Thornton, Barry

2007-01-01

The traditional approach to teaching a course in investments is predicated upon the efficient market hypothesis, modern portfolio theory, and the assumption that decision-makers are rational, wealth optimizing entities. Recent developments in the arena of behavioral finance (BF) have raised questions about this approach. Although the idea of…

Rational approximations to rational models: alternative algorithms for category learning.

PubMed

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

2010-10-01

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 is thus explaining how optimal solutions can be approximated by psychological processes. We outline a general strategy for answering this question, namely to explore the psychological plausibility of approximation algorithms developed in computer science and statistics. In particular, we argue that Monte Carlo methods provide a source of rational process models that connect optimal solutions to psychological processes. We support this argument through a detailed example, applying this approach to Anderson's (1990, 1991) rational model of categorization (RMC), which involves a particularly challenging computational problem. Drawing on a connection between the RMC and ideas from nonparametric Bayesian statistics, we propose 2 alternative algorithms for approximate inference in this model. The algorithms we consider include Gibbs sampling, a procedure appropriate when all stimuli are presented simultaneously, and particle filters, which sequentially approximate the posterior distribution with a small number of samples that are updated as new data become available. Applying these algorithms to several existing datasets shows that a particle filter with a single particle provides a good description of human inferences.

Rational Improvement of Molar Absorptivity Guided by Oscillator Strength: A Case Study with Furoindolizine-Based Core Skeleton.

PubMed

Lee, Youngjun; Jo, Ala; Park, Seung Bum

2015-12-21

The rational improvement of photophysical properties can be highly valuable for the discovery of novel organic fluorophores. Using our new design strategy guided by the oscillator strength, we developed a series of full-color-tunable furoindolizine analogs with improved molar absorptivity through the fusion of a furan ring into the indolizine-based Seoul fluorophore. The excellent correlation between the computable values (oscillator strength and theoretical S0 -S1 energy gap) and photophysical properties (molar absorptivity and emission wavelength) confirmed the effectualness of our design strategy. © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

What Information Theory Says about Bounded Rational Best Response

NASA Technical Reports Server (NTRS)

Wolpert, David H.

2005-01-01

Probability Collectives (PC) provides the information-theoretic extension of conventional full-rationality game theory to bounded rational games. Here an explicit solution to the equations giving the bounded rationality equilibrium of a game is presented. Then PC is used to investigate games in which the players use bounded rational best-response strategies. Next it is shown that in the continuum-time limit, bounded rational best response games result in a variant of the replicator dynamics of evolutionary game theory. It is then shown that for team (shared-payoff) games, this variant of replicator dynamics is identical to Newton-Raphson iterative optimization of the shared utility function.

Occupational musculoskeletal and mental health: Significance of rationalization and opportunities to create sustainable production systems - A systematic review.

PubMed

Westgaard, R H; Winkel, J

2011-01-01

This literature review aims to identify occupational musculoskeletal and mental health effects of production system rationalization as well as organizational-level measures that may improve health outcome ("modifiers" in this review). A short review of the effect of ergonomic interventions is included as background and rationalization is discussed as a theoretical concept. Indicator variables for occupational musculoskeletal and mental health and related risk factors are presented. Variables with a generalized format were allowed in the literature searches (e.g., job satisfaction and absenteeism were accepted as risk factor and health indicator, respectively), suitable for the research fields of work sociology, organization science, human resource management (HRM) and economics research. One hundred and sixty-two studies of rationalization effects on health and risk factors and 72 organization-level modifier results were accepted into the final database. Entries were sorted by rationalization strategy and work life sector, and trends in outcome (positive, mixed, no effect, or negative effect on health and risk factors) were determined. Rationalizations have a dominant negative effect on health and risk factors (57% negative, 19% positive); the most negative effects were found for downsizing and restructuring rationalizations in general (71 studies negative, 13 positive) and for the health care sector in particular (36 studies negative, 2 positive). The rationalization strategy High Performance Work System (HPWS) was associated with the highest fraction positive outcome studies (6 of 10 studies). Other rationalization strategies (lean practices, parallel vs. serial production and mechanization level) reported intermediate results, in part dependent on work life sector, but also on the year when studies were carried out. Worker participation, resonant management style, information, support, group autonomy and procedural justice were modifiers with favourable influence on outcome. It is concluded that production system rationalization represents a pervasive work life intervention without a primary occupational health focus. It has considerable and mostly negative influence on worker health, but this can be reduced by attention to modifiers. The results create a basis for new priorities in ergonomic intervention research. Copyright © 2010 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Neurocognitive inefficacy of the strategy process.

PubMed

Klein, Harold E; D'Esposito, Mark

2007-11-01

The most widely used (and taught) protocols for strategic analysis-Strengths, Weaknesses, Opportunities, and Threats (SWOT) and Porter's (1980) Five Force Framework for industry analysis-have been found to be insufficient as stimuli for strategy creation or even as a basis for further strategy development. We approach this problem from a neurocognitive perspective. We see profound incompatibilities between the cognitive process-deductive reasoning-channeled into the collective mind of strategists within the formal planning process through its tools of strategic analysis (i.e., rational technologies) and the essentially inductive reasoning process actually needed to address ill-defined, complex strategic situations. Thus, strategic analysis protocols that may appear to be and, indeed, are entirely rational and logical are not interpretable as such at the neuronal substrate level where thinking takes place. The analytical structure (or propositional representation) of these tools results in a mental dead end, the phenomenon known in cognitive psychology as functional fixedness. The difficulty lies with the inability of the brain to make out meaningful (i.e., strategy-provoking) stimuli from the mental images (or depictive representations) generated by strategic analysis tools. We propose decreasing dependence on these tools and conducting further research employing brain imaging technology to explore complex data handling protocols with richer mental representation and greater potential for strategy creation.

[Immunotherapy: a therapeutic revolution against prostate cancer?].

PubMed

Pracht, Marc; Herrera, Fernanda; Tawadros, Thomas; Berthold, Dominik

2013-05-22

The interaction between the immune system and cancer was an area of research interest for several decades. The recent U.S. Food and Drug Administration approval of sipuleucel-T and ipilimumab stimulated broader interest in manipulating immunity to fight cancer. In the context of prostate cancer, the immunotherapy strategies under development are therapeutic vaccination strategies, such as sipuleucel-T and PROSTVAC-VF, or immune checkpoint blockade of CTLA-4. Improved understanding of the immune responses generated by the development of predictive biomarkers for patient selection will guide rational combinations of these treatments and provide new treatment options in prostate cancer.

Melioration as rational choice: sequential decision making in uncertain environments.

PubMed

Sims, Chris R; Neth, Hansjörg; Jacobs, Robert A; Gray, Wayne D

2013-01-01

Melioration-defined as choosing a lesser, local gain over a greater longer term gain-is a behavioral tendency that people and pigeons share. As such, the empirical occurrence of meliorating behavior has frequently been interpreted as evidence that the mechanisms of human choice violate the norms of economic rationality. In some environments, the relationship between actions and outcomes is known. In this case, the rationality of choice behavior can be evaluated in terms of how successfully it maximizes utility given knowledge of the environmental contingencies. In most complex environments, however, the relationship between actions and future outcomes is uncertain and must be learned from experience. When the difficulty of this learning challenge is taken into account, it is not evident that melioration represents suboptimal choice behavior. In the present article, we examine human performance in a sequential decision-making experiment that is known to induce meliorating behavior. In keeping with previous results using this paradigm, we find that the majority of participants in the experiment fail to adopt the optimal decision strategy and instead demonstrate a significant bias toward melioration. To explore the origins of this behavior, we develop a rational analysis (Anderson, 1990) of the learning problem facing individuals in uncertain decision environments. Our analysis demonstrates that an unbiased learner would adopt melioration as the optimal response strategy for maximizing long-term gain. We suggest that many documented cases of melioration can be reinterpreted not as irrational choice but rather as globally optimal choice under uncertainty.

Habermas, Lifeworld and Rationality: Towards a Comprehensive Model of Lifelong Learning

ERIC Educational Resources Information Center

Regmi, Kapil Dev

2017-01-01

Major supranational organisations such as the Organisation for Economic Cooperation and Development, the European Union, and the World Bank have used lifelong learning as a strategy to boost economic competitiveness both at individual and national levels. In the literature related to lifelong learning this is characterised as the economistic model…

Taming the Beast: Choice & Control in the Electronic Jungle.

ERIC Educational Resources Information Center

Ohler, Jason

This book discusses and develops similar strategies for a variety of new media, primarily focusing on those that are emerging by way of the Internet. It also evaluates whether these new technologies are helpful in satisfying user need. Chapter One explores the tension created by an emotional versus rational relationship with technology. It…

Toward the Development of a Theory of Bereavement Guilt: Sources of Guilt in Bereaved Parents.

ERIC Educational Resources Information Center

Miles, Margaret Shandor; Demi, Alice Sterner

1984-01-01

Identifies five sources of guilt in bereaved parents: cultural role, death causation, moral, survivor, and recovery guilt. A pilot study of 28 bereaved parents provided partial support for the model and suggested an additional category: grief guilt. Rationalizing and sharing were the most common guilt-ameliorating strategies. (JAC)

Improving fermented quality of cider vinegar via rational nutrient feeding strategy.

PubMed

Qi, Zhengliang; Dong, Die; Yang, Hailin; Xia, Xiaole

2017-06-01

This work aimed to find a rational nutrient feeding strategy for cider vinegar fermentation based on adequate information on the nutritional requirement of acetic acid bacteria. Through single nutrient lack experiment assay, necessary nutrient recipe for Acetobacter pasteurianus CICIM B7003 in acetous fermentation was confirmed. Compounds from the essential nutrient recipe were tested further to find out the key substrates significantly influencing cider vinegar fermentation. The findings showed that aspartate, glutamate, proline and tryptophan should be considered in detail for optimizing nutritional composition of cider. Finally, a nutrient feeding strategy that simultaneously adds proline, glutamate, aspartate and tryptophan to form final concentrations of 0.02g/L, 0.03g/L, 0.01g/L and 0.005g/L in cider was achieved by orthogonal experiment design. Comparing to the original fermentation, the yield of acetic acid from alcohol reached 93.3% and the concentration of most volatile flavor compounds increased with the rational nutrient feeding strategy. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Psychotropic drugs in the Family Health Strategy: profile of use, access and strategies to promote rational use].

PubMed

da Rocha, Bruno Simas; Werlang, Maria Cristina

2013-11-01

The use of psychotropic drugs is on the increase, and there are few studies in Brazil investigating their use in the population and in Primary Health Care (PHC). This study aimed to determine the prevalence and patterns of psychotropic drug use by patients of a Family Health Unit in Porto Alegre, through an observational, descriptive, retrospective and cross-sectional study. The sample consisted of patients who received prescriptions for controlled psychotropic drugs and the data collected from medical records. The study included 329 patients, with prevalence of the use of psychotropic drugs of 7.30%, mean age of 53.14 (SD = 18.58) years and 72% female. The average number of prescribed drugs and psychotropic drugs per user was 3.56 (SD = 2.36) and 1.66 (SD = 0.90), respectively. The most widely used class was antidepressants, followed by antiepileptics, anxiolytics and antipsychotics. It is necessary to develop strategies to improve access, treatment of patients and rational use of psychotropic drugs, including the revision of lists of essential drugs and training of professionals in PHC.

A Thoroughly Validated Virtual Screening Strategy for Discovery of Novel HDAC3 Inhibitors.

PubMed

Hu, Huabin; Xia, Jie; Wang, Dongmei; Wang, Xiang Simon; Wu, Song

2017-01-18

Histone deacetylase 3 (HDAC3) has been recently identified as a potential target for the treatment of cancer and other diseases, such as chronic inflammation, neurodegenerative diseases, and diabetes. Virtual screening (VS) is currently a routine technique for hit identification, but its success depends on rational development of VS strategies. To facilitate this process, we applied our previously released benchmarking dataset, i.e., MUBD-HDAC3 to the evaluation of structure-based VS (SBVS) and ligand-based VS (LBVS) combinatorial approaches. We have identified FRED (Chemgauss4) docking against a structural model of HDAC3, i.e., SAHA-3 generated by a computationally inexpensive "flexible docking", as the best SBVS approach and a common feature pharmacophore model, i.e., Hypo1 generated by Catalyst/HipHop as the optimal model for LBVS. We then developed a pipeline that was composed of Hypo1, FRED (Chemgauss4), and SAHA-3 sequentially, and demonstrated that it was superior to other combinations in terms of ligand enrichment. In summary, we present the first highly-validated, rationally-designed VS strategy specific to HDAC3 inhibitor discovery. The constructed pipeline is publicly accessible for the scientific community to identify novel HDAC3 inhibitors in a time-efficient and cost-effective way.

A Thoroughly Validated Virtual Screening Strategy for Discovery of Novel HDAC3 Inhibitors

PubMed Central

Hu, Huabin; Xia, Jie; Wang, Dongmei; Wang, Xiang Simon; Wu, Song

2017-01-01

Histone deacetylase 3 (HDAC3) has been recently identified as a potential target for the treatment of cancer and other diseases, such as chronic inflammation, neurodegenerative diseases, and diabetes. Virtual screening (VS) is currently a routine technique for hit identification, but its success depends on rational development of VS strategies. To facilitate this process, we applied our previously released benchmarking dataset, i.e., MUBD-HDAC3 to the evaluation of structure-based VS (SBVS) and ligand-based VS (LBVS) combinatorial approaches. We have identified FRED (Chemgauss4) docking against a structural model of HDAC3, i.e., SAHA-3 generated by a computationally inexpensive “flexible docking”, as the best SBVS approach and a common feature pharmacophore model, i.e., Hypo1 generated by Catalyst/HipHop as the optimal model for LBVS. We then developed a pipeline that was composed of Hypo1, FRED (Chemgauss4), and SAHA-3 sequentially, and demonstrated that it was superior to other combinations in terms of ligand enrichment. In summary, we present the first highly-validated, rationally-designed VS strategy specific to HDAC3 inhibitor discovery. The constructed pipeline is publicly accessible for the scientific community to identify novel HDAC3 inhibitors in a time-efficient and cost-effective way. PMID:28106794

[Strategies to prevent bacteriophage infection in industrial fermentation].

PubMed

Shen, Juntao; Xiu, Zhilong

2017-12-25

During the development of bacteria-based biotechnology, bacteriophage infection is one of the constant threats and troublesome problems in industrial fermentation. The core of puzzled bacteriophage infection is a complex arm race of coevolution between bacteriophages and their hosts where bacteriophage has evolved lots of escaped ways against bacterial resistance mechanisms. The strategies of rationally designing factories and rotation of starter strains could reduce the risk of bacteriophage infection, but often fail to avoid. Genetic engineering to increase bacterial resistance is one of the strategies to prevent bacteriophage infection and more knowledge about bacteriophage and its host is needed. Recently, there are some new findings on bacterial resistance mechanisms which provide new solutions for bacteriophage infection. For example, it is possible for a rational design of resistant strains to use CRISPR-Cas based technologies just based on the sequences of bacteriophages. Moreover, it is also possible to avoid the escape of bacteriophage by iteratively building up resistance levels to generate robust industrial starter cultures. Quorum-sensing signal molecules have recently been proved to be involved in the interactions between bacteria and bacteriophages, which provides a possible way to solve bacteriophage infection from a population level. Finally, the rapid development of bacteriophage genome editing and synthetic biology will bring some new cues for preventing bacteriophage infection in industrial fermentation.

Symmetry warrants rational cooperation by co-action in Social Dilemmas.

PubMed

Sasidevan, V; Sinha, Sitabhra

2015-08-12

Is it rational for selfish individuals to cooperate? The conventional answer based on analysis of games such as the Prisoners Dilemma (PD) is that it is not, even though mutual cooperation results in a better outcome for all. This incompatibility between individual rationality and collective benefit lies at the heart of questions about the evolution of cooperation, as illustrated by PD and similar games. Here, we argue that this apparent incompatibility is due to an inconsistency in the standard Nash framework for analyzing non-cooperative games and propose a new paradigm, that of the co-action equilibrium. As in the Nash solution, agents know that others are just as rational as them and taking this into account lead them to realize that others will independently adopt the same strategy, in contrast to the idea of unilateral deviation central to Nash equilibrium thinking. Co-action equilibrium results in better collective outcomes for games representing social dilemmas, with relatively "nicer" strategies being chosen by rational selfish individuals. In particular, the dilemma of PD gets resolved within this framework, suggesting that cooperation can evolve in nature as the rational outcome even for selfish agents, without having to take recourse to additional mechanisms for promoting it.

Rational design and evolutional fine tuning of Saccharomyces cerevisiae for biomass breakdown.

PubMed

Hasunuma, Tomohisa; Ishii, Jun; Kondo, Akihiko

2015-12-01

Conferring biomass hydrolysis activity on yeast through genetic engineering has paved the way for the development of groundbreaking processes for producing liquid fuels and commodity chemicals from lignocellulosic biomass. However, the overproduction and misfolding of heterologous and endogenous proteins can trigger cellular stress, increasing the metabolic burden and retarding growth. Improving the efficiency of lignocellulosic breakdown requires engineering of yeast secretory pathway based on system-wide metabolic analysis as well as DNA constructs for enhanced cellulase gene expression with advanced molecular biology tools. Also, yeast is subjected to severe stress due to toxic compounds generated during lignocellulose pretreatment in consolidated saccharification and fermentation processes. The prospect for development of robust yeast strains makes combining evolutionary and rational engineering strategies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Rationality Validation of a Layered Decision Model for Network Defense

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

Wei, Huaqiang; Alves-Foss, James; Zhang, Du

2007-08-31

We propose a cost-effective network defense strategy built on three key: three decision layers: security policies, defense strategies, and real-time defense tactics for countering immediate threats. A layered decision model (LDM) can be used to capture this decision process. The LDM helps decision-makers gain insight into the hierarchical relationships among inter-connected entities and decision types, and supports the selection of cost-effective defense mechanisms to safeguard computer networks. To be effective as a business tool, it is first necessary to validate the rationality of model before applying it to real-world business cases. This paper describes our efforts in validating the LDMmore » rationality through simulation.« less

Estimation of the relationship between growth, consumption, and energy allocation in juvenile pacific cod (Gadus macrocephalus) as a function of temperature and ration

NASA Astrophysics Data System (ADS)

Sreenivasan, Ashwin; Heintz, Ron

2016-10-01

Pacific cod (Gadus macrocephalus) are generalist predators in the Gulf of Alaska (GOA), and are an important predator on other commercially important species. Efficient management of this species can benefit by knowing how these fish adapt to changing environmental conditions, with a focus on how growth and condition are affected by changes in temperature and diet. We conducted a feeding study to understand the relationship between growth, ration, and temperature, and how these factors interact to affect energy allocation strategies. Since growth and condition of juveniles can determine recruitment into the population, this study focused on growth and consumption of age 1+Pacific cod held over 4 temperature treatments (4 °C, 8 °C, 12 °C, and 16 °C) and 3 ration levels (unlimited ration, medium ration, and low ration). We also compared cellular nucleic acid (RNA/DNA) ratios, an instantaneous growth index, total-body lipid, and proximate composition between fish. At 4 °C, 8 °C, and 12 °C, fish at medium and low rations had higher growth rates relative to fish at high rations. Higher food consumption appears to negatively affect digestive ability, assimilation efficiency, and nutrient utilization. RNA/DNA was clearly correlated with growth rates at 4 °C and 8 °C, but this relationship did not hold at higher temperatures. A secondary growth study was conducted to test the reliability of the growth/consumption models derived from the main growth study. Temperature influenced energy reserves (lipid) while tissue growth (protein) was influenced by ration level. Average lipid values were higher at 4 °C than at 8 °C or 12 °C, suggesting a predisposition to heightened lipid synthesis at colder temperatures. Longer durations of warmer water temperature in the GOA could consequently affect energy allocation strategies, with dietary changes in the field potentially amplifying this effect in cold and warm years. This energy allocation strategy could be detrimental with warmer temperatures predicted in the GOA.

The Research on Integrated Strategy of Supply Chain Information Systems in the Automobile Industry Based on Order-To-Delivery Mode

NASA Astrophysics Data System (ADS)

Li, Ming; Gan, Lianzhen; He, Xuefeng

The automotive industry there are different degrees of impairment of many companies supply chain IT strategy. In this paper, in which the automotive industry supply chain management business cooperation between enterprises loose, poor exchange of information leading to the presence or delays in product customization, supply of raw materials, material control, production planning and control, sales and service and a fast response propose a series of typical problems of scientific and rational supply chain information integration strategy. The strategy through the development system integration platform, improve internal ERP system, implementation of supply chain management and other methods. Put some protection principles in the information process, to ensure the correct implementation of supply chain IT strategy, and ultimately achieve collaborative business development concept and enhance the automotive industry as a whole level of information.

Quantitative analysis to guide orphan drug development.

PubMed

Lesko, L J

2012-08-01

The development of orphan drugs for rare diseases has made impressive strides in the past 10 years. There has been a surge in orphan drug designations, but new drug approvals have not kept up. This article presents a three-pronged hierarchical strategy for quantitative analysis of data at the descriptive, mechanistic, and systems levels of the biological system that could represent a standardized and rational approach to orphan drug development. Examples are provided to illustrate the concept.

ARO-YIP (Materials By Design): Organic Photovoltaic Multiferroics

DTIC Science & Technology

Materials-by- design and self-assembly principles are applied to organic functional materials to control their morphology, interface, and crystalline...multifunctional properties, such as dielectric, magnetic, optoelectronic, and magnetoelectric coupling behaviors. The control of organic crystallization and...electronics. In this project, we aim at utilizing the material design and assembly strategies to rationally develop organic multiferroic-photovoltaics

Are Middle School Mathematics Teachers Able to Solve Word Problems without Using Variable?

ERIC Educational Resources Information Center

Gökkurt Özdemir, Burçin; Erdem, Emrullah; Örnek, Tugba; Soylu, Yasin

2018-01-01

Many people consider problem solving as a complex process in which variables such as "x," "y" are used. Problems may not be solved by only using "variable." Problem solving can be rationalized and made easier using practical strategies. When especially the development of children at younger ages is considered, it is…

Pruritus: Management Algorithms and Experimental Therapies

PubMed Central

Steinhoff, Martin; Cevikbas, Ferda; Ikoma, Akihiko; Berger, Timothy G.

2013-01-01

Pruritus (itch) is a major symptom in many dermatologic as well as systemic diseases and has a dramatic impact on the quality of life in these patients. The symptom of itch has to be treated on the basis of its pathophysiology and its underlying disease. In daily practice, a “quick” diagnosis of the underlying disease is often difficult, although a rapid relief of the itch is desired. We often treat patients on the basis of the symptomatology. A rational therapeutic ladder for a symptomatic therapy is useful until the final diagnosis has been confirmed. There are probably many subtypes of pruritus, just as there are many diseases that cause itch. The pathophysiology in many subtypes of pruritus is still poorly understood, hindering a rapid and targeted treatment strategy. An extensive diagnostic workup is often required to determine the final cause(s) of the itch. Thus, in daily life, physicians often start with a more or less rational therapeutic strategy to combat the debilitating itch. We present possible therapeutic ladders that form the basis for effective therapeutic itch strategies in various diseases. On the basis of our current knowledge about the different pathophysiologies of itch, on clinical trials or case reports, and our own clinical experience, we aim to present therapeutic ladders for the rapid as well as long-term management of itch. Finally, we summarize current exciting developments of experimental strategies in itch research and in clinical development for itch therapy. PMID:21767775

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

ERIC Educational Resources Information Center

Bernard, Michael E.

1990-01-01

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

Novel technologies provide more engineering strategies for amino acid-producing microorganisms.

PubMed

Gu, Pengfei; Su, Tianyuan; Qi, Qingsheng

2016-03-01

Traditionally, amino acid-producing strains were obtained by random mutagenesis and subsequent selection. With the development of genetic and metabolic engineering techniques, various microorganisms with high amino acid production yields are now constructed by rational design of targeted biosynthetic pathways. Recently, novel technologies derived from systems and synthetic biology have emerged and open a new promising avenue towards the engineering of amino acid production microorganisms. In this review, these approaches, including rational engineering of rate-limiting enzymes, real-time sensing of end-products, pathway optimization on the chromosome, transcription factor-mediated strain improvement, and metabolic modeling and flux analysis, were summarized with regard to their application in microbial amino acid production.

The use of content analysis in the assessment of medical controversies.

PubMed

de Villiers, F P

1991-12-01

Medicine is fraught with controversies, and several strategies have been developed in order to reach rational conclusions. Examples are using more subjects or an improved research design, developing consensus statements or using meta-analysis. An additional strategy is described in this paper. The language content of scientific papers is examined to establish whether the authors use factual (informational) language or emotional appeals (directive language) to convince the reader. This type of content analysis is then applied to a sample controversy. The paper shows that directive language content analysis can be applied effectively to scientific publications to clarify the basis of and reasoning behind some controversies.

[Strategy programming for acupuncture development along One-Belt-One-Road countries].

PubMed

Yang, Yuyang; Shen, Zhixiang; Wu, Zhongchao; Luo, Lu; Liu, Jingyuan; Liu, Baoyan

2017-04-12

Acupuncture has been applied in 183 countries and regions and gradually become a name card as TCM spreads across the world. The international influence of which plays a significant role in enhancing TCM development. The laws and regulations of TCM acupuncture along One-Belt-One-Road countries were compared and analyzed in this article. With comprehensive research and analysis, the international development strategy of acupuncture was rationally proposed. Combined with the historical background of China's national initiative One-Belt-One-Road, the acupuncture was taken as a breakthrough to lead the global spreading of TCM culture and Chinese herbs, so as to enhance China's soft strength, which could further create a fine cultural environment for the economic prosperity of One-Belt-One-Road countries. In addition, the strategy selection for China regarding TCM acupuncture development along One-Belt-One-Road countries was proposed, and the suggestive solution and implementation strategy for the essential missions and significant issues were provided.

Therapists' causal attributions of clients' problems and selection of intervention strategies.

PubMed

Royce, W S; Muehlke, C V

1991-04-01

Therapists' choices of intervention strategies are influenced by many factors, including judgments about the bases of clients' problems. To assess the relationships between such causal attributions and the selection of intervention strategies, 196 counselors, psychologists, and social workers responded to the written transcript of a client's interview by answering two questionnaires, a 1982 scale (Causal Dimension Scale by Russell) which measured causal attribution of the client's problem, and another which measured preference for emotional, rational, and active intervention strategies in dealing with the client, based on the 1979 E-R-A taxonomy of Frey and Raming. A significant relationship was found between the two sets of variables, with internal attributions linked to rational intervention strategies and stable attributions linked to active strategies. The results support Halleck's 1978 hypothesis that theories of psychotherapy tie interventions to etiological considerations.

Rationality, irrationality and escalating behavior in lowest unique bid auctions.

PubMed

Radicchi, Filippo; Baronchelli, Andrea; Amaral, Luís A N

2012-01-01

Information technology has revolutionized the traditional structure of markets. The removal of geographical and time constraints has fostered the growth of online auction markets, which now include millions of economic agents worldwide and annual transaction volumes in the billions of dollars. Here, we analyze bid histories of a little studied type of online auctions--lowest unique bid auctions. Similarly to what has been reported for foraging animals searching for scarce food, we find that agents adopt Lévy flight search strategies in their exploration of "bid space". The Lévy regime, which is characterized by a power-law decaying probability distribution of step lengths, holds over nearly three orders of magnitude. We develop a quantitative model for lowest unique bid online auctions that reveals that agents use nearly optimal bidding strategies. However, agents participating in these auctions do not optimize their financial gain. Indeed, as long as there are many auction participants, a rational profit optimizing agent would choose not to participate in these auction markets.

Rationality, Irrationality and Escalating Behavior in Lowest Unique Bid Auctions

PubMed Central

Radicchi, Filippo; Baronchelli, Andrea; Amaral, Luís A. N.

2012-01-01

Information technology has revolutionized the traditional structure of markets. The removal of geographical and time constraints has fostered the growth of online auction markets, which now include millions of economic agents worldwide and annual transaction volumes in the billions of dollars. Here, we analyze bid histories of a little studied type of online auctions – lowest unique bid auctions. Similarly to what has been reported for foraging animals searching for scarce food, we find that agents adopt Lévy flight search strategies in their exploration of “bid space”. The Lévy regime, which is characterized by a power-law decaying probability distribution of step lengths, holds over nearly three orders of magnitude. We develop a quantitative model for lowest unique bid online auctions that reveals that agents use nearly optimal bidding strategies. However, agents participating in these auctions do not optimize their financial gain. Indeed, as long as there are many auction participants, a rational profit optimizing agent would choose not to participate in these auction markets. PMID:22279553

Cluster-mediated assembly enables step-growth copolymerization from binary nanoparticle mixtures with rationally designed architectures† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c8sc00220g

PubMed Central

Zhang, Xianfeng; Lv, Longfei; Wu, Guanhong; Yang, Dong

2018-01-01

Directed co-assembly of binary nanoparticles (NPs) into one-dimensional copolymer-like chains is fascinating but challenging in the realm of material science. While many strategies have been developed to induce the polymerization of NPs, it remains a grand challenge to produce colloidal copolymers with widely tailored compositions and precisely controlled architectures. Herein we report a robust colloidal polymerization strategy, which enables the growth of sophisticated NP chains with elaborately designed structures. By quantifying NP assembly statistics and kinetics, we establish that the linear assembly of colloidal NPs, with the assistance of PbSO4 clusters, follows a step-growth polymerization mechanism, and on the basis of this, we design and fabricate NP chains structurally analogous to random, block, and alternating copolymers, respectively. Our studies offer mechanistic insights into cluster-mediated colloidal polymerization, paving the way toward the rational synthesis of colloidal copolymers with quantitatively predicted architectures and functionalities. PMID:29862003

A Model for Teaching Rational Behavior Skills to Emotionally Disturbed Youth in a Public School Setting.

ERIC Educational Resources Information Center

Patton, Patricia L.

1985-01-01

Describes a model used to teach rational behavior skills to 34 emotionally disturbed adolescents. Discusses teaching, training, and counseling strategies. The group demonstrated significant positive changes in learning and personality variables, but not behavior. (JAC)

Toward metabolic engineering in the context of system biology and synthetic biology: advances and prospects.

PubMed

Liu, Yanfeng; Shin, Hyun-dong; Li, Jianghua; Liu, Long

2015-02-01

Metabolic engineering facilitates the rational development of recombinant bacterial strains for metabolite overproduction. Building on enormous advances in system biology and synthetic biology, novel strategies have been established for multivariate optimization of metabolic networks in ensemble, spatial, and dynamic manners such as modular pathway engineering, compartmentalization metabolic engineering, and metabolic engineering guided by genome-scale metabolic models, in vitro reconstitution, and systems and synthetic biology. Herein, we summarize recent advances in novel metabolic engineering strategies. Combined with advancing kinetic models and synthetic biology tools, more efficient new strategies for improving cellular properties can be established and applied for industrially important biochemical production.

The rationing agenda in the NHS. Rationing Agenda Group.

PubMed Central

New, B.

1996-01-01

The Rationing Agenda Group has been founded to deepen the British debate on rationing health care. It believes that rationing in health care is inevitable and that the public must be involved in the debate about issues relating to rationing. The group comprises people from all parts of health care, none of whom represent either their group or their institutions. RAG has begun by producing this document, which attempts to set an agenda of all the issues that need to be considered when debating the rationing of health care. We hope for responses to the document. The next stage will be to incorporate the responses into the agenda. Then RAG will divide the agenda into manageable chunks and commission expert, detailed commentaries. From this material a final paper will be published and used to prompt public debate. This stage should be reached early in 1997. While these papers are being prepared RAG is developing ways to involve the public in the debate and evaluate the whole process. We present as neutrally as possible all the issues related to rationing and priority setting in the NHS. We focus on the NHS for two reasons. Firstly, for those of us resident in the United Kingdom the NHS is the health care system with which we are most familiar and most concerned. Secondly, focusing on one system alone allows more coherent analysis than would be possible if issues in other systems were included as well. Our concern is with the delivery of health care, not its finance, though we discuss the possible effects of changing the financing system of the NHS. Finally, though our position is neutral, we hold two substantive views--namely, that rationing is unavoidable and that there should be more explicit debate about the principles and issues concerned. We consider the issues under four headings: preliminaries, ethics, democracy, and empirical questions. Preliminaries deal with the semantics of rationing, whether rationing is necessary, and with the range of services to which rationing relates. Under ethics and democracy are the substantive issues of principle and theory. The final section deals with empirical questions and those relating to the practicality of various strategies. PMID:8664673

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

NASA Astrophysics Data System (ADS)

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

2013-04-01

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

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

PubMed

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

2013-04-01

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

It's in the Milk: Feeding the Microbiome to Promote Infant Growth.

PubMed

Bashiardes, Stavros; Thaiss, Christoph A; Elinav, Eran

2016-03-08

Malnutrition is a global health burden affecting the development of millions of children worldwide, but the effects of current treatment strategies are modest. Charbonneau et al. (2016) identify sialylated oligosaccharides in breast milk as microbiota-dependent growth-promoting metabolites, paving the way for a new rational treatment of severe infant stunting. Copyright © 2016 Elsevier Inc. All rights reserved.

Using Paper Folding, Fraction Walls, and Number Lines to Develop Understanding of Fractions for Students from Years 5-8

ERIC Educational Resources Information Center

Pearn, Catherine Ann

2007-01-01

Several researchers have noted how children's whole number schemes can interfere with their efforts to learn fractions. An Australian study found that children who were successful with the solution of rational number tasks exhibited greater whole number knowledge and more flexible solution strategies. Behr and Post (1988) indicated that children…

Rational models as theories - not standards - of behavior.

PubMed

McKenzie, Craig R.M.

2003-09-01

When people's behavior in laboratory tasks systematically deviates from a rational model, the implication is that real-world performance could be improved by changing the behavior. However, recent studies suggest that behavioral violations of rational models are at least sometimes the result of strategies that are well adapted to the real world (and not necessarily to the laboratory task). Thus, even if one accepts that certain behavior in the laboratory is irrational, compelling evidence that real-world behavior ought to change accordingly is often lacking. It is suggested here that rational models be seen as theories, and not standards, of behavior.

Rationality and self-interest as economic-exchange strategy in borderline personality disorder: Game theory, social preferences, and interpersonal behavior.

PubMed

Jeung, Haang; Schwieren, Christiane; Herpertz, Sabine C

2016-12-01

Borderline Personality Disorder (BPD) is characterized by severe and persistent impairments in interpersonal functioning. Given the complexity of social interactions, studying the interactive behavior of BPD patients is challenging. One way to implement both tight experimental control and realistic, externally valid settings is to use game-theoretical experiments. This review discusses findings from economic exchange studies in BPD against the background of game-theoretical literature. BPD patients do not seem to derive utility from mutual cooperation with others and appear not to "forgive" a partner's unfairness. By pursuing a strategy of negative reciprocity, BPD patients seem to act mostly "rationally" and in their own self-interest. Their "grim trigger strategy" resembles the theoretical ideal of the rational and self-interested agent homo economicus. Finally, we summarize how research findings from economics and clinical psychiatry may be mutually enriching and propose new research ideas in this fascinating field. Copyright © 2016 Elsevier Ltd. All rights reserved.

Adding a Systemic Touch to Rational-Emotive Therapy for Families.

ERIC Educational Resources Information Center

Russell, Todd T.; Morrill, Correen M.

1989-01-01

Proposes a theoretical and practical hybrid model for family counseling based on integrating the rational-emotive and family systems approach. Notes that these combined approaches offer the counselor a systematic theoretical structure for conceptualizing family dysfunction, from which additional strategies for changing inappropriate belief systems…

Rational choice and the political bases of changing Israeli counterinsurgency strategy.

PubMed

Brym, Robert J; Andersen, Robert

2011-09-01

Israeli counterinsurgency doctrine holds that the persistent use of credible threat and disproportionate military force results in repeated victories that eventually teach the enemy the futility of aggression. The doctrine thus endorses classical rational choice theory's claim that narrow cost-benefit calculations shape fixed action rationales. This paper assesses whether Israel's strategic practice reflects its counterinsurgency doctrine by exploring the historical record and the association between Israeli and Palestinian deaths due to low-intensity warfare. In contrast to the expectations of classical rational choice theory, the evidence suggests that institutional, cultural and historical forces routinely override simple cost-benefit calculations. Changing domestic and international circumstances periodically cause revisions in counterinsurgency strategy. Credible threat and disproportionate military force lack the predicted long-term effect. © London School of Economics and Political Science 2011.

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

PubMed

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.

Engineering of carboligase activity reaction in Candida glabrata for acetoin production.

PubMed

Li, Shubo; Xu, Nan; Liu, Liming; Chen, Jian

2014-03-01

Utilization of Candida glabrata overproducing pyruvate is a promising strategy for high-level acetoin production. Based on the known regulatory and metabolic information, acetaldehyde and thiamine were fed to identify the key nodes of carboligase activity reaction (CAR) pathway and provide a direction for engineering C. glabrata. Accordingly, alcohol dehydrogenase, acetaldehyde dehydrogenase, pyruvate decarboxylase, and butanediol dehydrogenase were selected to be manipulated for strengthening the CAR pathway. Following the rational metabolic engineering, the engineered strain exhibited increased acetoin biosynthesis (2.24 g/L). In addition, through in silico simulation and redox balance analysis, NADH was identified as the key factor restricting higher acetoin production. Correspondingly, after introduction of NADH oxidase, the final acetoin production was further increased to 7.33 g/L. By combining the rational metabolic engineering and cofactor engineering, the acetoin-producing C. glabrata was improved stepwise, opening a novel pathway for rational development of microorganisms for bioproduction. Copyright © 2013. Published by Elsevier Inc.

Renewing functionalized graphene as electrodes for high-performance supercapacitors.

PubMed

Fang, Yan; Luo, Bin; Jia, Yuying; Li, Xianglong; Wang, Bin; Song, Qi; Kang, Feiyu; Zhi, Linjie

2012-12-11

An acid-assisted ultrarapid thermal strategy is developed for constructing specifically functionalized graphene. The electrochemical performance of functionalized graphene can be boosted via elaborate coupling between the pseudocapacitance and the electronic double layer capacitance through rationally tailoring the structure of graphene sheets. This presents an opportunity for developing further high-performance graphene-based electrodes to bridge the performance gap between traditional capacitors and batteries. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Food distribution as a guarantee for nutrition and health: China's experience.

PubMed

Wang, V L

1976-01-01

In China, agriculture, health, education, and welfare are intricately woven as part of the development and its relationship to health programs, the strategy of food rationing and the "private plot" to improve nutrition and health, and the balance of food and population in the Chinese society. China's nutritional experience contributes significantly to understanding the role of "energy food" in the struggle against protein malnutrition and hunger. The author has outlined the implications for the developing countries.

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

NASA Astrophysics Data System (ADS)

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 hold others accountable and demonstrate a rational disposition to realize mutual understanding on factual and normative validity claims. By demonstrating a rational disposition to practice autonomy and freedom in realizing mutual understanding on contested validity claims within the lifeworld of the university, public intellectuals realize a capacity for extending the regulative ideal of practicing public reason within the university into the constitution and regulation of public spaces for practicing public reason in the lifeworld of society.

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

DTIC Science & Technology

2008-01-01

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

Rational Design of Mouse Models for Cancer Research.

PubMed

Landgraf, Marietta; McGovern, Jacqui A; Friedl, Peter; Hutmacher, Dietmar W

2018-03-01

The laboratory mouse is widely considered as a valid and affordable model organism to study human disease. Attempts to improve the relevance of murine models for the investigation of human pathologies led to the development of various genetically engineered, xenograft and humanized mouse models. Nevertheless, most preclinical studies in mice suffer from insufficient predictive value when compared with cancer biology and therapy response of human patients. We propose an innovative strategy to improve the predictive power of preclinical cancer models. Combining (i) genomic, tissue engineering and regenerative medicine approaches for rational design of mouse models with (ii) rapid prototyping and computational benchmarking against human clinical data will enable fast and nonbiased validation of newly generated models. Copyright © 2017 Elsevier Ltd. All rights reserved.

Should Quality School Education Be a Kaizen (Improvement) or an Innovation?

ERIC Educational Resources Information Center

Sun-Keung Pang, Nicholas

1998-01-01

Reviews Hong Kong's School Management Initiative implementation strategies (rational-empirical, power-coercive, and normative-reeducative), compares them with New South Wales, Australia's strategies, and suggests an appropriate strategy for future reforms. In Australia, changes were radical and thorough (using power-coercive strategies), whereas…

Rational design of functional and tunable oscillating enzymatic networks

NASA Astrophysics Data System (ADS)

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.

Rational assignment of key motifs for function guides in silico enzyme identification.

PubMed

Höhne, Matthias; Schätzle, Sebastian; Jochens, Helge; Robins, Karen; Bornscheuer, Uwe T

2010-11-01

Biocatalysis has emerged as a powerful alternative to traditional chemistry, especially for asymmetric synthesis. One key requirement during process development is the discovery of a biocatalyst with an appropriate enantiopreference and enantioselectivity, which can be achieved, for instance, by protein engineering or screening of metagenome libraries. We have developed an in silico strategy for a sequence-based prediction of substrate specificity and enantiopreference. First, we used rational protein design to predict key amino acid substitutions that indicate the desired activity. Then, we searched protein databases for proteins already carrying these mutations instead of constructing the corresponding mutants in the laboratory. This methodology exploits the fact that naturally evolved proteins have undergone selection over millions of years, which has resulted in highly optimized catalysts. Using this in silico approach, we have discovered 17 (R)-selective amine transaminases, which catalyzed the synthesis of several (R)-amines with excellent optical purity up to >99% enantiomeric excess.

A Strategy for Understanding and Correcting Irrational Beliefs in Pupils: The Rational-Emotional Approach.

ERIC Educational Resources Information Center

Zionts, Paul

1983-01-01

Rational-emotive education integrates the cognitive, behavioral, and emotional aspects of personality and encourages behavior disordered students to discuss and work through their problems. Teachers need to display warmth, empathy, and be active-directive to help students manage their feelings and behaviors. (CL)

A Crosscultural Analysis of Argumentative Strategies in Student Essays.

ERIC Educational Resources Information Center

Kamimura, Taeko; Oi, Kyoko

A study of essays on a single topic (capital punishment) written by 22 American high school students and 30 second-year Japanese college students investigated: cultural differences in organizational patterns in argumentative essays; comparative use of rational and affective appeals; differences in content of rational and affective appeals;…

A rational design for hepatitis B virus X protein refolding and bioprocess development guided by second virial coefficient studies.

PubMed

Basu, Anindya; Chen, Wei Ning; Leong, Susanna Su Jan

2011-04-01

The hepatitis B virus X (HBx) protein is well known for its role in hepatitis B virus infection that often leads to hepatocellular carcinoma. Despite the clinical importance of HBx, there is little progress in anti-HBx drug development strategies due to shortage of HBx from native sources. Consistent expression of HBx as insoluble inclusion bodies within various expression systems has largely hindered HBx manufacturing via economical biosynthesis routes. Confronted by this roadblock, this study aims to quantitatively understand HBx protein behaviour in solution that will guide the rational development of a refolding-based bioprocess for HBx production. Second virial coefficient (SVC) measurements were employed to study the effects of varying physicochemical parameters on HBx intermolecular protein interaction. The SVC results suggest that covalent HBx aggregates play a key role in protein destabilisation during refolding. The use of an SVC-optimised refolding environment yielded bioactive and soluble HBx proteins from the denatured-reduced inclusion body state. This study provides new knowledge on HBx solubility behaviour in vitro, which is important in structure-function elucidation behaviour of this hydrophobic protein. Importantly, a rational refolding-based Escherichia coli bioprocess that can deliver purified and soluble HBx at large scale is successfully developed, which opens the way for rapid preparation of soluble HBx for further clinical and characterisation studies.

Stereoselectivity in N-Iminium Ion Cyclization: Development of an Efficient Synthesis of (±)-Cephalotaxine.

PubMed

Liu, Hao; Yu, Jing; Li, Xinyu; Yan, Rui; Xiao, Ji-Chang; Hong, Ran

2015-09-18

A stereoselective N-iminium ion cyclization with allylsilane to construct vicinal quaternary-tertiary carbon centers was developed for the concise synthesis of (±)-cephalotaxine. The current strategy features a TiCl4-promoted cyclization and ring-closure metathesis to furnish the spiro-ring system. The stereochemical outcome in the N-acyliminium ion cyclization was rationalized by the stereoelectronic effect of the Z- or E-allylsilane. Two diastereomers arising from the cyclization were merged into the formal synthesis of (±)-cephalotaxine.

[Investigation and protection for endangered Coptis deltoidea].

PubMed

Xiong, Feiyu; Ma, Yuntong; Yan, Zhuyun; Chen, Xin; Zhu, Meng; Chen, Run

2011-04-01

To investigate the history of the medicinal uses, resources, distribution, habitat and population characteristic of Coptis deltoidea, and provide basis for the protection and rational development and utilization of Radix Coptidis Deltoideae. The relevant literature and data was scrutinized and herbarium was compared, interview and field survey methods were carried out. The medicinal history, resources, distribution, population characteristic and protective strategy of C. deltoidea were summarized. The sustainable development of C. deltoidea was discussed. The resource is endangered, the germplasm resources should be intentionally protected and ensure the sustainable development and utilization of C. deltoidea.

[Guidance of FDA risk evaluation and mitigation strategy and enlightenment to drug risk management of post-marketing Chinese medicine].

PubMed

Li, Yuanyuan; Xie, Yanming

2011-10-01

The FDA risk evaluation and mitigation strategy (REMS) aims to drugs or biological products known or potential serious risk management. Analysis with the example of the content of the Onsolis REMS named FOCOS. Our country can be reference for the analysis of relevant experience and establish a scientific evaluation mechanism, strengthen the drug risk consciousness, promote the rational drug use, organic combined with the before-marketing and post-marketing evaluation of traditional Chinese medicine, and promote the evaluation of risk management of the drug development and improvement.

Asymmetric interaction paired with a super-rational strategy might resolve the tragedy of the commons without requiring recognition or negotiation.

PubMed

He, Jun-Zhou; Wang, Rui-Wu; Jensen, Christopher X J; Li, Yao-Tang

2015-01-14

Avoiding the tragedy of the commons requires that one or more individuals in a group or partnership "volunteer", benefiting the group at a cost to themselves. Recognition and negotiation with social partners can maintain cooperation, but are often not possible. If recognition and negotiation are not always the mechanism by which cooperative partnerships avoid collective tragedies, what might explain the diverse social cooperation observed in nature? Assuming that individuals interact asymmetrically and that both "weak" and "strong" players employ a super-rational strategy, we find that tragedy of the commons can be avoided without requiring either recognition or negotiation. Whereas in the volunteer's dilemma game a rational "strong" player is less likely to volunteer to provide a common good in larger groups, we show that under a wide range of conditions a super-rational "strong" player is more likely to provide a common good. These results imply that the integration of super-rationality and asymmetric interaction might have the potential to resolve the tragedy of the commons. By illuminating the conditions under which players are likely to volunteer, we shed light on the patterns of volunteerism observed in variety of well-studied cooperative social systems, and explore how societies might avert social tragedies.

Asymmetric interaction paired with a super-rational strategy might resolve the tragedy of the commons without requiring recognition or negotiation

PubMed Central

He, Jun-Zhou; Wang, Rui-Wu; Jensen, Christopher X. J.; Li, Yao-Tang

2015-01-01

Avoiding the tragedy of the commons requires that one or more individuals in a group or partnership “volunteer”, benefiting the group at a cost to themselves. Recognition and negotiation with social partners can maintain cooperation, but are often not possible. If recognition and negotiation are not always the mechanism by which cooperative partnerships avoid collective tragedies, what might explain the diverse social cooperation observed in nature? Assuming that individuals interact asymmetrically and that both “weak” and “strong” players employ a super-rational strategy, we find that tragedy of the commons can be avoided without requiring either recognition or negotiation. Whereas in the volunteer's dilemma game a rational “strong” player is less likely to volunteer to provide a common good in larger groups, we show that under a wide range of conditions a super-rational “strong” player is more likely to provide a common good. These results imply that the integration of super-rationality and asymmetric interaction might have the potential to resolve the tragedy of the commons. By illuminating the conditions under which players are likely to volunteer, we shed light on the patterns of volunteerism observed in variety of well-studied cooperative social systems, and explore how societies might avert social tragedies. PMID:25586876

Asymmetric interaction paired with a super-rational strategy might resolve the tragedy of the commons without requiring recognition or negotiation

NASA Astrophysics Data System (ADS)

He, Jun-Zhou; Wang, Rui-Wu; Jensen, Christopher X. J.; Li, Yao-Tang

2015-01-01

Avoiding the tragedy of the commons requires that one or more individuals in a group or partnership ``volunteer'', benefiting the group at a cost to themselves. Recognition and negotiation with social partners can maintain cooperation, but are often not possible. If recognition and negotiation are not always the mechanism by which cooperative partnerships avoid collective tragedies, what might explain the diverse social cooperation observed in nature? Assuming that individuals interact asymmetrically and that both ``weak'' and ``strong'' players employ a super-rational strategy, we find that tragedy of the commons can be avoided without requiring either recognition or negotiation. Whereas in the volunteer's dilemma game a rational ``strong'' player is less likely to volunteer to provide a common good in larger groups, we show that under a wide range of conditions a super-rational ``strong'' player is more likely to provide a common good. These results imply that the integration of super-rationality and asymmetric interaction might have the potential to resolve the tragedy of the commons. By illuminating the conditions under which players are likely to volunteer, we shed light on the patterns of volunteerism observed in variety of well-studied cooperative social systems, and explore how societies might avert social tragedies.

Rational Variability in Children's Causal Inferences: The Sampling Hypothesis

ERIC Educational Resources Information Center

Denison, Stephanie; Bonawitz, Elizabeth; Gopnik, Alison; Griffiths, Thomas L.

2013-01-01

We present a proposal--"The Sampling Hypothesis"--suggesting that the variability in young children's responses may be part of a rational strategy for inductive inference. In particular, we argue that young learners may be randomly sampling from the set of possible hypotheses that explain the observed data, producing different hypotheses with…

Intentional modulation of the late positive potential in response to smoking cues by cognitive strategies in smokers.

PubMed

Littel, Marianne; Franken, Ingmar H A

2011-01-01

Attentional bias is considered an important concept in addiction since it has been found to correlate with subjective craving and is strongly associated with relapse after periods of abstinence. Hence, investigating in ways to regulate attention for drug cues would be of major clinical relevance. The present study examined deliberate, cognitive modulation of motivated attention for smoking cues in smokers. The effects of three different reappraisal strategies on an electrophysiological measure of attentive processing were investigated. Early and late LPP components in response to passively viewed neutral and smoking pictures were compared with LPPs in response to smoking pictures that were reappraised with three different reappraisal strategies. Results show that when smokers actively imagine how pleasant it would be to smoke (pleasant condition), their early LPP in response to smoking cues increases, but when smokers actively focus on an alternative stimulus (distraction condition) or think of a rational, uninvolved interpretation of the situation (rational condition), smoking-related late LPP amplitude decreases to the processing level of neutral stimuli. Present results are the first to indicate that smoking cue-elicited LPP amplitudes can be modulated by cognitive strategies, suggesting that attentive processing of smoking cues can be intentionally regulated by smokers with various levels of dependence. Although cognitive strategies can lead to enhanced processing of smoking cues, it is not completely clear whether cognitive strategies are also successful in reducing smoking-related motivated attention. Although findings do point in this direction, present study is best considered preliminary and a starting point for other research on this topic. A focus on the distraction strategy is proposed, as there are indications that this strategy is more successful than the rational strategy in decreasing LPP amplitude.

Analgesic Prodrugs for Combating their Side-Effects: Rational Approach.

PubMed

Ruchita; Sucheta; Nanda, Sanju; Pathak, Dharampal

2017-01-01

Analgesics are the drugs which bring insensibility to pain without loosing consciousness. Treatment strategy is generally based on the type of pain. Most of the analgesics are associated with serious side effects, such as NSAIDS can cause severe GI disturbance and opioids can cause addiction. There are various ways to reduce their side effects The analgesic prodrug approach is one of the several strategies used to attain the required pharmacological response with a considerable decrease in side effects. The aim of this paper is to introduce in depth the rational behind the use of the analgesic prodrug approach from past to present. Data is collected from online as well as from extensive literature survey which have appeared on this subject during the last decades. This review will map the origins and development of the most important of the analgesic prodrugs to date. This review indicates that, designing analgesic prodrugs represent successful strategy to gain the required pharmacological activity with a considerable decrease in side effects. However thorough knowledge of diverse biological phenomena is needed which enables scientists to invent and design superior, nontoxic and better-targeted prodrugs. The newly synthesized chemical entity or prodrugs may or may not have intrinsic pharmacological activity and also synthesizing novel molecules consume a lot of time and money than developing prodrugs of existing clinically used analgesic drugs which is surely an attractive and promising area of research now a days. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Oman India Pipeline: An operational repair strategy based on a rational assessment of risk

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

German, P.

1996-12-31

This paper describes the development of a repair strategy for the operational phase of the Oman India Pipeline based upon the probability and consequences of a pipeline failure. Risk analyses and cost benefit analyses performed provide guidance on the level of deepwater repair development effort appropriate for the Oman India Pipeline project and identifies critical areas toward which more intense development effort should be directed. The risk analysis results indicate that the likelihood of a failure of the Oman India Pipeline during its 40-year life is low. Furthermore, the probability of operational failure of the pipeline in deepwater regions ismore » extremely low, the major proportion of operational failure risk being associated with the shallow water regions.« less

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

PubMed Central

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

2008-01-01

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

Effects of rational emotive behavior therapy for senior nursing students on coping strategies and self-efficacy.

PubMed

Kim, Myung Ah; Kim, Jiyoung; Kim, Eun Jung

2015-03-01

Senior nursing students are faced with various types of stressful events such as taking the national licensure exam or finding employment. Such stress can generate maladaptive behaviors as well as physical and psychological symptoms. There is evidence supporting the use of rational emotive behavior therapy (REBT) for reducing disruptive behaviors and negative emotions as well as improving self-efficacy and stress-coping strategies. The purpose of this study is to examine the effects of rational emotive behavior therapy (REBT) on stress coping strategies and self-efficacy for senior nursing students. Thirty-four senior nursing students in a nursing college were assigned randomly to an experimental group (n=18) and a control group (n=16). The REBT program consisted of 8 sessions, and it was implemented for a 4-week period. Outcome measures assessed stress-coping strategies and self-efficacy before and after intervention. After intervention with REBT, the mean difference scores for self-efficacy (p=.032) were significantly higher in the experimental group than in the control group. However, the mean difference scores for seeking social support (p=.166), problem solving (p=.126), and avoidance (p=.154) in stress-coping strategies were not significantly different between the two groups. The results imply that group counseling based on REBT enhances the self-efficacy among senior nursing students before graduation. As regards stress coping strategies, a longer intervention period is suggested. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

NASA Technical Reports Server (NTRS)

Thurman, S. W.

1990-01-01

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

Eutrophication of lakes and reservoirs: A framework for making management decisions

USGS Publications Warehouse

Rast, W.; Holland, M.

1988-01-01

The development of management strategies for the protection of environmental quality usually involves consideration both of technical and nontechnical issues. A logical, step-by-step framework for development of such strategies is provided. Its application to the control of cultured eutrophication of lakes and reservoirs illustrates its potential usefulness. From the perspective of the policymaker, the main consideration is that the eutrophication-related water quality of a lake or reservoir can be managed for given water uses. The approach presented here allows the rational assessment of relevant water-quality parameters and establishment of water-quality goals, consideration of social and other nontechnical issues, the possibilities of public involvement in the decision-making process, and a reasonable economic analysis within a management framework.

Rational Analyses of Information Foraging on the Web

ERIC Educational Resources Information Center

Pirolli, Peter

2005-01-01

This article describes rational analyses and cognitive models of Web users developed within information foraging theory. This is done by following the rational analysis methodology of (a) characterizing the problems posed by the environment, (b) developing rational analyses of behavioral solutions to those problems, and (c) developing cognitive…

Constraint-based modeling in microbial food biotechnology

PubMed Central

Rau, Martin H.

2018-01-01

Genome-scale metabolic network reconstruction offers a means to leverage the value of the exponentially growing genomics data and integrate it with other biological knowledge in a structured format. Constraint-based modeling (CBM) enables both the qualitative and quantitative analyses of the reconstructed networks. The rapid advancements in these areas can benefit both the industrial production of microbial food cultures and their application in food processing. CBM provides several avenues for improving our mechanistic understanding of physiology and genotype–phenotype relationships. This is essential for the rational improvement of industrial strains, which can further be facilitated through various model-guided strain design approaches. CBM of microbial communities offers a valuable tool for the rational design of defined food cultures, where it can catalyze hypothesis generation and provide unintuitive rationales for the development of enhanced community phenotypes and, consequently, novel or improved food products. In the industrial-scale production of microorganisms for food cultures, CBM may enable a knowledge-driven bioprocess optimization by rationally identifying strategies for growth and stability improvement. Through these applications, we believe that CBM can become a powerful tool for guiding the areas of strain development, culture development and process optimization in the production of food cultures. Nevertheless, in order to make the correct choice of the modeling framework for a particular application and to interpret model predictions in a biologically meaningful manner, one should be aware of the current limitations of CBM. PMID:29588387

Introducing management principles into the supply and distribution of medicines in Tunisia.

PubMed Central

Garraoui, A.; Le Feuvre, P.; Ledoux, M.

1999-01-01

A number of strategies have been proposed by various organizations and governments for rationalizing the use of drugs in developing countries. Such strategies include the use of essential drug lists, generic prescribing, and training in rational prescribing. None of these require doctors to become actively involved in the management of the drug supply to their health centres. In 1997, in the Kasserine region of Tunisia, the regional health authorities piloted a radically different strategy. This involved the theoretical allocation of a proportion of the regional drug budget to each district and subsequently to each health centre according to estimated demand. Medical staff were given responsibility for the management of these budgets, allowing them to control the nature and quantities of drugs supplied to the health centres in which they worked. This paper outlines the process by which this strategy was successfully implemented in the Foussana district of Kasserine region, and explores the problems encountered. It describes now the theoretical budgets were allocated to each district and how the costs of individual drugs and the consumption of drugs in the previous year were calculated. It then continues by giving an account of the training of the staff of the health centres, the preparation of a drug order form and the method of allocation of the theoretical budgets to each of the health centres. The results give an account of how the prescribing habits of doctors were changed as a result of the strategy, in order to take into account the costs of the drugs that they prescribed. They show how the health centres were able to manage their budgets, spending overall 99.8% of the budget allocated to the district. They outline some of the changes in the prescribing habits that took place, demonstrating a greater use of appropriate and essential drugs. The paper concludes that doctors and paramedical staff can successfully manage a theoretical drug budget, and that their involvement in this process leads to more rational prescribing within existing resource constraints. This has a consequence of benefiting patients, satisfying doctors and pleasing administrators. PMID:10427939

Pain Coping Strategies in Osteoarthritis Patients.

ERIC Educational Resources Information Center

Keefe, Francis J.; And Others

1987-01-01

Investigated the relation of pain coping strategies to pain, health status, and psychological distress in a group of osteoarthritis patients with chronic pain. Patients completed various questionnaires. Medical status variables were also used. The Pain Control and Rational Thinking factor derived from the Coping Strategies Questionnaire proved to…

Change in coping strategies following intensive intervention for special-service military personnel as civil emergency responders.

PubMed

Bian, Yongqiao; Xiong, Hongyan; Zhang, Lu; Tang, Tian; Liu, Zhen; Xu, Rufu; Lin, Hui; Xu, Bing

2011-01-01

To evaluate the effectiveness of a coping training program for the Chinese Special-Service Military Personnel (SSMP) as civil emergency responders. A parallel control trial was carried out in four special-service units (camps) stationed in Chongqing, China from Feb. 14th to May 30th, 2009. A total of 396 subjects were recruited and were randomly divided into an intervention group (n=201) and a control group (n=195) by clustering. Over the trial, participants in the intervention group received an additional coping-training program with 14 weekly two-hour sessions while the control group continued their normal work. Of all 396 participants, 343 attended all the sessions and completed the given measures. In comparison to their own scores in coping strategies at pre-intervention, significant and positive changes were observed in the intervention group (n=176) at post-intervention. Except for the strategy of self-blaming, the coping strategies including problem-solving, help-seeking, avoidance, fantasy and rationalization were improved. The descending order of the absolute change values over the trial in 5 coping strategies was fantasy, help-seeking, avoidance, problem-solving and rationalization. In addition, most subscales of social support and self-consistency, as powerful predictors of coping strategies, changed significantly over the intervention, while these changes were not observed in the control group (n=167). With the combined use of modular contents and procedural methods, our intervention not only led to fewer choices of immature coping strategies like fantasy, escape and rationalization, but also raised the use of mature coping strategies such as problem-solving and help-seeking. Accordingly, the intervention will be very helpful for regular coping training of Special-Service Units, something which can be verified and generalized for the whole SSMP in a future study.

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

ERIC Educational Resources Information Center

Sieber, Sam D.

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

Bounded rationality leads to equilibrium of public goods games.

PubMed

Xu, Zhaojin; Wang, Zhen; Zhang, Lianzhong

2009-12-01

In this work, we introduce a degree of rationality to the public goods games in which players can determine whether or not to participate, and with it a new mechanism has been established. Existence of the bounded rationality would lead to a new equilibrium which differs from the Nash equilibrium and qualitatively explains the fundamental role of loners' payoff for maintaining cooperation. Meanwhile, it is shown how the potential strategy influences the players' decision. Finally, we explicitly demonstrate a rock-scissors-paper dynamics which is a consequence of this model.

Bounded rationality leads to equilibrium of public goods games

NASA Astrophysics Data System (ADS)

Xu, Zhaojin; Wang, Zhen; Zhang, Lianzhong

2009-12-01

In this work, we introduce a degree of rationality to the public goods games in which players can determine whether or not to participate, and with it a new mechanism has been established. Existence of the bounded rationality would lead to a new equilibrium which differs from the Nash equilibrium and qualitatively explains the fundamental role of loners’ payoff for maintaining cooperation. Meanwhile, it is shown how the potential strategy influences the players’ decision. Finally, we explicitly demonstrate a rock-scissors-paper dynamics which is a consequence of this model.

Environmental Sustainability Analysis and Nutritional Strategies of Animal Production in China.

PubMed

Tan, Bie; Yin, Yulong

2017-02-08

Animal production in China has achieved considerable progress and contributes to 46% of the total agriculture output value of the country. However, this fast expansion of animal production has led to environmental pollution. In this article, we review the status of soil, water, and air pollution associated with animal production in China and analyze the main sources of the pollutants. The government has promulgated regulations and standards, and effective models and technologies have been developed to control pollution during the last 10 years. Because nutrition and feed strategies represent the most effective method of controlling environmental pollution at the source, this review focuses on nutritional technologies, including accurate feed formulation, rational use of additives, and proper processing of feeds. The advances of modern biotechnology and big data systems also provide more modern approaches to decreasing wastage release. These nutritional strategies are expected to promote sustainable development of animal production.

The formation of social reintegration strategies of the psychic suffering carrier: new directions for psychiatric nursing in Brazil.

PubMed

Souza, Emilia Jales Simões de; Moreira, Lilian Hortale de Oliveira; Cardoso, Maria Manuela Vila Nova; Ferreira, Rosa Gomes dos Santos; Silva, Thuany Cristine Santos da

2014-09-01

This is an exploratory and descriptive study of a qualitative nature. Its objective is to analyse the formation of strategies for social reintegration of the psychic suffering carrier in the practice of nurses working in hospital psychiatric institutions. For this study, we use, as a basis, the concepts and processes of the formation of strategies presented by Isabel Nicholau, 2001. Twelve nurses with health care experience in hospital psychiatric institutions participated in this study, and data collection occurred through semi-structured interviews in the year 2013. The data revealed that, in addition to human, material, and financial resources, institutional support is needed as is articulation and interaction among professionals and services. The importance of the social dimension and of the negotiation process depicts the development of conception of collective and integrated work. We conclude that strategies are emerging from the daily life of work and are not limited to a rational logic of cost and fundraising, but instead are developed through a negotiated process.

Promoter and Terminator Discovery and Engineering.

PubMed

Deaner, Matthew; Alper, Hal S

Control of gene expression is crucial to optimize metabolic pathways and synthetic gene networks. Promoters and terminators are stretches of DNA upstream and downstream (respectively) of genes that control both the rate at which the gene is transcribed and the rate at which mRNA is degraded. As a result, both of these elements control net protein expression from a synthetic construct. Thus, it is highly important to discover and engineer promoters and terminators with desired characteristics. This chapter highlights various approaches taken to catalogue these important synthetic elements. Specifically, early strategies have focused largely on semi-rational techniques such as saturation mutagenesis to diversify native promoters and terminators. Next, in an effort to reduce the length of the synthetic biology design cycle, efforts in the field have turned towards the rational design of synthetic promoters and terminators. In this vein, we cover recently developed methods such as hybrid engineering, high throughput characterization, and thermodynamic modeling which allow finer control in the rational design of novel promoters and terminators. Emphasis is placed on the methodologies used and this chapter showcases the utility of these methods across multiple host organisms.

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

PubMed

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

2017-02-01

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

From information processing to decisions: Formalizing and comparing psychologically plausible choice models.

PubMed

Heck, Daniel W; Hilbig, Benjamin E; Moshagen, Morten

2017-08-01

Decision strategies explain how people integrate multiple sources of information to make probabilistic inferences. In the past decade, increasingly sophisticated methods have been developed to determine which strategy explains decision behavior best. We extend these efforts to test psychologically more plausible models (i.e., strategies), including a new, probabilistic version of the take-the-best (TTB) heuristic that implements a rank order of error probabilities based on sequential processing. Within a coherent statistical framework, deterministic and probabilistic versions of TTB and other strategies can directly be compared using model selection by minimum description length or the Bayes factor. In an experiment with inferences from given information, only three of 104 participants were best described by the psychologically plausible, probabilistic version of TTB. Similar as in previous studies, most participants were classified as users of weighted-additive, a strategy that integrates all available information and approximates rational decisions. Copyright © 2017 Elsevier Inc. All rights reserved.

Rational combination strategies to enhance venetoclax activity and overcome resistance in hematologic malignancies.

PubMed

Grant, Steven

2018-06-01

Venetoclax (ABT-199) is a Bcl-2-specific BH3-mimetic that has shown significant promise in certain subtypes of CLL as well as in several other hematologic malignancies. As in the case of essentially all targeted agents, intrinsic or acquired resistance to this agent generally occurs, prompting the search for new strategies capable of circumventing this problem. A logical approach to this challenge involves rational combination strategies designed to disable preexisting or induced compensatory survival pathways. Many of these strategies involve downregulation of Mcl-1, a pro-survival Bcl-2 family member that is not targeted by venetoclax, and which often confers resistance to this agent. Given encouraging clinical results involving venetoclax in both lymphoid and myeloid malignancies, it is likely that such combination approaches will be incorporated into the therapeutic armamentarium for multiple hematologic malignancies in the near future.

Resource Planning for Massive Number of Process Instances

NASA Astrophysics Data System (ADS)

Xu, Jiajie; Liu, Chengfei; Zhao, Xiaohui

Resource allocation has been recognised as an important topic for business process execution. In this paper, we focus on planning resources for a massive number of process instances to meet the process requirements and cater for rational utilisation of resources before execution. After a motivating example, we present a model for planning resources for process instances. Then we design a set of heuristic rules that take both optimised planning at build time and instance dependencies at run time into account. Based on these rules we propose two strategies, one is called holistic and the other is called batched, for resource planning. Both strategies target a lower cost, however, the holistic strategy can achieve an earlier deadline while the batched strategy aims at rational use of resources. We discuss how to find balance between them in the paper with a comprehensive experimental study on these two approaches.

An effective rumor-containing strategy

NASA Astrophysics Data System (ADS)

Pan, Cheng; Yang, Lu-Xing; Yang, Xiaofan; Wu, Yingbo; Tang, Yuan Yan

2018-06-01

False rumors can lead to huge economic losses or/and social instability. Hence, mitigating the impact of bogus rumors is of primary importance. This paper focuses on the problem of how to suppress a false rumor by use of the truth. Based on a set of rational hypotheses and a novel rumor-truth mixed spreading model, the effectiveness and cost of a rumor-containing strategy are quantified, respectively. On this basis, the original problem is modeled as a constrained optimization problem (the RC model), in which the independent variable and the objective function represent a rumor-containing strategy and the effectiveness of a rumor-containing strategy, respectively. The goal of the optimization problem is to find the most effective rumor-containing strategy subject to a limited rumor-containing budget. Some optimal rumor-containing strategies are given by solving their respective RC models. The influence of different factors on the highest cost effectiveness of a RC model is illuminated through computer experiments. The results obtained are instructive to develop effective rumor-containing strategies.

Towards an understanding of the biology and targeted treatment of paediatric relapsed acute lymphoblastic leukaemia.

PubMed

Irving, Julie A E

2016-03-01

Acute lymphoblastic leukaemia is the most common childhood cancer and for those children who relapse, prognosis is poor and new therapeutic strategies are needed. Recurrent pathways implicated in relapse include RAS, JAK STAT, cell cycle, epigenetic regulation, B cell development, glucocorticoid response, nucleotide metabolism and DNA repair. Targeting these pathways is a rational therapeutic strategy and may deliver novel, targeted therapies into the clinic. Relapse often stems from a minor clone present at diagnosis and thus analysis of persisting leukaemia during upfront therapy may allow targeted drug intervention to prevent relapse. © 2015 John Wiley & Sons Ltd.

Cooperation, psychological game theory, and limitations of rationality in social interaction.

PubMed

Colman, Andrew M

2003-04-01

Rational choice theory enjoys unprecedented popularity and influence in the behavioral and social sciences, but it generates intractable problems when applied to socially interactive decisions. In individual decisions, instrumental rationality is defined in terms of expected utility maximization. This becomes problematic in interactive decisions, when individuals have only partial control over the outcomes, because expected utility maximization is undefined in the absence of assumptions about how the other participants will behave. Game theory therefore incorporates not only rationality but also common knowledge assumptions, enabling players to anticipate their co-players' strategies. Under these assumptions, disparate anomalies emerge. Instrumental rationality, conventionally interpreted, fails to explain intuitively obvious features of human interaction, yields predictions starkly at variance with experimental findings, and breaks down completely in certain cases. In particular, focal point selection in pure coordination games is inexplicable, though it is easily achieved in practice; the intuitively compelling payoff-dominance principle lacks rational justification; rationality in social dilemmas is self-defeating; a key solution concept for cooperative coalition games is frequently inapplicable; and rational choice in certain sequential games generates contradictions. In experiments, human players behave more cooperatively and receive higher payoffs than strict rationality would permit. Orthodox conceptions of rationality are evidently internally deficient and inadequate for explaining human interaction. Psychological game theory, based on nonstandard assumptions, is required to solve these problems, and some suggestions along these lines have already been put forward.

That's not funny! - But it should be: effects of humorous emotion regulation on emotional experience and memory.

PubMed

Kugler, Lisa; Kuhbandner, Christof

2015-01-01

Previous research has shown that humorous reappraisal can reduce elicited negative emotions, suggesting that humor may be a functional strategy to cope with emotionally negative situations. However, the effect of humorous reappraisal on later memory about the emotion-eliciting situation is currently unknown, although this is crucial for more adaptive responding in future situations. To address this issue, we examined the effects of humorous reappraisal on both emotional experience and memory, compared to non-humorous rational reappraisal and a non-reappraisal control condition. Replicating previous findings, humorous reappraisal reduced evoked negative valence and arousal levels very effectively, and the down-regulation of experienced negative emotions was even more pronounced after humorous compared to rational reappraisal. Regarding later memory for emotion-eliciting stimuli, both humorous and rational reappraisal reduced free recall, but recognition memory was unaffected, with memory strength being stronger after humorous than after rational reappraisal. These results indicate that humor seems to be indeed an optimal strategy to cope with negative situations because humor can help us to feel better when confronted with negative stimuli, but still allows us to retrieve stimulus information later when afforded to do so by the presence of appropriate contextual features.

TRPV1: A Target for Rational Drug Design

PubMed Central

Carnevale, Vincenzo; Rohacs, Tibor

2016-01-01

Transient Receptor Potential Vanilloid 1 (TRPV1) is a non-selective, Ca2+ permeable cation channel activated by noxious heat, and chemical ligands, such as capsaicin and resiniferatoxin (RTX). Many compounds have been developed that either activate or inhibit TRPV1, but none of them are in routine clinical practice. This review will discuss the rationale for antagonists and agonists of TRPV1 for pain relief and other conditions, and strategies to develop new, better drugs to target this ion channel, using the newly available high-resolution structures. PMID:27563913

Rational design and adaptive management of combination therapies for Hepatitis C virus infection

DOE PAGES

Ke, Ruian; Loverdo, Claude; Qi, Hangfei; ...

2015-06-30

Recent discoveries of direct acting antivirals against Hepatitis C virus (HCV) have raised hopes of effective treatment via combination therapies. Yet rapid evolution and high diversity of HCV populations, combined with the reality of suboptimal treatment adherence, make drug resistance a clinical and public health concern. We develop a general model incorporating viral dynamics and pharmacokinetics/ pharmacodynamics to assess how suboptimal adherence affects resistance development and clinical outcomes. We derive design principles and adaptive treatment strategies, identifying a high-risk period when missing doses is particularly risky for de novo resistance, and quantifying the number of additional doses needed to compensatemore » when doses are missed. Using data from large-scale resistance assays, we demonstrate that the risk of resistance can be reduced substantially by applying these principles to a combination therapy of daclatasvir and asunaprevir. By providing a mechanistic framework to link patient characteristics to the risk of resistance, these findings show the potential of rational treatment design.« less

Stress and Academic Performance in Dental Students: The Role of Coping Strategies and Examination-Related Self-Efficacy.

PubMed

Crego, Antonio; Carrillo-Diaz, María; Armfield, Jason M; Romero, Martín

2016-02-01

Academic stress negatively affects students' performance. However, little is known of the processes that may be involved in this association. This study aimed to analyze how other variables such as coping strategies and exam-related self-efficacy could be related to academic stress and performance for dental students. An online survey, including measures of coping strategies, perceived stress, exam-related self-efficacy, and academic performance, was completed by undergraduate dental students in Madrid, Spain. Of the 275 students invited to take the survey, 201 participated (response rate 73.6%). Rational coping strategies (problem-solving, positive reappraisal, seeking social support) were negatively associated with perceived stress (β=-0.25, p<0.01), whereas emotional coping strategies (venting negative emotions, negative auto-focus) were linked to increased academic stress (β=0.34, p<0.01). Moreover, rational and emotional coping strategies were, respectively, positively (β=0.16, p<0.05) and negatively (β=-0.22, p<0.01) associated with students' exam-related self-efficacy, and this relation was found to be partially mediated by the students' perceived stress (β=-0.30, p<0.01). Experiencing higher levels of stress during the examination period was found to be associated with poorer average grades (β=-0.21, p<0.01), but students' exam-related self-efficacy partially mediated this relation (β=0.23, p<0.01). Those students who perceived themselves as more efficient in completing examinations reported better grades. Using adequate coping strategies (i.e., rational coping) may help to reduce stress for dental students and, through their effect on exam-related self-efficacy appraisals, contribute to improved academic performance.

Group rationale, collective sense: beyond intergroup bias.

PubMed

Spears, Russell

2010-03-01

In this paper, I contest the view of the group as a source of bias and irrationality, especially prevalent within social psychology. I argue that this negative evaluation often arises by applying inappropriate standards, relating to the wrong level of analysis (often the individual level). Second, the image of the group as bad and biasing is often overstated. For example, the evidence suggests that intergroup discrimination, rather than being universal or generic, is often constrained, proportionate and reflects functional and rational strategies for managing threats and opportunities at the group level. Third, although the recent upsurge of interest in group emotions could be seen to reinforce the dualism between rationality and emotion, the contemporary functional approach argues for group emotions as augmenting rather than contradicting rationality. However, we should be wary (and weary) of narrow economic and individualist notions of rationality; group identity may offer the opportunity to redefine rationality in more collective and prosocial ways.

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

PubMed

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

2015-12-01

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

Strategic Genco offers in electric energy markets cleared by merit order

NASA Astrophysics Data System (ADS)

Hasan, Ebrahim A. Rahman

In an electricity market cleared by merit-order economic dispatch we identify necessary and sufficient conditions under which the market outcomes supported by pure strategy Nash equilibria (NE) exist when generating companies (Gencos) game through continuously variable incremental cost (IC) block offers. A Genco may own any number of units, each unit having multiple blocks with each block being offered at a constant IC. Next, a mixed-integer linear programming (MILP) scheme devoid of approximations or iterations is developed to identify all possible NE. The MILP scheme is systematic and general but computationally demanding for large systems. Thus, an alternative significantly faster lambda-iterative approach that does not require the use of MILP was also developed. Once all NE are found, one critical question is to identify the one whose corresponding gaming strategy may be considered by all Gencos as being the most rational. To answer this, this thesis proposes the use of a measure based on the potential profit gain and loss by each Genco for each NE. The most rational offer strategy for each Genco in terms of gaming or not gaming that best meets their risk/benefit expectations is the one corresponding to the NE with the largest gain to loss ratio. The computation of all NE is tested on several systems of up to ninety generating units, each with four incremental cost blocks. These NE are then used to examine how market power is influenced by market parameters, specifically, the number of competing Gencos, their size and true ICs, as well as the level of demand and price cap.

Synthetic Biological Approaches to Natural Product Biosynthesis

PubMed Central

Winter, Jaclyn M; Tang, Yi

2012-01-01

Small molecules produced in Nature continue to be an inspiration for the development of new therapeutic agents. These natural products possess exquisite chemical diversity, which gives rise to their wide range of biological activities. In their host organism, natural products are assembled and modified by dedicated biosynthetic pathways that Nature has meticulously developed. Often times, the complex structures or chemical modifications instated by these pathways are difficult to replicate using traditional synthetic methods. An alternative approach for creating or enhancing the structural variation of natural products is through combinatorial biosynthesis. By rationally reprogramming and manipulating the biosynthetic machinery responsible for their production, unnatural metabolites that were otherwise inaccessible can be obtained. Additionally, new chemical structures can be synthesized or derivatized by developing the enzymes that carry out these complicated chemical reactions into biocatalysts. In this review, we will discuss a variety of combinatorial biosynthetic strategies, their technical challenges, and highlight some recent (since 2007) examples of rationally designed unnatural metabolites, as well as platforms that have been established for the production and modification of clinically important pharmaceutical compounds. PMID:22221832

How High School Students Construct Decision-Making Strategies for Choosing Colleges

ERIC Educational Resources Information Center

Govan, George V.; Patrick, Sondra; Yen, Cherng-Jyn

2006-01-01

This study examined how high school seniors construct decision-making strategies for choosing a college to attend. To comprehend their decision-making strategies, we chose to examine this process through the theoretical lens of bounded rationality, which brings to light the complexity in constructing a college choice decision-making strategy…

Measurements of Rationality: Individual Differences in Information Processing, the Transitivity of Preferences and Decision Strategies

PubMed Central

Sleboda, Patrycja; Sokolowska, Joanna

2017-01-01

The first goal of this study was to validate the Rational-Experiential Inventory (REI) and the Cognitive Reflection Test (CRT) through checking their relation to the transitivity axiom. The second goal was to test the relation between decision strategies and cognitive style as well as the relation between decision strategies and the transitivity of preferences. The following characteristics of strategies were investigated: requirements for trade-offs, maximization vs. satisficing and option-wise vs. attribute-wise information processing. Respondents were given choices between two multi-attribute options. The options were designed so that the choice indicated which strategy was applied. Both the REI-R and the CRT were found to be good predictors of the transitivity of preferences. Respondents who applied compensatory strategies and the maximization criterion scored highly on the REI-R and in the CRT, whereas those who applied the satisficing rule scored highly on the REI-R but not in the CRT. Attribute-wise information processing was related to low scores in both measurements. Option-wise information processing led to a high transitivity of preferences. PMID:29093695

Measurements of Rationality: Individual Differences in Information Processing, the Transitivity of Preferences and Decision Strategies.

PubMed

Sleboda, Patrycja; Sokolowska, Joanna

2017-01-01

The first goal of this study was to validate the Rational-Experiential Inventory ( REI ) and the Cognitive Reflection Test ( CRT ) through checking their relation to the transitivity axiom. The second goal was to test the relation between decision strategies and cognitive style as well as the relation between decision strategies and the transitivity of preferences. The following characteristics of strategies were investigated: requirements for trade-offs, maximization vs. satisficing and option-wise vs. attribute-wise information processing. Respondents were given choices between two multi-attribute options. The options were designed so that the choice indicated which strategy was applied. Both the REI-R and the CRT were found to be good predictors of the transitivity of preferences. Respondents who applied compensatory strategies and the maximization criterion scored highly on the REI-R and in the CRT , whereas those who applied the satisficing rule scored highly on the REI-R but not in the CRT . Attribute-wise information processing was related to low scores in both measurements. Option-wise information processing led to a high transitivity of preferences.

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

DOE PAGES

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

2016-02-29

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

Structure and Ligand Based Drug Design Strategies in the Development of Novel 5-LOX Inhibitors

PubMed Central

Aparoy, Polamarasetty; Kumar Reddy, Kakularam; Reddanna, Pallu

2012-01-01

Lipoxygenases (LOXs) are non-heme iron containing dioxygenases involved in the oxygenation of polyunsaturated fatty acids (PUFAs) such as arachidonic acid (AA). Depending on the position of insertion of oxygen, LOXs are classified into 5-, 8-, 9-, 12- and 15-LOX. Among these, 5-LOX is the most predominant isoform associated with the formation of 5-hydroperoxyeicosatetraenoic acid (5-HpETE), the precursor of non-peptido (LTB4) and peptido (LTC4, LTD4, and LTE4) leukotrienes. LTs are involved in inflammatory and allergic diseases like asthma, ulcerative colitis, rhinitis and also in cancer. Consequently 5-LOX has become target for the development of therapeutic molecules for treatment of various inflammatory disorders. Zileuton is one such inhibitor of 5-LOX approved for the treatment of asthma. In the recent times, computer aided drug design (CADD) strategies have been applied successfully in drug development processes. A comprehensive review on structure based drug design strategies in the development of novel 5-LOX inhibitors is presented in this article. Since the crystal structure of 5-LOX has been recently solved, efforts to develop 5-LOX inhibitors have mostly relied on ligand based rational approaches. The present review provides a comprehensive survey on these strategies in the development of 5-LOX inhibitors. PMID:22680930

Decision-Making Styles and Problem-Solving Appraisal.

ERIC Educational Resources Information Center

Phillips, Susan D.; And Others

1984-01-01

Compared decision-making style and problem-solving appraisal in 243 undergraduates. Results suggested that individuals who employ rational decision-making strategies approach problematic situations, while individuals who endorse dependent decisional strategies approach problematic situations without confidence in their problem-solving abilities.…

Drug Policy and Rationality: An Exploration of the Research-Policy Interface in Ireland

ERIC Educational Resources Information Center

Randall, Niamh

2011-01-01

This article reports on a study which aimed to explore the extent to which drug policy making in Ireland might be deemed to be a rational, evidence-based process. The research was completed during the first half of 2008, as the National Drug Strategy 2001-2008--which explicitly claimed to have research as one of its main "pillars"--was…

Localized melt-scan strategy for site specific control of grain size and primary dendrite arm spacing in electron beam additive manufacturing

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

Raghavan, Narendran; Simunovic, Srdjan; Dehoff, Ryan

In addition to design geometry, surface roughness, and solid-state phase transformation, solidification microstructure plays a crucial role in controlling the performance of additively manufactured components. Crystallographic texture, primary dendrite arm spacing (PDAS), and grain size are directly correlated to local solidification conditions. We have developed a new melt-scan strategy for inducing site specific, on-demand control of solidification microstructure. We were able to induce variations in grain size (30 μm–150 μm) and PDAS (4 μm - 10 μm) in Inconel 718 parts produced by the electron beam additive manufacturing system (Arcam®). A conventional raster melt-scan resulted in a grain size ofmore » about 600 μm. The observed variations in grain size with different melt-scan strategies are rationalized using a numerical thermal and solidification model which accounts for the transient curvature of the melt pool and associated thermal gradients and liquid-solid interface velocities. The refinement in grain size at high cooling rates (>104 K/s) is also attributed to the potential heterogeneous nucleation of grains ahead of the epitaxially growing solidification front. The variation in PDAS is rationalized using a coupled numerical-theoretical model as a function of local solidification conditions (thermal gradient and liquid-solid interface velocity) of the melt pool.« less

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

PubMed

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

2017-02-01

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

ICU Admission, Discharge, and Triage Guidelines: A Framework to Enhance Clinical Operations, Development of Institutional Policies, and Further Research.

PubMed

Nates, Joseph L; Nunnally, Mark; Kleinpell, Ruth; Blosser, Sandralee; Goldner, Jonathan; Birriel, Barbara; Fowler, Clara S; Byrum, Diane; Miles, William Scherer; Bailey, Heatherlee; Sprung, Charles L

2016-08-01

To update the Society of Critical Care Medicine's guidelines for ICU admission, discharge, and triage, providing a framework for clinical practice, the development of institutional policies, and further research. An appointed Task Force followed a standard, systematic, and evidence-based approach in reviewing the literature to develop these guidelines. The assessment of the evidence and recommendations was based on the principles of the Grading of Recommendations Assessment, Development and Evaluation system. The general subject was addressed in sections: admission criteria and benefits of different levels of care, triage, discharge timing and strategies, use of outreach programs to supplement ICU care, quality assurance/improvement and metrics, nonbeneficial treatment in the ICU, and rationing considerations. The literature searches yielded 2,404 articles published from January 1998 to October 2013 for review. Following the appraisal of the literature, discussion, and consensus, recommendations were written. Although these are administrative guidelines, the subjects addressed encompass complex ethical and medico-legal aspects of patient care that affect daily clinical practice. A limited amount of high-quality evidence made it difficult to answer all the questions asked related to ICU admission, discharge, and triage. Despite these limitations, the members of the Task Force believe that these recommendations provide a comprehensive framework to guide practitioners in making informed decisions during the admission, discharge, and triage process as well as in resolving issues of nonbeneficial treatment and rationing. We need to further develop preventive strategies to reduce the burden of critical illness, educate our noncritical care colleagues about these interventions, and improve our outreach, developing early identification and intervention systems.

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

PubMed

Oyarzún, Patricio; Kobe, Bostjan

2016-03-03

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

Pancreatic cancer in 1988. Possibilities and probabilities.

PubMed Central

Warshaw, A L; Swanson, R S

1988-01-01

Pancreatic adenocarcinoma is increasing in frequency, generally grows without symptoms until late in its natural history, and presents many discouraging unresolved problems in management. This review analyzes the status of current modalities of diagnosis, staging, and treatment. The limitations of those methods are defined, and possible improvements and new directions are suggested. A strategy for a rational and humane approach to pancreatic cancer is developed with the goal of maximizing quality as well as quantity of life. PMID:2461172

Developing Critical Rationality as a Pedagogical Aim

ERIC Educational Resources Information Center

Winch, Christopher

2004-01-01

The development of a conception of critical pedagogy is itself an aspect of the development of critical rationality within late modern societies, closely connected with the role of education in developing critical rationality. The role of critique pervades all aspects of life: for people as citizens, workers and self-determining private…

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

PubMed

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.

Competent Reasoning with Rational Numbers.

ERIC Educational Resources Information Center

Smith, John P. III

1995-01-01

Analyzed students' reasoning with fractions. Found that skilled students applied strategies specifically tailored to restricted classes of fractions and produced reliable solutions with a minimum of computation effort. Results suggest that competent reasoning depends on a knowledge base that includes numerically specific and invented strategies,…

Inoculating against Pro-Plagiarism Justifications: Rational and Affective Strategies

ERIC Educational Resources Information Center

Compton, Josh; Pfau, Michael

2008-01-01

Student plagiarism continues to threaten academic integrity. This investigation assessed whether an inoculation message strategy could combat university plagiarism by protecting student attitudes against pro-plagiarism justification arguments. Additionally, we sought theoretical confirmation of previous findings on involvement and accessibility in…

Rational Deletion Cloze Processing Strategies: ESL and Native English.

ERIC Educational Resources Information Center

Markham, Paul L.

1987-01-01

Explores cloze sensitivity to global comprehension by means of retrospective interview techniques. No significant differences were found between English as a second language (ESL) college students (N=14) and native English-speaking students (N=14) in their processing strategies. (Author/CB)

A Qualitative Study on Coping Strategies among Women from Food Insecurity Households in Selangor and Negeri Sembilan.

PubMed

Norhasmah, S; Zalilah, M S; Mohd Nasir, M T; Kandiah, M; Asnarulkhadi, A S

2010-04-01

Understanding the experiences of household food insecurity is essential for better measurement and assessment of its nutritional, physical and psychological consequences. This qualitative study explored coping strategies and their perceived severity in relation to household food insecurity. Women (n=57; 20-50 years old) from rural and urban areas in Selangor and Negeri Sembilan participated in this study. These women were interviewed using a semi-structured questionnaire. The questionnaire was divided into two parts, that is, demographic and socio-economic information and women's experiences of coping with household food insecurity. Women were chosen since they were primarily responsible for food acquisition and preparation for the all household members. Thematic analysis was utilized in data analysis. Thematic analysis is a method for identifying, analysing and reporting patterns and themes of the qualitative data. Themes capture something important related to the study objectives and describe an integrating as well as relational idea from the data. Results showed that households displayed a variety of non-food related coping strategies and food-related coping strategies. Women's descriptions of non-food related coping strategies to food insecurity were categorised into five themes i.e. cloth purchasing behaviors, reduce school-going children's expenditure, delay the payment of bills, adjust lifestyle and increase cash and income earning. Food related coping strategies were categorised into four themes i.e. food stretching, food rationing, food seeking and food anxiety. Food stretching is a strategy of food insecurity that affects the quality of diet. Food rationing comprises coping strategies of food insecurity related to the quantity of food available for household's consumption. Food seeking is a strategy of acquiring food through socially unacceptable ways and food anxiety is a strategy that indicates households allocating money to buy staple food in order to prevent food insecurity. Each coping strategy showed a different level of perceived severity, that is, less severe, quite severe, severe and very severe. In conclusion, the qualitative data provide valuable information for understanding the experiences of food insecurity that can be used as a basis to develop direct indicators that can capture the core behaviours and their level of severity to measure household food insecurity.

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

PubMed Central

Van Regenmortel, Marc H. V.

2018-01-01

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

Generic medicines policies in the Asia Pacific region: ways forward.

PubMed

Nguyen, Tuan A; Hassali, Mohamed A A; McLachlan, Andrew

2013-01-01

Generic medicines are a key strategy used by governments and third-party payers to contain medicines costs and improve the access to essential medicines. This strategy represents an important opportunity provided by the global intellectual property regimes to discover and develop copies of original products marketed by innovator companies once the patent protection term is over. While there is an extensive experience regarding generic medicines policies in developed countries, this evidence may not translate to developing countries. The generic medicines policies workshop at the Asia Pacific Conference on National Medicines Policies 2012 provided an important opportunity to discuss and document country-specific initiatives for improving access to and the rational of use of generic medicines in the Asia Pacific region. Based on the identified barriers and enablers to implementation of generic medicines policies in the region, a set of future action plans and recommendations has been made.

Rational behavior is a ‘double-edged sword’ when considering voluntary vaccination

NASA Astrophysics Data System (ADS)

Zhang, Haifeng; Fu, Feng; Zhang, Wenyao; Wang, Binghong

2012-10-01

Of particular importance for public health is how to understand strategic vaccination behavior in social networks. Social learning is a central aspect of human behavior, and it thus shapes vaccination individuals’ decision-making. Here, we study two simple models to address the impact of the more rational decision-making of individuals on voluntary vaccination. In the first model, individuals are endowed with memory capacity for their past experiences of dealing with vaccination. In addition to their current payoffs, they also take account of the historical payoffs that are discounted by a memory-decaying factor. They use such overall payoffs (weighing the current payoffs and historical payoffs) to reassess their vaccination strategies. Those who have higher overall payoffs are more likely imitated by their social neighbors. In the second model, individuals do not blindly learn the strategies of neighbors; they also combine the fraction of infection in the past epidemic season. If the fraction of infection surpasses the perceived risk threshold, individuals will increase the probability of taking vaccination. Otherwise, they will decrease the probability of taking vaccination. Then we use evolutionary game theory to study the vaccination behavior of people during an epidemiological process. To do this, we propose a two-stage model: individuals make vaccination decisions during a yearly vaccination campaign, followed by an epidemic season. This forms a feedback loop between the vaccination decisions of individuals and their health outcomes, and thus payoffs. We find that the two more rational decision-making models have nontrivial impacts on the vaccination behavior of individuals, and, as a result, on the final fraction of infection. Our results highlight that, from an individual’s viewpoint, the decisions are optimal and more rational. However, from the social viewpoint, the strategies of individuals can give rise to distinct outcomes. Namely, the rational behavior of individuals plays a ‘double-edged-sword’ role on the social effects.

Neural Underpinnings of Decision Strategy Selection: A Review and a Theoretical Model.

PubMed

Wichary, Szymon; Smolen, Tomasz

2016-01-01

In multi-attribute choice, decision makers use decision strategies to arrive at the final choice. What are the neural mechanisms underlying decision strategy selection? The first goal of this paper is to provide a literature review on the neural underpinnings and cognitive models of decision strategy selection and thus set the stage for a neurocognitive model of this process. The second goal is to outline such a unifying, mechanistic model that can explain the impact of noncognitive factors (e.g., affect, stress) on strategy selection. To this end, we review the evidence for the factors influencing strategy selection, the neural basis of strategy use and the cognitive models of this process. We also present the Bottom-Up Model of Strategy Selection (BUMSS). The model assumes that the use of the rational Weighted Additive strategy and the boundedly rational heuristic Take The Best can be explained by one unifying, neurophysiologically plausible mechanism, based on the interaction of the frontoparietal network, orbitofrontal cortex, anterior cingulate cortex and the brainstem nucleus locus coeruleus. According to BUMSS, there are three processes that form the bottom-up mechanism of decision strategy selection and lead to the final choice: (1) cue weight computation, (2) gain modulation, and (3) weighted additive evaluation of alternatives. We discuss how these processes might be implemented in the brain, and how this knowledge allows us to formulate novel predictions linking strategy use and neural signals.

Slow Invariant Manifolds in Chemically Reactive Systems

NASA Astrophysics Data System (ADS)

Paolucci, Samuel; Powers, Joseph M.

2006-11-01

The scientific design of practical gas phase combustion devices has come to rely on the use of mathematical models which include detailed chemical kinetics. Such models intrinsically admit a wide range of scales which renders their accurate numerical approximation difficult. Over the past decade, rational strategies, such as Intrinsic Low Dimensional Manifolds (ILDM) or Computational Singular Perturbations (CSP), for equilibrating fast time scale events have been successfully developed, though their computation can be challenging and their accuracy in most cases uncertain. Both are approximations to the preferable slow invariant manifold which best describes how the system evolves in the long time limit. Strategies for computing the slow invariant manifold are examined, and results are presented for practical combustion systems.

That’s not funny! – But it should be: effects of humorous emotion regulation on emotional experience and memory

PubMed Central

Kugler, Lisa; Kuhbandner, Christof

2015-01-01

Previous research has shown that humorous reappraisal can reduce elicited negative emotions, suggesting that humor may be a functional strategy to cope with emotionally negative situations. However, the effect of humorous reappraisal on later memory about the emotion-eliciting situation is currently unknown, although this is crucial for more adaptive responding in future situations. To address this issue, we examined the effects of humorous reappraisal on both emotional experience and memory, compared to non-humorous rational reappraisal and a non-reappraisal control condition. Replicating previous findings, humorous reappraisal reduced evoked negative valence and arousal levels very effectively, and the down-regulation of experienced negative emotions was even more pronounced after humorous compared to rational reappraisal. Regarding later memory for emotion-eliciting stimuli, both humorous and rational reappraisal reduced free recall, but recognition memory was unaffected, with memory strength being stronger after humorous than after rational reappraisal. These results indicate that humor seems to be indeed an optimal strategy to cope with negative situations because humor can help us to feel better when confronted with negative stimuli, but still allows us to retrieve stimulus information later when afforded to do so by the presence of appropriate contextual features. PMID:26379608

Rational suicide among patients who are terminally ill.

PubMed

Valente, S M; Trainor, D

1998-08-01

Patients' end-of-life decisions challenge nurses. Often, aggressive, life prolonging strategies create ethical dilemmas for nurses when patients decide to stop treatment. In Oregon, assisted suicide is legal and will have a profound effect on nursing practice. When a patient considers suicide, nurses need to examine the patient's mental health, symptom management, and rational decision-making ability. Evaluation of suicide risk is a priority. Nurses need to recognize that medical land psychological symptoms often trigger thoughts of suicide, but prompt treatment of pain and symptoms also reduces suicide risk. Ethical issues and guidelines for management of patients considering suicide and evaluation of rationality are presented.

Student’s Critical Thinking in Solving Open-Ended Problems Based on Their Personality Type

NASA Astrophysics Data System (ADS)

Fitriana, L. D.; Fuad, Y.; Ekawati, R.

2018-01-01

Critical thinking plays an important role for students in solving open-ended problems. This research aims at describing student’s critical thinking in solving open-ended problems based on Keirsey’s personality types, namely rational, idealist, guardian, and artisan. Four students, with the higher rank in the mathematics’ test and representing each type of Keirsey personality, were selected as the research subjects. The data were collected from the geometry problem and interviews. The student’s critical thinking is described based on the FRISCO criteria. The result underlines that rational and idealist students fulfilled all FRISCO criteria, and but not for guardian and artisan students. Related to the inference criteria, guardian and artisan students could not make reasonable conclusions and connect the concepts. Related to the reason of criteria, rational student performed critical thinking by providing logical reason that supported his strategy to solve the problem. In contrast, the idealist student provided subjective reason. This results suggest that teachers should frequently train the students’ logical thinkingin every lesson and activity to develop student’s critical thinking and take the student’s personality character into account, especially for guardian and artisan students.

An evolutionarily stable strategy and the critical point of hog futures trading entities based on replicator dynamic theory: 2006–2015 data for China’s 22 provinces

PubMed Central

Pang, Jinbo; Deng, Lingfei

2017-01-01

Although frequent fluctuations in domestic hog prices seriously affect the stability and robustness of the hog supply chain, hog futures (an effective hedging instrument) have not been listed in China. To better understand hog futures market hedging, it is important to study the steady state of intersubjective bidding. This paper uses evolutionary game theory to construct a game model between hedgers and speculators in the hog futures market, and replicator dynamic equations are then used to obtain the steady state between the two trading entities. The results show that the steady state is one in which hedgers adopt a “buy” strategy and speculators adopt a “do not speculate” strategy, but this type of extreme steady state is not easily realized. Thus, to explore the rational proportion of hedgers and speculators in the evolutionary stabilization strategy, bidding processes were simulated using weekly average hog prices from 2006 to 2015, such that the conditions under which hedgers and speculators achieve a steady state could be analyzed. This task was performed to achieve the stability critical point, and we show that only when the value of λ is satisfied and the conditions of hog futures price changes and futures price are satisfied can hedgers and speculators achieve a rational proportion and a stable hog futures market. This market can thus provide a valuable reference for the development of the Chinese hog futures market and the formulation and guidance of relevant departmental policies. PMID:28241024

An evolutionarily stable strategy and the critical point of hog futures trading entities based on replicator dynamic theory: 2006-2015 data for China's 22 provinces.

PubMed

Pang, Jinbo; Deng, Lingfei; Wang, Gangyi

2017-01-01

Although frequent fluctuations in domestic hog prices seriously affect the stability and robustness of the hog supply chain, hog futures (an effective hedging instrument) have not been listed in China. To better understand hog futures market hedging, it is important to study the steady state of intersubjective bidding. This paper uses evolutionary game theory to construct a game model between hedgers and speculators in the hog futures market, and replicator dynamic equations are then used to obtain the steady state between the two trading entities. The results show that the steady state is one in which hedgers adopt a "buy" strategy and speculators adopt a "do not speculate" strategy, but this type of extreme steady state is not easily realized. Thus, to explore the rational proportion of hedgers and speculators in the evolutionary stabilization strategy, bidding processes were simulated using weekly average hog prices from 2006 to 2015, such that the conditions under which hedgers and speculators achieve a steady state could be analyzed. This task was performed to achieve the stability critical point, and we show that only when the value of λ is satisfied and the conditions of hog futures price changes and futures price are satisfied can hedgers and speculators achieve a rational proportion and a stable hog futures market. This market can thus provide a valuable reference for the development of the Chinese hog futures market and the formulation and guidance of relevant departmental policies.

The Continuing Quest for Rationality in Curriculum Practice.

ERIC Educational Resources Information Center

Gay, Geneva

1979-01-01

Suggests that understanding different conceptual models of curriculum making will increase the effectiveness and rationality of the development process. Presents four commonly used models of curriculum development: empiricism, rationalism, pragmatism, and humanism. (Author/JM)

Advances in nanosized zeolites

NASA Astrophysics Data System (ADS)

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

2013-07-01

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

A framework for service enterprise workflow simulation with multi-agents cooperation

NASA Astrophysics Data System (ADS)

Tan, Wenan; Xu, Wei; Yang, Fujun; Xu, Lida; Jiang, Chuanqun

2013-11-01

Process dynamic modelling for service business is the key technique for Service-Oriented information systems and service business management, and the workflow model of business processes is the core part of service systems. Service business workflow simulation is the prevalent approach to be used for analysis of service business process dynamically. Generic method for service business workflow simulation is based on the discrete event queuing theory, which is lack of flexibility and scalability. In this paper, we propose a service workflow-oriented framework for the process simulation of service businesses using multi-agent cooperation to address the above issues. Social rationality of agent is introduced into the proposed framework. Adopting rationality as one social factor for decision-making strategies, a flexible scheduling for activity instances has been implemented. A system prototype has been developed to validate the proposed simulation framework through a business case study.

Parkinson's disease: no milk today?

PubMed

Kistner, Andrea; Krack, Paul

2014-01-01

Several prospective epidemiological studies on large cohorts have consistently reported an association between milk intake and a higher incidence of Parkinson's disease (PD). Pesticide contamination of milk and milk's urate-lowering effects have been put forward as risk factors to explain epidemiological data. This has led to considerable uncertainty among physicians and avoidance of dairy products by PD patients. However, neither factor stands up to the rational and detailed examination of the literature carried out in this mini-review. We suggest that changes in eating behavior related to pre-motor PD are an alternative potential explanation of correlations observed between milk intake and PD occurrence. Despite clear-cut associations between milk intake and PD incidence, there is no rational explanation for milk being a risk factor for PD. Based on current knowledge, limiting the consumption of dairy products does not seem to be a reasonable strategy in the prevention of the development and progression of PD.

Multi-target drugs: the trend of drug research and development.

PubMed

Lu, Jin-Jian; Pan, Wei; Hu, Yuan-Jia; Wang, Yi-Tao

2012-01-01

Summarizing the status of drugs in the market and examining the trend of drug research and development is important in drug discovery. In this study, we compared the drug targets and the market sales of the new molecular entities approved by the U.S. Food and Drug Administration from January 2000 to December 2009. Two networks, namely, the target-target and drug-drug networks, have been set up using the network analysis tools. The multi-target drugs have much more potential, as shown by the network visualization and the market trends. We discussed the possible reasons and proposed the rational strategies for drug research and development in the future.

Development of background-free tame fluorescent probes for intracellular live cell imaging

PubMed Central

Alamudi, Samira Husen; Satapathy, Rudrakanta; Kim, Jihyo; Su, Dongdong; Ren, Haiyan; Das, Rajkumar; Hu, Lingna; Alvarado-Martínez, Enrique; Lee, Jung Yeol; Hoppmann, Christian; Peña-Cabrera, Eduardo; Ha, Hyung-Ho; Park, Hee-Sung; Wang, Lei; Chang, Young-Tae

2016-01-01

Fluorescence labelling of an intracellular biomolecule in native living cells is a powerful strategy to achieve in-depth understanding of the biomolecule's roles and functions. Besides being nontoxic and specific, desirable labelling probes should be highly cell permeable without nonspecific interactions with other cellular components to warrant high signal-to-noise ratio. While it is critical, rational design for such probes is tricky. Here we report the first predictive model for cell permeable background-free probe development through optimized lipophilicity, water solubility and charged van der Waals surface area. The model was developed by utilizing high-throughput screening in combination with cheminformatics. We demonstrate its reliability by developing CO-1 and AzG-1, a cyclooctyne- and azide-containing BODIPY probe, respectively, which specifically label intracellular target organelles and engineered proteins with minimum background. The results provide an efficient strategy for development of background-free probes, referred to as ‘tame' probes, and novel tools for live cell intracellular imaging. PMID:27321135

Application of communications satellites to educational development. [technology utilization/information systems - bibliographies

NASA Technical Reports Server (NTRS)

Morgan, R. P.

1975-01-01

A summary of research is presented. The broad objectives of this interdisciplinary research effort were: (1) to assess the role of satellite communications as a means of improving education in the United States, as well as in less-developed areas of the world; (2) to generate basic knowledge which will aid in making rational decisions about satellite application in the field of education in the years ahead; (3) to devise systems and strategies for improving education; and (4) to educate individuals who will be knowledgeable about aspects of satellite communications policy which transcend any single discipline.

Community psychiatric care: from libertarianism to coercion. Moral panic and mental health policy in Britain.

PubMed

Holloway, F

1996-08-01

This article discusses recent developments in mental health policy in Britain, focusing on the move towards compulsory supervision of mentally ill people in the community. It is argued that the desire for compulsion reflects moral panic rather than rational appraisal of the undoubted problems with community mental health care. Alternative strategies involving education of the patient and cares, the deployment of psychological treatments of psychosis and an emphasis on the negotiation of treatment plans, are advocated.

Changing Conspiracy Beliefs through Rationality and Ridiculing.

PubMed

Orosz, Gábor; Krekó, Péter; Paskuj, Benedek; Tóth-Király, István; Bőthe, Beáta; Roland-Lévy, Christine

2016-01-01

Conspiracy theory (CT) beliefs can be harmful. How is it possible to reduce them effectively? Three reduction strategies were tested in an online experiment using general and well-known CT beliefs on a comprehensive randomly assigned Hungarian sample ( N = 813): exposing rational counter CT arguments, ridiculing those who hold CT beliefs, and empathizing with the targets of CT beliefs. Several relevant individual differences were measured. Rational and ridiculing arguments were effective in reducing CT, whereas empathizing with the targets of CTs had no effect. Individual differences played no role in CT reduction, but the perceived intelligence and competence of the individual who conveyed the CT belief-reduction information contributed to the success of the CT belief reduction. Rational arguments targeting the link between the object of belief and its characteristics appear to be an effective tool in fighting conspiracy theory beliefs.

New social tasks for cognitive psychology; or, new cognitive tasks for social psychology.

PubMed

Wettersten, John

2014-01-01

To elucidate how differing theories of rationality lead to differing practices, their social rules must be analyzed. This is true not merely in science but also in society at large. This analysis of social thinking requires both the identification of innate cognitive social psychological processes and explanations of their relations with differing rules of rational practice. These new tasks can enable social psychologists to contribute to the study of how social situations facilitate or inhibit rational practice and enable cognitive psychologists to improve social psychological theory. In contrast to dominant current research strategies, social and cognitive psychologists can integrate social studies of rational practices and their consequences with studies of underlying cognitive psychological processes. In this article I do not attempt to carry out these tasks but rather point to both their lack of recognition and their importance.

Non-oral dopaminergic therapies for Parkinson’s disease: current treatments and the future

PubMed Central

Ray Chaudhuri, K; Qamar, Mubasher A; Rajah, Thadshani; Loehrer, Philipp; Sauerbier, Anna; Odin, Per; Jenner, Peter

2016-01-01

Dysfunction of the gastrointestinal tract has now been recognized to affect all stages of Parkinson’s disease (PD). The consequences lead to problems with absorption of oral medication, erratic treatment response, as well as silent aspiration, which is one of the key risk factors in developing pneumonia. The issue is further complicated by other gut abnormalities, such as small intestinal bacterial overgrowth (SIBO) and an altered gut microbiota, which occur in PD with variable frequency. Clinically, these gastrointestinal abnormalities might be associated with symptoms such as nausea, early-morning “off”, and frequent motor and non-motor fluctuations. Therefore, non-oral therapies that avoid the gastrointestinal system seem a rational option to overcome the problems of oral therapies in PD. Hence, several non-oral strategies have now been actively investigated and developed. The transdermal rotigotine patch, infusion therapies with apomorphine, intrajejunal levodopa, and the apomorphine pen strategy are currently in clinical use with a few others in development. In this review, we discuss and summarize the most recent developments in this field with a focus on non-oral dopaminergic strategies (excluding surgical interventions such as deep brain stimulation) in development or to be licensed for management of PD. PMID:28725704

Defining the role of polyamines in colon carcinogenesis using mouse models

PubMed Central

Ignatenko, Natalia A.; Gerner, Eugene W.; Besselsen, David G.

2011-01-01

Genetics and diet are both considered important risk determinants for colorectal cancer, a leading cause of death in the US and worldwide. Genetically engineered mouse (GEM) models have made a significant contribution to the characterization of colorectal cancer risk factors. Reliable, reproducible, and clinically relevant animal models help in the identification of the molecular events associated with disease progression and in the development of effictive treatment strategies. This review is focused on the use of mouse models for studying the role of polyamines in colon carcinogenesis. We describe how the available mouse models of colon cancer such as the multiple intestinal neoplasia (Min) mice and knockout genetic models facilitate understanding of the role of polyamines in colon carcinogenesis and help in the development of a rational strategy for colon cancer chemoprevention. PMID:21712957

Moral Education: A Handbook for Teachers. Insights and Practical Strategies for Helping Adolescents to Become More Caring, Thoughtful, and Responsible Persons.

ERIC Educational Resources Information Center

Hall, Robert T.

This handbook contains background readings, teaching strategies, and units of study for teaching moral education at the elementary, secondary, and adult levels. It offers practical strategies and insights for helping adolescents become more caring, thoughtful, and responsible persons. The intent is to help young people make more rational decisions…

Psychosocial predictors of immune response following bone marrow transplantation.

PubMed

Pulgar, Ángeles; Garrido, Sergio; Alcalá, Antonio; Reyes del Paso, Gustavo A

2012-01-01

This study analyzed the relationship between some psychosocial variables (depression, anxiety, stress, coping strategies, social support, optimism, rationality, and need for harmony) and clinical parameters indicative of immunological response after bone marrow transplantation (BMT; day of engraftment, number of infections and hemoglobin level) while controlling for demographic variables (age, educative level, civil state, and time from cancer diagnosis). Thirty-one post BMT hematological cancer patients were evaluated. Results show that higher educative levels are associated to lower number of infections, while age is associated with a delay in the time of engraftment; coping strategies, specially redefinition of the situation, relaxation, stoicism and passivity, are positively associated with the three clinical indices; depression is positively associated to number of infections during the hospitalization period; and rationality is associated with lower hemoglobin levels. These results suggest that psychosocial variables, especially coping strategies, play an important role in determining the immunological response after BMT.

Evolutionary aspects of anxiety disorders.

PubMed

Price, John S

2003-09-01

DANGER AND HARM ARE AVOIDED BY STRATEGIC DECISIONS MADE AT ALL THREE LEVELS OF THE TRIUNE FOREBRAIN: rational (neomammalian), emotional (paleomammalian), and instinctive (reptilian). This applies also to potential harm from conspecifics, which leads to a choice between escalating and de-escalating strategies. Anxiety is a component of de-escalating strategies mediated by the paleomammalian and reptilian forebrains. When the neomammalian (rational) brain fails to deal with the threat of conspecific danger, these more primitive de-escalating strategies may be activated and may present as anxiety disorders. The capacity for concealment of anxiety and other forms of negative affect has also evolved, and excessive concealment may lead to psychopaihology by breaking the negative feedback loop of excessive motivation, leading to impaired performance, leading to signals of distress, and leading to reduced exhortation to succeed on the part of parents and teachers; this situation is illustrated by a model based on the Yerkes-Dodson law.

Evolutionary aspects of anxiety disorders

PubMed Central

Price, John S.

2003-01-01

Danger and harm are avoided by strategic decisions made at all three levels of the triune forebrain: rational (neomammalian), emotional (paleomammalian), and instinctive (reptilian). This applies also to potential harm from conspecifics, which leads to a choice between escalating and de-escalating strategies. Anxiety is a component of de-escalating strategies mediated by the paleomammalian and reptilian forebrains. When the neomammalian (rational) brain fails to deal with the threat of conspecific danger, these more primitive de-escalating strategies may be activated and may present as anxiety disorders. The capacity for concealment of anxiety and other forms of negative affect has also evolved, and excessive concealment may lead to psychopaihology by breaking the negative feedback loop of excessive motivation, leading to impaired performance, leading to signals of distress, and leading to reduced exhortation to succeed on the part of parents and teachers; this situation is illustrated by a model based on the Yerkes-Dodson law. PMID:22033473

The current status and trend of clinical pharmacology in developing countries

PubMed Central

2013-01-01

Background Several international forums for promoting clinical pharmacology in developing countries have been held since 1980, and several clinical pharmacology programmes targeting developing countries were instituted such that the status of clinical pharmacology in developing countries is not where it was 50 years ago. Therefore, a survey and an appraisal of the literature on the current status of clinical pharmacology in developing countries were undertaken with a hope that it would enable development of appropriate strategies for further promotion of clinical pharmacology in these countries. Methods First, nine determinants (or enabling factors) for running a successful clinical pharmacology programme were identified, i.e., disease burden, drug situation, economic growth, clinical pharmacology activities, recognition, human capital, government support, international collaboration, and support for traditional/alternative medicines. These factors were then evaluated with regard to their current status in the developing countries that responded to an electronic questionnaire, and their historical perspective, using the literature appraisal. From these, a projected trend was constructed with recommendations on the way forward. Results Clinical pharmacology services, research and teaching in developing countries have improved over the past 50 years with over 90% of countries having the appropriate policies for regulation and rational use of medicines in place. Unfortunately, policy implementation remains a challenge, owing to a worsening disease burden and drug situation, versus fewer clinical pharmacologists and other competing priorities for the national budgets. This has led to a preference for training ‘a physician clinical pharmacologist’ in programmes emphasizing local relevancy and for a shorter time, and the training of other professionals in therapeutics for endemic diseases (task shifting), as the most promising strategies of ensuring rational use of medicines. Conclusion Clinical pharmacology in developing countries is advancing in a different way to that in the developed world and continuing support for these efforts will go a long way in promoting improved health for all. PMID:24074056

Shikimic Acid Production in Escherichia coli: From Classical Metabolic Engineering Strategies to Omics Applied to Improve Its Production.

PubMed

Martínez, Juan Andrés; Bolívar, Francisco; Escalante, Adelfo

2015-01-01

Shikimic acid (SA) is an intermediate of the SA pathway that is present in bacteria and plants. SA has gained great interest because it is a precursor in the synthesis of the drug oseltamivir phosphate (OSF), an efficient inhibitor of the neuraminidase enzyme of diverse seasonal influenza viruses, the avian influenza virus H5N1, and the human influenza virus H1N1. For the purposes of OSF production, SA is extracted from the pods of Chinese star anise plants (Illicium spp.), yielding up to 17% of SA (dry basis content). The high demand for OSF necessary to manage a major influenza outbreak is not adequately met by industrial production using SA from plants sources. As the SA pathway is present in the model bacteria Escherichia coli, several "intuitive" metabolically engineered strains have been applied for its successful overproduction by biotechnological processes, resulting in strains producing up to 71 g/L of SA, with high conversion yields of up to 0.42 (mol SA/mol Glc), in both batch and fed-batch cultures using complex fermentation broths, including glucose as a carbon source and yeast extract. Global transcriptomic analyses have been performed in SA-producing strains, resulting in the identification of possible key target genes for the design of a rational strain improvement strategy. Because possible target genes are involved in the transport, catabolism, and interconversion of different carbon sources and metabolic intermediates outside the central carbon metabolism and SA pathways, as genes involved in diverse cellular stress responses, the development of rational cellular strain improvement strategies based on omics data constitutes a challenging task to improve SA production in currently overproducing engineered strains. In this review, we discuss the main metabolic engineering strategies that have been applied for the development of efficient SA-producing strains, as the perspective of omics analysis has focused on further strain improvement for the production of this valuable aromatic intermediate.

Shikimic Acid Production in Escherichia coli: From Classical Metabolic Engineering Strategies to Omics Applied to Improve Its Production

PubMed Central

Martínez, Juan Andrés; Bolívar, Francisco; Escalante, Adelfo

2015-01-01

Shikimic acid (SA) is an intermediate of the SA pathway that is present in bacteria and plants. SA has gained great interest because it is a precursor in the synthesis of the drug oseltamivir phosphate (OSF), an efficient inhibitor of the neuraminidase enzyme of diverse seasonal influenza viruses, the avian influenza virus H5N1, and the human influenza virus H1N1. For the purposes of OSF production, SA is extracted from the pods of Chinese star anise plants (Illicium spp.), yielding up to 17% of SA (dry basis content). The high demand for OSF necessary to manage a major influenza outbreak is not adequately met by industrial production using SA from plants sources. As the SA pathway is present in the model bacteria Escherichia coli, several “intuitive” metabolically engineered strains have been applied for its successful overproduction by biotechnological processes, resulting in strains producing up to 71 g/L of SA, with high conversion yields of up to 0.42 (mol SA/mol Glc), in both batch and fed-batch cultures using complex fermentation broths, including glucose as a carbon source and yeast extract. Global transcriptomic analyses have been performed in SA-producing strains, resulting in the identification of possible key target genes for the design of a rational strain improvement strategy. Because possible target genes are involved in the transport, catabolism, and interconversion of different carbon sources and metabolic intermediates outside the central carbon metabolism and SA pathways, as genes involved in diverse cellular stress responses, the development of rational cellular strain improvement strategies based on omics data constitutes a challenging task to improve SA production in currently overproducing engineered strains. In this review, we discuss the main metabolic engineering strategies that have been applied for the development of efficient SA-producing strains, as the perspective of omics analysis has focused on further strain improvement for the production of this valuable aromatic intermediate. PMID:26442259

Development of the Rational Behavior Inventory: Initial Validity and Reliability

ERIC Educational Resources Information Center

Shorkey, Clayton T.; Whiteman, Victor L.

1977-01-01

The results of initial validity and reliability studies on the Rational Behavior Inventory are presented. The instrument was developed to be used for assessment, treatment planning, and evaluation of clients by counselors who use Rational Emotive Therapy. (Author/JKS)

Argumentative Strategies in American and Japanese English.

ERIC Educational Resources Information Center

Kamimura, Taeko; Oi, Kyoko

1998-01-01

A study examined differences in argumentative strategies in Japanese and American English by analyzing English essays on capital punishment written by 22 American high school seniors and 30 Japanese college sophomores. Differences were found in the organizational patterns, content and use of rational appeals, preference for type of diction, and…

A Contingent Analysis of the Relationship between IS Implementation Strategies and IS Success.

ERIC Educational Resources Information Center

Kim, Sang-Hoon; Lee, Jinjoo

1991-01-01

Considers approaches to dealing with user attitudes toward newly implemented information systems (IS), and suggests that behavioral management strategies relevant to IS fall into three categories: (1) empirical/rational; (2) normative/reeducative; and (3) power/coercive, based on "planned change" theories. An integrative contingent model…

McJobs and Pieces of Flair: Linking McDonaldization to Alienating Work

ERIC Educational Resources Information Center

Treiber, Linda Ann

2013-01-01

This article offers strategies for teaching about rationality, bureaucracy, and social change using George Ritzer's "The McDonaldization of Society" and its ideas about efficiency, predictability, calculability, and control. Student learning is facilitated using a series of strategies: making the familiar strange, explaining…

Strategy of Daiichi Sankyo discovery research in oncology.

PubMed

Akahane, Kouichi; Hirokawa, Kazunori

2014-02-01

We would like to introduce Daiichi Sankyo's approach to developing cancer targeted medicines with special reference to the drug discovery strategy, global discovery activities and external research collaboration leading to generation of innovative drugs for cancer patients. We are developing 14 clinical projects for cancer treatment and three of them have been previously approved. These are mostly targeted for growth and survival signals of cancer cells. To overcome the drug resistance mechanism derived from the heterogeneous nature of cancer, we are developing selective inhibitors in three major clusters of signal pathways which may allow future rational combinations of oncology products. In addition to the main research facility in Japan, research sites in the EU and the USA provide us with different technical expertise and diversified ideas of drug discovery. To access novel drug targets, we are facilitating research collaboration with leading academia and successful cancer research scientists. In conclusion, we intend to focus more on developing innovative personalized medicines for better treatment of cancer.

Mitigation of reversible self-association and viscosity in a human IgG1 monoclonal antibody by rational, structure-guided Fv engineering

PubMed Central

Geoghegan, James C.; Fleming, Ryan; Damschroder, Melissa; Bishop, Steven M.; Sathish, Hasige A.; Esfandiary, Reza

2016-01-01

ABSTRACT Undesired solution behaviors such as reversible self-association (RSA), high viscosity, and liquid-liquid phase separation can introduce substantial challenges during development of monoclonal antibody formulations. Although a global mechanistic understanding of RSA (i.e., native and reversible protein-protein interactions) is sufficient to develop robust formulation controls, its mitigation via protein engineering requires knowledge of the sites of protein-protein interactions. In the study reported here, we coupled our previous hydrogen-deuterium exchange mass spectrometry findings with structural modeling and in vitro screening to identify the residues responsible for RSA of a model IgG1 monoclonal antibody (mAb-C), and rationally engineered variants with improved solution properties (i.e., reduced RSA and viscosity). Our data show that mutation of either solvent-exposed aromatic residues within the heavy and light chain variable regions or buried residues within the heavy chain/light chain interface can significantly mitigate RSA and viscosity by reducing the IgG's surface hydrophobicity. The engineering strategy described here highlights the utility of integrating complementary experimental and in silico methods to identify mutations that can improve developability, in particular, high concentration solution properties, of candidate therapeutic antibodies. PMID:27050875

Development of bright fluorescent quadracyclic adenine analogues: TDDFT-calculation supported rational design

NASA Astrophysics Data System (ADS)

Foller Larsen, Anders; Dumat, Blaise; Wranne, Moa S.; Lawson, Christopher P.; Preus, Søren; Bood, Mattias; Gradén, Henrik; Marcus Wilhelmsson, L.; Grøtli, Morten

2015-07-01

Fluorescent base analogues (FBAs) comprise a family of increasingly important molecules for the investigation of nucleic acid structure and dynamics. We recently reported the quantum chemical calculation supported development of four microenvironment sensitive analogues of the quadracyclic adenine (qA) scaffold, the qANs, with highly promising absorptive and fluorescence properties that were very well predicted by TDDFT calculations. Herein, we report on the efficient synthesis, experimental and theoretical characterization of nine novel quadracyclic adenine derivatives. The brightest derivative, 2-CNqA, displays a 13-fold increased brightness (ɛΦF = 4500) compared with the parent compound qA and has the additional benefit of being a virtually microenvironment-insensitive fluorophore, making it a suitable candidate for nucleic acid incorporation and use in quantitative FRET and anisotropy experiments. TDDFT calculations, conducted on the nine novel qAs a posteriori, successfully describe the relative fluorescence quantum yield and brightness of all qA derivatives. This observation suggests that the TDDFT-based rational design strategy may be employed for the development of bright fluorophores built up from a common scaffold to reduce the otherwise costly and time-consuming screening process usually required to obtain useful and bright FBAs.

Differential Rationality and Personal Development.

ERIC Educational Resources Information Center

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…

If You Want to Feel Better--Try Thinking Better.

ERIC Educational Resources Information Center

Rogers, George W., Jr.

This article briefly describes Rational Emotive or Rational Behavior Therapy. Some historical data is given regarding its developer, Dr. Albert Ellis, and his beliefs. In addition the following rational concepts are examined: (1) the anatomy of an emotion; (2) the characteristics of rational thoughts; and (3) the rational self-analysis of…

Investigating rate-limiting barriers to nanoscale nonviral gene transfer with nanobiophotonics

NASA Astrophysics Data System (ADS)

Chen, Hunter H.

Nucleic acids are a novel class of therapeutics poised to address many unmet clinical needs. Safe and efficient delivery remains a significant challenge that has delayed the realization of the full therapeutic potential of nucleic acids. Nanoscale nonviral vectors offer an attractive alternative to viral vectors as natural and synthetic polymers or polypeptides may be rationally designed to meet the unique demands of individual applications. A mechanistic understanding of cellular barriers is necessary to develop guidelines for designing custom gene carriers which are expected to greatly impact this delivery challenge. The work herein focused on the relationships among nanocomplex stability, intracellular trafficking and unpacking kinetics, and DNA degradation. Ultrasensitive nanosensors based on QD-FRET were developed to characterize the biophysical properties of nanocomplexes and study these rate-limiting steps. Quantitative image analysis enabled the distributions of the subpopulation of condensed or released DNA to be determined within the major cellular compartments encountered during gene transfer. The steady state stability and unpacking kinetics within these compartments were found to impact transgene expression, elucidating multiple design strategies to achieve efficient gene transfer. To address enzymatic barriers, a novel two-step QD-FRET nanosensor was developed to analyze unpacking and DNA degradation simultaneously, which has not been accomplished previously. Bioresponsive strategies such as disulfide crosslinking and thermosensitivity were evaluated by QD-FRET and quantitative compartmental analysis as case studies to determine appropriate design specifications for thiolated polymers and thermoresponsive polypeptides. Relevant nanobiophotonic tools were developed as a platform to study major rate-limiting barriers to nanomedicine and demonstrated the feasibility of using mechanistic information gained from these tools to guide the rational design of gene carriers and achieve the desired properties that enable efficient gene transfer.

Neural Underpinnings of Decision Strategy Selection: A Review and a Theoretical Model

PubMed Central

Wichary, Szymon; Smolen, Tomasz

2016-01-01

In multi-attribute choice, decision makers use decision strategies to arrive at the final choice. What are the neural mechanisms underlying decision strategy selection? The first goal of this paper is to provide a literature review on the neural underpinnings and cognitive models of decision strategy selection and thus set the stage for a neurocognitive model of this process. The second goal is to outline such a unifying, mechanistic model that can explain the impact of noncognitive factors (e.g., affect, stress) on strategy selection. To this end, we review the evidence for the factors influencing strategy selection, the neural basis of strategy use and the cognitive models of this process. We also present the Bottom-Up Model of Strategy Selection (BUMSS). The model assumes that the use of the rational Weighted Additive strategy and the boundedly rational heuristic Take The Best can be explained by one unifying, neurophysiologically plausible mechanism, based on the interaction of the frontoparietal network, orbitofrontal cortex, anterior cingulate cortex and the brainstem nucleus locus coeruleus. According to BUMSS, there are three processes that form the bottom-up mechanism of decision strategy selection and lead to the final choice: (1) cue weight computation, (2) gain modulation, and (3) weighted additive evaluation of alternatives. We discuss how these processes might be implemented in the brain, and how this knowledge allows us to formulate novel predictions linking strategy use and neural signals. PMID:27877103

A Population Model Evaluating the Consequences of the Evolution of Double-Resistance and Tradeoffs on the Benefits of Two-Drug Antibiotic Treatments

PubMed Central

Campbell, Ellsworth M.; Chao, Lin

2014-01-01

The evolution of antibiotic resistance in microbes poses one of the greatest challenges to the management of human health. Because addressing the problem experimentally has been difficult, research on strategies to slow the evolution of resistance through the rational use of antibiotics has resorted to mathematical and computational models. However, despite many advances, several questions remain unsettled. Here we present a population model for rational antibiotic usage by adding three key features that have been overlooked: 1) the maximization of the frequency of uninfected patients in the human population rather than the minimization of antibiotic resistance in the bacterial population, 2) the use of cocktails containing antibiotic pairs, and 3) the imposition of tradeoff constraints on bacterial resistance to multiple drugs. Because of tradeoffs, bacterial resistance does not evolve directionally and the system reaches an equilibrium state. When considering the equilibrium frequency of uninfected patients, both cycling and mixing improve upon single-drug treatment strategies. Mixing outperforms optimal cycling regimens. Cocktails further improve upon aforementioned strategies. Moreover, conditions that increase the population frequency of uninfected patients also increase the recovery rate of infected individual patients. Thus, a rational strategy does not necessarily result in a tragedy of the commons because benefits to the individual patient and general public are not in conflict. Our identification of cocktails as the best strategy when tradeoffs between multiple-resistance are operating could also be extended to other host-pathogen systems. Cocktails or other multiple-drug treatments are additionally attractive because they allow re-using antibiotics whose utility has been negated by the evolution of single resistance. PMID:24498003

Neural Signatures of Rational and Heuristic Choice Strategies: A Single Trial ERP Analysis.

PubMed

Wichary, Szymon; Magnuski, Mikołaj; Oleksy, Tomasz; Brzezicka, Aneta

2017-01-01

In multi-attribute choice, people use heuristics to simplify decision problems. We studied the use of heuristic and rational strategies and their electrophysiological correlates. Since previous work linked the P3 ERP component to attention and decision making, we were interested whether the amplitude of this component is associated with decision strategy use. To this end, we recorded EEG when participants performed a two-alternative choice task, where they could acquire decision cues in a sequential manner and use them to make choices. We classified participants' choices as consistent with a rational Weighted Additive rule (WADD) or a simple heuristic Take The Best (TTB). Participants differed in their preference for WADD and TTB. Using a permutation-based single trial approach, we analyzed EEG responses to consecutive decision cues and their relation to the individual strategy preference. The preference for WADD over TTB was associated with overall higher signal amplitudes to decision cues in the P3 time window. Moreover, the preference for WADD was associated with similar P3 amplitudes to consecutive cues, whereas the preference for TTB was associated with substantial decreases in P3 amplitudes to consecutive cues. We also found that the preference for TTB was associated with enhanced N1 component to cues that discriminated decision alternatives, suggesting very early attention allocation to such cues by TTB users. Our results suggest that preference for either WADD or TTB has an early neural signature reflecting differences in attentional weighting of decision cues. In light of recent findings and hypotheses regarding P3, we interpret these results as indicating the involvement of catecholamine arousal systems in shaping predecisional information processing and strategy selection.

Neural Signatures of Rational and Heuristic Choice Strategies: A Single Trial ERP Analysis

PubMed Central

Wichary, Szymon; Magnuski, Mikołaj; Oleksy, Tomasz; Brzezicka, Aneta

2017-01-01

In multi-attribute choice, people use heuristics to simplify decision problems. We studied the use of heuristic and rational strategies and their electrophysiological correlates. Since previous work linked the P3 ERP component to attention and decision making, we were interested whether the amplitude of this component is associated with decision strategy use. To this end, we recorded EEG when participants performed a two-alternative choice task, where they could acquire decision cues in a sequential manner and use them to make choices. We classified participants’ choices as consistent with a rational Weighted Additive rule (WADD) or a simple heuristic Take The Best (TTB). Participants differed in their preference for WADD and TTB. Using a permutation-based single trial approach, we analyzed EEG responses to consecutive decision cues and their relation to the individual strategy preference. The preference for WADD over TTB was associated with overall higher signal amplitudes to decision cues in the P3 time window. Moreover, the preference for WADD was associated with similar P3 amplitudes to consecutive cues, whereas the preference for TTB was associated with substantial decreases in P3 amplitudes to consecutive cues. We also found that the preference for TTB was associated with enhanced N1 component to cues that discriminated decision alternatives, suggesting very early attention allocation to such cues by TTB users. Our results suggest that preference for either WADD or TTB has an early neural signature reflecting differences in attentional weighting of decision cues. In light of recent findings and hypotheses regarding P3, we interpret these results as indicating the involvement of catecholamine arousal systems in shaping predecisional information processing and strategy selection. PMID:28867996

A population model evaluating the consequences of the evolution of double-resistance and tradeoffs on the benefits of two-drug antibiotic treatments.

PubMed

Campbell, Ellsworth M; Chao, Lin

2014-01-01

The evolution of antibiotic resistance in microbes poses one of the greatest challenges to the management of human health. Because addressing the problem experimentally has been difficult, research on strategies to slow the evolution of resistance through the rational use of antibiotics has resorted to mathematical and computational models. However, despite many advances, several questions remain unsettled. Here we present a population model for rational antibiotic usage by adding three key features that have been overlooked: 1) the maximization of the frequency of uninfected patients in the human population rather than the minimization of antibiotic resistance in the bacterial population, 2) the use of cocktails containing antibiotic pairs, and 3) the imposition of tradeoff constraints on bacterial resistance to multiple drugs. Because of tradeoffs, bacterial resistance does not evolve directionally and the system reaches an equilibrium state. When considering the equilibrium frequency of uninfected patients, both cycling and mixing improve upon single-drug treatment strategies. Mixing outperforms optimal cycling regimens. Cocktails further improve upon aforementioned strategies. Moreover, conditions that increase the population frequency of uninfected patients also increase the recovery rate of infected individual patients. Thus, a rational strategy does not necessarily result in a tragedy of the commons because benefits to the individual patient and general public are not in conflict. Our identification of cocktails as the best strategy when tradeoffs between multiple-resistance are operating could also be extended to other host-pathogen systems. Cocktails or other multiple-drug treatments are additionally attractive because they allow re-using antibiotics whose utility has been negated by the evolution of single resistance.

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

PubMed

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

2015-09-01

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

What is epistemic value in free energy models of learning and acting? A bounded rationality perspective.

PubMed

Ortega, Pedro A; Braun, Daniel A

2015-01-01

Free energy models of learning and acting do not only care about utility or extrinsic value, but also about intrinsic value, that is, the information value stemming from probability distributions that represent beliefs or strategies. While these intrinsic values can be interpreted as epistemic values or exploration bonuses under certain conditions, the framework of bounded rationality offers a complementary interpretation in terms of information-processing costs that we discuss here.

A survey on the factors influencing the pattern of medicine's use: Concerns on irrational use of drugs.

PubMed

Soleymani, Fatemeh; Ahmadizar, Fariba; Meysamie, Alipasha; Abdollahi, Mohammad

2013-04-01

Pharmacists have a remarkable role in rational use of drugs by dissemination of drug information to guide patients, physicians, and policy makers. The present study was undertaken to evaluate the pharmacists' view point about the main factors affecting current drug use pattern regarding rational drug use and the most effective strategies for improving and promoting rational drug use among pharmacists. In a cross-sectional survey, pre-designed questionnaires were filled in convenient sampling by pharmacists who had attended the congress of rational drug use in Tehran, Iran. A total of 144 pharmacists with the average age of 40.78 years old were enrolled to the study. Data indicated that the most priorities in irrational use of drugs from pharmacists' view point were lack of appropriate cooperation and communication between physicians and pharmacists (39%), pharmacists' low tariff and economic issues (34%), lack of public knowledge about drug usage (45%), and lack of supervisory regulations on pharmacy practice (15.8%). In this study, lack of public knowledge and awareness about appropriate use of medicines was the most important element from pharmacists' viewpoint in occurrence of irrational drug use. Dissemination of information and compiling of diverse strategies in education, management, regulation, and finance can be very efficient due to a strong relationship between drug policies and performance of regulations and supervisions as well as drug services.

pH-Controlled Assembly of DNA Tiles

DOE PAGES

Amodio, Alessia; Adedeji, Abimbola Feyisara; Castronovo, Matteo; ...

2016-09-15

We demonstrate a strategy to trigger and finely control the assembly of supramolecular DNA nanostructures with pH. Control is achieved via a rationally designed strand displacement circuit that responds to pH and activates a downstream DNA tile self-assembly process. We observe that the DNA structures form under neutral/basic conditions, while the self-assembly process is suppressed under acidic conditions. The strategy presented here demonstrates a modular approach toward building systems capable of processing biochemical inputs and finely controlling the assembly of DNA-based nanostructures under isothermal conditions. In particular, the presented architecture is relevant for the development of complex DNA devices ablemore » to sense and respond to molecular markers associated with abnormal metabolism.« less

pH-Controlled Assembly of DNA Tiles

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

Amodio, Alessia; Adedeji, Abimbola Feyisara; Castronovo, Matteo

We demonstrate a strategy to trigger and finely control the assembly of supramolecular DNA nanostructures with pH. Control is achieved via a rationally designed strand displacement circuit that responds to pH and activates a downstream DNA tile self-assembly process. We observe that the DNA structures form under neutral/basic conditions, while the self-assembly process is suppressed under acidic conditions. The strategy presented here demonstrates a modular approach toward building systems capable of processing biochemical inputs and finely controlling the assembly of DNA-based nanostructures under isothermal conditions. In particular, the presented architecture is relevant for the development of complex DNA devices ablemore » to sense and respond to molecular markers associated with abnormal metabolism.« less

Systems, Shocks and Time Bombs

NASA Astrophysics Data System (ADS)

Winder, Nick

The following sections are included: * Introduction * Modelling strategies * Are time-bomb phenomena important? * Heuristic approaches to time-bomb phenomena * Three rational approaches to TBP * Two irrational approaches * Conclusions * References

A survey of Ethiopian physicians' experiences of bedside rationing: extensive resource scarcity, tough decisions and adverse consequences.

PubMed

Defaye, Frehiwot Berhane; Desalegn, Dawit; Danis, Marion; Hurst, Samia; Berhane, Yemane; Norheim, Ole Frithjof; Miljeteig, Ingrid

2015-10-14

Resource scarcity in health care is a universal challenge. In high-income settings, bedside rationing is commonly discussed and debated as a means to addressing scarcity. However, little is known about physicians' experiences in resource-limited contexts in low- income countries. Here we describe physicians' experiences regarding scarcity of resources, bedside rationing, use of various strategies to save resources, and perceptions of the consequences of rationing in Ethiopia. A national survey was conducted amongst physicians from 49 public hospitals using stratified, multi-stage sampling in six regions. All physicians in the selected hospitals were invited to respond to a self-administered questionnaire. Data were weighted and analyzed using descriptive statistics. In total, 587 physicians responded (91% response rate). The majority had experienced system-wide shortages of various types of medical services. The services most frequently reported to be in short supply, either daily or weekly, were access to surgery, specialist and intensive care units, drug prescriptions and admission to hospital (52, 49, 46, 47 and 46% respectively). The most common rationing strategies used daily or weekly were limiting laboratory tests, hospital drugs, radiological investigations and providing second best treatment (47, 47, 47 and 39% respectively). Availability of institutional or national guidelines for whom to see and treat first was lacking. Almost all respondents had witnessed different adverse consequences of resource scarcity; 54% reported seeing patients who, in their estimation, had died due to resource scarcity. Almost 9 out of 10 physicians were so troubled by limited resources that they often regretted their choice of profession. This study provides the first glimpses of the untold story of resource shortage and bedside rationing in Ethiopia. Physicians encounter numerous dilemmas due to resource scarcity, and they report they lack adequate guidance for how to handle them. The consequences for patients and the professionals are substantial.

Systematic development of small molecules to inhibit specific microscopic steps of Aβ42 aggregation in Alzheimer's disease.

PubMed

Habchi, Johnny; Chia, Sean; Limbocker, Ryan; Mannini, Benedetta; Ahn, Minkoo; Perni, Michele; Hansson, Oskar; Arosio, Paolo; Kumita, Janet R; Challa, Pavan Kumar; Cohen, Samuel I A; Linse, Sara; Dobson, Christopher M; Knowles, Tuomas P J; Vendruscolo, Michele

2017-01-10

The aggregation of the 42-residue form of the amyloid-β peptide (Aβ42) is a pivotal event in Alzheimer's disease (AD). The use of chemical kinetics has recently enabled highly accurate quantifications of the effects of small molecules on specific microscopic steps in Aβ42 aggregation. Here, we exploit this approach to develop a rational drug discovery strategy against Aβ42 aggregation that uses as a read-out the changes in the nucleation and elongation rate constants caused by candidate small molecules. We thus identify a pool of compounds that target specific microscopic steps in Aβ42 aggregation. We then test further these small molecules in human cerebrospinal fluid and in a Caenorhabditis elegans model of AD. Our results show that this strategy represents a powerful approach to identify systematically small molecule lead compounds, thus offering an appealing opportunity to reduce the attrition problem in drug discovery.

Future vaccination strategies against tuberculosis: thinking outside the box.

PubMed

Kaufmann, Stefan H E

2010-10-29

With almost a dozen vaccine candidates in clinical trials, tuberculosis (TB) research and development is finally reaping the first fruits of its labors. Vaccine candidates in clinical trials may prevent TB disease reactivation by efficiently containing the pathogen Mycobacterium tuberculosis (Mtb). Future research should target vaccines that achieve sterile eradication of Mtb or even prevent stable infection. These are ambitious goals that can be reached only by highly cooperative engagement of basic immunologists, vaccinologists, and clinical researchers--or in other words, by translation from basic immunology to vaccine research and development, as well as reverse translation of insights from clinical trials back to hypothesis-driven research in the basic laboratory. Here, we review current and future strategies toward the rational design of novel vaccines against TB, as well as the progress made thus far, and the hurdles that need to be overcome in the near and distant future. Copyright © 2010 Elsevier Inc. All rights reserved.

Authority Base, Denomination, Moral Philosophy and the Power Strategies Used by Clergymen.

ERIC Educational Resources Information Center

Falbo, Toni; And Others

Clergymen are regarded by their congregations as having the authority to influence church members and clergymen are expected to exert influence. Three types of clerical authority have been identified: charismatic, traditional, and legal-rational. The common assumption that people select power strategies that are consistent with their perceptions…

[Nudge strategies at a glance: an overview. More freedom or new paternalism?

PubMed

Leone, Luca

2016-01-01

Under the theoretical assumptions of individual bounded rationality and of behavioural psychology about human actions and agency, nudge has been promoted as an alternative to traditional regulatory tools, characterized by being inexpensive, choice-preserving, and bound to promote legitimate goals and citizens' welfare within through specific choice architectures. Applicable to several domains, health included, the nudging approach runs in connection with requests and needs arising from marketing strategies, with the aim of maximizing economic rationality and efficiency. However, as nudge was framed having in mind the notion of consumer, it fails to fully meet the values connected to the idea of citizenship. Most nudges strategies seem to imply a top-down vision - though soft paternalistic - where pre-defined and often black-boxed values pretend to define individual and collective directions. The representational and ethical issues surrounding nudge, the psychological mechanisms working behind it, and the correlated legal issues request a precise and accurate scrutiny, if we want nudging interventions to be legitimately and democratically framed within policy strategies and human agency not to be disregarded, but empowered by behaviourally-based actions.

What Information Theory Says About Best Response and About Binding Contracts

NASA Technical Reports Server (NTRS)

Wolpert, David H.

2004-01-01

Product Distribution (PD) theory is the information-theoretic extension of conventional full- rationality game theory to bounded rational games. Here PD theory is used to investigate games in which the players use bounded rational best-response strategies. This investigation illuminates how to determine the optimal organization chart for a corporation, or more generally how to order the sequence of moves of the players / employees so as to optimize an overall objective function. It is then shown that in the continuum-time limit, bounded rational best response games result in a variant of the replicator dynamics of evolutionary game theory. This variant is then investigated for team games, in which the players share the same utility function, by showing that such continuum- limit bounded rational best response is identical to Newton-Raphson iterative optimization of the shared utility function. Next PD theory is used to investigate changing the coordinate system of the game, i.e., changing the mapping from the joint move of the players to the arguments in the utility functions. Such a change couples those arguments, essentially by making each players move be an offered binding contract.

Hunters' acceptability of the surveillance system and alternative surveillance strategies for classical swine fever in wild boar - a participatory approach.

PubMed

Schulz, Katja; Calba, Clémentine; Peyre, Marisa; Staubach, Christoph; Conraths, Franz J

2016-09-06

Surveillance measures can only be effective if key players in the system accept them. Acceptability, which describes the willingness of persons to contribute, is often analyzed using participatory methods. Participatory epidemiology enables the active involvement of key players in the assessment of epidemiological issues. In the present study, we used a participatory method recently developed by CIRAD (Centre de Coopération Internationale en Recherche Agronomique pour le Développement) to evaluate the functionality and acceptability of Classical Swine Fever (CSF) surveillance in wild boar in Germany, which is highly dependent on the participation of hunters. The acceptability of alternative surveillance strategies was also analyzed. By conducting focus group discussions, potential vulnerabilities in the system were detected and feasible alternative surveillance strategies identified. Trust in the current surveillance system is high, whereas the acceptability of the operation of the system is medium. Analysis of the acceptability of alternative surveillance strategies showed how risk-based surveillance approaches can be combined to develop strategies that have sufficient support and functionality. Furthermore, some surveillance strategies were clearly rejected by the hunters. Thus, the implementation of such strategies may be difficult. Participatory methods can be used to evaluate the functionality and acceptability of existing surveillance plans for CSF among hunters and to optimize plans regarding their chances of successful implementation.

The Next Breakthrough for Organic Photovoltaics?

PubMed

Jackson, Nicholas E; Savoie, Brett M; Marks, Tobin J; Chen, Lin X; Ratner, Mark A

2015-01-02

While the intense focus on energy level tuning in organic photovoltaic materials has afforded large gains in device performance, we argue here that strategies based on microstructural/morphological control are at least as promising in any rational design strategy. In this work, a meta-analysis of ∼150 bulk heterojunction devices fabricated with different materials combinations is performed and reveals strong correlations between power conversion efficiency and morphology-dominated properties (short-circuit current, fill factor) and surprisingly weak correlations between efficiency and energy level positioning (open-circuit voltage, enthalpic offset at the interface, optical gap). While energy level positioning should in principle provide the theoretical maximum efficiency, the optimization landscape that must be navigated to reach this maximum is unforgiving. Thus, research aimed at developing understanding-based strategies for more efficient optimization of an active layer microstructure and morphology are likely to be at least as fruitful.

A strategy for space biology and medical science for the 1980s and 1990s

NASA Technical Reports Server (NTRS)

1987-01-01

A guideline is provided for developing NASA's long-term mission plans and a rational, coherent research program. Ten topical areas for research are addressed: developmental biology, gravitropism in plants, sensorimotor integration, bone and mineral metabolism, cardiovascular/pulmonary function, muscle remodeling, nutrition, human reproduction, space anemia, and human behavior. Scientific goals, objectives, and required measurements and facilities for each of the major areas of space biology and medicine are identified and described along with primary goals and objectives for each of these disciplines. Proposals are made concerning the use of scientific panels to oversee the implementation of the strategy, life sciences' need for continuous access to spaceflight opportunities, the advantages of a focused mission strategy, certain design features that will enhance spaceflight experimentation, and general facilities. Other topics that are considered include mission planning, crew selection and training, and interagency and international cooperation.

Unbending mind: Individuals with hoarding disorder do not modify decision strategy in response to feedback under risk.

PubMed

Pushkarskaya, Helen; Tolin, David F; Henick, Daniel; Levy, Ifat; Pittenger, Christopher

2018-01-01

Cognitive-behavioral models of hoarding disorder emphasize impairments in information processing and decision making in the genesis of hoarding symptomology. We propose and test the novel hypothesis that individuals with hoarding are maladaptively biased towards a deliberative decision style. While deliberative strategies are often considered normative, they are not always adaptable to the limitations imposed by many real-world decision contexts. We examined decision-making patterns in 19 individuals with hoarding and 19 healthy controls, using a behavioral task that quantifies selection of decision strategies in a novel environment with known probabilities (risk) in response to feedback. Consistent with prior literature, we found that healthy individuals tend to explore different decision strategies in the beginning of the experiment, but later, in response to feedback, they shift towards a compound strategy that balances expected values and risks. In contrast, individuals with hoarding follow a simple, deliberative, risk-neutral, value-based strategy from the beginning to the end of the task, irrespective of the feedback. This seemingly rational approach was not ecologically rational: individuals with hoarding and healthy individuals earned about the same amount of money, but it took individuals with hoarding a lot longer to do it: additional cognitive costs did not lead to additional benefits. Copyright © 2017 Elsevier B.V. All rights reserved.

New strategy for drug discovery by large-scale association analysis of molecular networks of different species.

PubMed

Zhang, Bo; Fu, Yingxue; Huang, Chao; Zheng, Chunli; Wu, Ziyin; Zhang, Wenjuan; Yang, Xiaoyan; Gong, Fukai; Li, Yuerong; Chen, Xiaoyu; Gao, Shuo; Chen, Xuetong; Li, Yan; Lu, Aiping; Wang, Yonghua

2016-02-25

The development of modern omics technology has not significantly improved the efficiency of drug development. Rather precise and targeted drug discovery remains unsolved. Here a large-scale cross-species molecular network association (CSMNA) approach for targeted drug screening from natural sources is presented. The algorithm integrates molecular network omics data from humans and 267 plants and microbes, establishing the biological relationships between them and extracting evolutionarily convergent chemicals. This technique allows the researcher to assess targeted drugs for specific human diseases based on specific plant or microbe pathways. In a perspective validation, connections between the plant Halliwell-Asada (HA) cycle and the human Nrf2-ARE pathway were verified and the manner by which the HA cycle molecules act on the human Nrf2-ARE pathway as antioxidants was determined. This shows the potential applicability of this approach in drug discovery. The current method integrates disparate evolutionary species into chemico-biologically coherent circuits, suggesting a new cross-species omics analysis strategy for rational drug development.

Predictive modeling studies for the ecotoxicity of ionic liquids towards the green algae Scenedesmus vacuolatus.

PubMed

Das, Rudra Narayan; Roy, Kunal

2014-06-01

Hazardous potential of ionic liquids is becoming an issue of high concern with increasing application of these compounds in various industrial processes. Predictive toxicological modeling on ionic liquids provides a rational assessment strategy and aids in developing suitable guidance for designing novel analogues. The present study attempts to explore the chemical features of ionic liquids responsible for their ecotoxicity towards the green algae Scenedesmus vacuolatus by developing mathematical models using extended topochemical atom (ETA) indices along with other categories of chemical descriptors. The entire study has been conducted with reference to the OECD guidelines for QSAR model development using predictive classification and regression modeling strategies. The best models from both the analyses showed that ecotoxicity of ionic liquids can be decreased by reducing chain length of cationic substituents and increasing hydrogen bond donor feature in cations, and replacing bulky unsaturated anions with simple saturated moiety having less lipophilic heteroatoms. Copyright © 2013 Elsevier Ltd. All rights reserved.

Molecular mechanisms of action of bacterial exotoxins.

PubMed

Balfanz, J; Rautenberg, P; Ullmann, U

1996-07-01

Toxins are one of the inventive strategies that bacteria have developed in order to survive. As virulence factors, they play a major role in the pathogenesis of infectious diseases. Recent discoveries have once more highlighted the effectiveness of these precisely adjusted bacterial weapons. Furthermore, toxins have become an invaluable tool in the investigation of fundamental cell processes, including regulation of cellular functions by various G proteins, cytoskeletal dynamics and neural transmission. In this review, the bacterial toxins are presented in a rational classification based on the molecular mechanisms of action.

Directed molecular evolution to design advanced red fluorescent proteins.

PubMed

Subach, Fedor V; Piatkevich, Kiryl D; Verkhusha, Vladislav V

2011-11-29

Fluorescent proteins have become indispensable imaging tools for biomedical research. Continuing progress in fluorescence imaging, however, requires probes with additional colors and properties optimized for emerging techniques. Here we summarize strategies for development of red-shifted fluorescent proteins. We discuss possibilities for knowledge-based rational design based on the photochemistry of fluorescent proteins and the position of the chromophore in protein structure. We consider advances in library design by mutagenesis, protein expression systems and instrumentation for high-throughput screening that should yield improved fluorescent proteins for advanced imaging applications.

CONTRIBUTIONS TO RATIONAL APPROXIMATION,

DTIC Science & Technology

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)

Review of control strategies for robotic movement training after neurologic injury.

PubMed

Marchal-Crespo, Laura; Reinkensmeyer, David J

2009-06-16

There is increasing interest in using robotic devices to assist in movement training following neurologic injuries such as stroke and spinal cord injury. This paper reviews control strategies for robotic therapy devices. Several categories of strategies have been proposed, including, assistive, challenge-based, haptic simulation, and coaching. The greatest amount of work has been done on developing assistive strategies, and thus the majority of this review summarizes techniques for implementing assistive strategies, including impedance-, counterbalance-, and EMG- based controllers, as well as adaptive controllers that modify control parameters based on ongoing participant performance. Clinical evidence regarding the relative effectiveness of different types of robotic therapy controllers is limited, but there is initial evidence that some control strategies are more effective than others. It is also now apparent there may be mechanisms by which some robotic control approaches might actually decrease the recovery possible with comparable, non-robotic forms of training. In future research, there is a need for head-to-head comparison of control algorithms in randomized, controlled clinical trials, and for improved models of human motor recovery to provide a more rational framework for designing robotic therapy control strategies.

Review of control strategies for robotic movement training after neurologic injury

PubMed Central

Marchal-Crespo, Laura; Reinkensmeyer, David J

2009-01-01

There is increasing interest in using robotic devices to assist in movement training following neurologic injuries such as stroke and spinal cord injury. This paper reviews control strategies for robotic therapy devices. Several categories of strategies have been proposed, including, assistive, challenge-based, haptic simulation, and coaching. The greatest amount of work has been done on developing assistive strategies, and thus the majority of this review summarizes techniques for implementing assistive strategies, including impedance-, counterbalance-, and EMG- based controllers, as well as adaptive controllers that modify control parameters based on ongoing participant performance. Clinical evidence regarding the relative effectiveness of different types of robotic therapy controllers is limited, but there is initial evidence that some control strategies are more effective than others. It is also now apparent there may be mechanisms by which some robotic control approaches might actually decrease the recovery possible with comparable, non-robotic forms of training. In future research, there is a need for head-to-head comparison of control algorithms in randomized, controlled clinical trials, and for improved models of human motor recovery to provide a more rational framework for designing robotic therapy control strategies. PMID:19531254

Self-reported strategies in decisions under risk: role of feedback, reasoning abilities, executive functions, short-term-memory, and working memory.

PubMed

Schiebener, Johannes; Brand, Matthias

2015-11-01

In decisions under objective risk conditions information about the decision options' possible outcomes and the rules for outcomes' occurrence are provided. Thus, deciders can base decision-making strategies on probabilistic laws. In many laboratory decision-making tasks, choosing the option with the highest winning probability in all trials (=maximization strategy) is probabilistically regarded the most rational behavior. However, individuals often behave less optimal, especially in case the individuals have lower cognitive functions or in case no feedback about consequences is provided in the situation. It is still unclear which cognitive functions particularly predispose individuals for using successful strategies and which strategies profit from feedback. We investigated 195 individuals with two decision-making paradigms, the Game of Dice Task (GDT) (with and without feedback), and the Card Guessing Game. Thereafter, participants reported which strategies they had applied. Interaction effects (feedback × strategy), effect sizes, and uncorrected single group comparisons suggest that feedback in the GDT tended to be more beneficial to individuals reporting exploratory strategies (e.g., use intuition). In both tasks, the self-reported use of more principled and more rational strategies was accompanied by better decision-making performance and better performances in reasoning and executive functioning tasks. The strategy groups did not significantly differ in most short-term and working-memory tasks. Thus, particularly individual differences in reasoning and executive functions seem to predispose individuals toward particular decision-making strategies. Feedback seems to be useful for individuals who rather explore the decision-making situation instead of following a certain plan.

Book Selection, Collection Development, and Bounded Rationality.

ERIC Educational Resources Information Center

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)…

Rational Behavior Skills: A Teaching Sequence for Students with Emotional Disabilities.

ERIC Educational Resources Information Center

Patton, Patricia Lucey

1995-01-01

Rational behavior training is a proactive teaching model concerned with helping students with behavior disorders or serious emotional disturbances develop rational thinking and appropriate social skills. Describes a seven-session sequence for teaching rational behavior skills in a middle school setting. Pre- and posttest data revealed significant…

Bridging or Buffering? The Impact of Schools' Adaptive Strategies on Student Achievement

ERIC Educational Resources Information Center

DiPaola, Michael F.; Tschannen-Moran, Megan

2005-01-01

Purpose: Rational and open system theories offer divergent sets of tactics on how best to deal with factors outside the boundary of the school. This study compared two competing strategies that emerge from these theories: bridging and buffering. The impact of how schools interact with their environments was examined in relation to student…

Rational development of two flowthrough purification strategies for adenovirus type 5 and retro virus-like particles.

PubMed

Nestola, Piergiuseppe; Peixoto, Cristina; Villain, Louis; Alves, Paula M; Carrondo, Manuel J T; Mota, José P B

2015-12-24

We report on the rational design and implementation of flowthrough (FT) platforms for purification of virus vectors (VVs) and virus-like particles (VLPs), combining anion-exchange polyallylamine membranes (Sartobind STIC) and core-shell octylamine resins (CaptoCore 700). In one configuration, the VV bulk is concentrated and conditioned with appropriate buffer in a ultra/diafiltration (UF/DF) unit prior to injection into the STIC chromatography membrane. The FT pool and an intermediate cut of the elution pool of the STIC membrane are admixed and directed to a second UF/DF. Finally, the retentate is injected into a CC700 packed bed adsorber where the purified VVs are collected in the FT pool, whereas the residual amount of DNA and host cell protein (HCP) are discarded in the eluate. The experimental recovery achieved with this downstream processing (DSP) platform is close to 100%, the DNA clearance is roughly a 4-log reduction, and the HCP level is reduced by 5 logs. The platform developed for VLP purification is simpler than the previous one, as the STIC membrane adsorber and CC700 bed are connected in series with no UF/DF unit in between. Experimentally, the FT scheme for VLP purification gave a recovery yield of 45% in the chromatography train; the experimental log reduction of DNA and HCP were 2.0 and 3.5, respectively. These results are in line with other purification strategies in the specific field of enveloped VLPs. Both DSP platforms were successfully developed from an initial design space of the binding of the major contaminant (DNA) to the two ligands, determined by surface plasmon resonance, which was subsequently scaled up and confirmed experimentally. Copyright © 2015 Elsevier B.V. All rights reserved.

Skp1: Implications in cancer and SCF-oriented anti-cancer drug discovery.

PubMed

Hussain, Muzammal; Lu, Yongzhi; Liu, Yong-Qiang; Su, Kai; Zhang, Jiancun; Liu, Jinsong; Zhou, Guang-Biao

2016-09-01

In the last decade, the ubiquitin proteasome system (UPS), in general, and E3 ubiquitin ligases, in particular, have emerged as valid drug targets for the development of novel anti-cancer therapeutics. Cullin RING Ligases (CRLs), which can be classified into eight groups (CRL1-8) and comprise approximately 200 members, represent the largest family of E3 ubiquitin ligases which facilitate the ubiquitination-derived proteasomal degradation of a myriad of functionally and structurally diverse substrates. S phase kinase-associated protein 1 (Skp1)-Cullin1-F-Box protein (SCF) complexes are the best characterized among CRLs, which play crucial roles in numerous cellular processes and physiological dysfunctions, such as in cancer biology. Currently, there is growing interest in developing SCF-targeting anti-cancer therapies for clinical application. Indeed, the research in this field has seen some progress in the form of cullin neddylation- and Skp2-inhibitors. However, it still remains an underdeveloped area and needs to design new strategies for developing improved form of therapy. In this review, we venture a novel strategy that rational pharmacological targeting of Skp1, a central regulator of SCF complexes, may provide a novel avenue for SCF-oriented anti-cancer therapy, expected: (i) to simultaneously address the critical roles that multiple SCF oncogenic complexes play in cancer biology, (ii) to selectively target cancer cells with minimal normal cell toxicity, and (iii) to offer multiple chemical series, via therapeutic interventions at the Skp1 binding interfaces in SCF complex, thereby maximizing chances of success for drug discovery. In addition, we also discuss the challenges that might be posed regarding rational pharmacological interventions against Skp1. Copyright © 2016 Elsevier Ltd. All rights reserved.

Voices of the poor from the margins of Bengal: structural inequities and health.

PubMed

Dutta, Mohan J; Dutta, Uttaran

2013-01-01

In opposition to the traditional approaches to health communication that treat the subaltern sectors as passive recipients of messages of enlightenment configured in top-down interventions, the culture-centered approach foregrounds the importance of listening to subaltern communities at the margins through dialogue. We build on earlier culture-centered projects in rural communities of West Bengal, India, to develop participatory research strategies for understanding the local processes through which the structural marginalization of the poor plays out in rural Bengal. Study results point toward the marginalization of the poor both communicatively and economically, attending to the ways in which communicative marginalization lies at the heart of economic oppressions. Through locally articulated concepts of "health as shortage" and "communication as shortage," community members put forth alternative rationalities of health that highlight structural resources at the heart of health. These local articulations of shortage offer an alternative rationality for organizing health promotion efforts in the rural margins of Bengal through the foregrounding of discourses of shortage.

Prostatitis: myths and realities.

PubMed

Nickel, J C

1998-03-01

To explore the myths surrounding the enigmatic syndrome that the urologic community has labeled as prostatitis and to determine the actual realities associated with this disease. A critical evaluation of the syndrome of prostatitis based on examination of the recent world literature, undisputed scientific facts, solid hypotheses, common sense, and the author's personal opinion. The most common myths surrounding the importance, etiology, diagnosis, classification, and treatment of prostatitis are in fact merely myths. Recent research has led to a new awareness of the importance of prostatitis, new insights into its pathogenesis, improved disease classification and symptom assessment, and will ultimately lead to more rational diagnostic and treatment strategies. The introduction of a new more rational classification system, the development and validation of reliable symptom assessment instruments, new funding initiatives by granting agencies and the pharmaceutical industry, and an awakening appeal for intellectual examination of this common prostate disease by academic urologists guarantees that prostatitis will find an important place on the urologic agenda as we enter the next millennium.

Improvement of Biocatalysts for Industrial and Environmental Purposes by Saturation Mutagenesis

PubMed Central

Valetti, Francesca; Gilardi, Gianfranco

2013-01-01

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

3D printing of optical materials: an investigation of the microscopic properties

NASA Astrophysics Data System (ADS)

Persano, Luana; Cardarelli, Francesco; Arinstein, Arkadii; Uttiya, Sureeporn; Zussman, Eyal; Pisignano, Dario; Camposeo, Andrea

2018-02-01

3D printing technologies are currently enabling the fabrication of objects with complex architectures and tailored properties. In such framework, the production of 3D optical structures, which are typically based on optical transparent matrices, optionally doped with active molecular compounds and nanoparticles, is still limited by the poor uniformity of the printed structures. Both bulk inhomogeneities and surface roughness of the printed structures can negatively affect the propagation of light in 3D printed optical components. Here we investigate photopolymerization-based printing processes by laser confocal microscopy. The experimental method we developed allows the printing process to be investigated in-situ, with microscale spatial resolution, and in real-time. The modelling of the photo-polymerization kinetics allows the different polymerization regimes to be investigated and the influence of process variables to be rationalized. In addition, the origin of the factors limiting light propagation in printed materials are rationalized, with the aim of envisaging effective experimental strategies to improve optical properties of printed materials.

Rationally Designed Hierarchically Structured Tungsten Nitride and Nitrogen-Rich Graphene-Like Carbon Nanocomposite as Efficient Hydrogen Evolution Electrocatalyst.

PubMed

Zhu, Yanping; Chen, Gao; Zhong, Yijun; Zhou, Wei; Shao, Zongping

2018-02-01

Practical application of hydrogen production from water splitting relies strongly on the development of low-cost and high-performance electrocatalysts for hydrogen evolution reaction (HER). The previous researches mainly focused on transition metal nitrides as HER catalysts due to their electrical conductivity and corrosion stability under acidic electrolyte, while tungsten nitrides have reported poorer activity for HER. Here the activity of tungsten nitride is optimized through rational design of a tungsten nitride-carbon composite. More specifically, tungsten nitride (WN x ) coupled with nitrogen-rich porous graphene-like carbon is prepared through a low-cost ion-exchange/molten-salt strategy. Benefiting from the nanostructured WN x , the highly porous structure and rich nitrogen dopant (9.5 at%) of the carbon phase with high percentage of pyridinic-N (54.3%), and more importantly, their synergistic effect, the composite catalyst displays remarkably high catalytic activity while maintaining good stability. This work highlights a powerful way to design more efficient metal-carbon composites catalysts for HER.

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

PubMed

Arganda-Carreras, Ignacio; Andrey, Philippe

2017-01-01

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

A polyalanine peptide derived from polar fish with anti-infectious activities

NASA Astrophysics Data System (ADS)

Cardoso, Marlon H.; Ribeiro, Suzana M.; Nolasco, Diego O.; de La Fuente-Núñez, César; Felício, Mário R.; Gonçalves, Sónia; Matos, Carolina O.; Liao, Luciano M.; Santos, Nuno C.; Hancock, Robert E. W.; Franco, Octávio L.; Migliolo, Ludovico

2016-02-01

Due to the growing concern about antibiotic-resistant microbial infections, increasing support has been given to new drug discovery programs. A promising alternative to counter bacterial infections includes the antimicrobial peptides (AMPs), which have emerged as model molecules for rational design strategies. Here we focused on the study of Pa-MAP 1.9, a rationally designed AMP derived from the polar fish Pleuronectes americanus. Pa-MAP 1.9 was active against Gram-negative planktonic bacteria and biofilms, without being cytotoxic to mammalian cells. By using AFM, leakage assays, CD spectroscopy and in silico tools, we found that Pa-MAP 1.9 may be acting both on intracellular targets and on the bacterial surface, also being more efficient at interacting with anionic LUVs mimicking Gram-negative bacterial surface, where this peptide adopts α-helical conformations, than cholesterol-enriched LUVs mimicking mammalian cells. Thus, as bacteria present varied physiological features that favor antibiotic-resistance, Pa-MAP 1.9 could be a promising candidate in the development of tools against infections caused by pathogenic bacteria.

The Nurse Project: an analysis for nurses to take back our work.

PubMed

Rankin, Janet M

2009-12-01

This paper challenges nurses to join together as a collective in order to facilitate ongoing analysis of the issues that arise for nurses and patients when nursing care is harnessed for health care efficiencies. It is a call for nurses to respond with a collective strategy through which we can 'talk back' and 'act back' to the powerful rationality of current thinking and practices. The paper uses examples from an institutional ethnographic (IE) research project to demonstrate how dominant approaches to understanding nursing position nurses to overlook how we activate practices of reform that reorganize how we nurse. The paper then describes two classroom strategies taken from my work with students in undergraduate and graduate programs. The teaching strategies I describe rely on the theoretical framework that underpin the development of an IE analysis. Taken into the classroom (or into other venues of nursing activism) the tools of IE can be adapted to inform a pedagogical approach that supports nurses to develop an alternate analysis to what is happening in our work.

Technological Innovations from NASA

NASA Technical Reports Server (NTRS)

Pellis, Neal R.

2006-01-01

The challenge of human space exploration places demands on technology that push concepts and development to the leading edge. In biotechnology and biomedical equipment development, NASA science has been the seed for numerous innovations, many of which are in the commercial arena. The biotechnology effort has led to rational drug design, analytical equipment, and cell culture and tissue engineering strategies. Biomedical research and development has resulted in medical devices that enable diagnosis and treatment advances. NASA Biomedical developments are exemplified in the new laser light scattering analysis for cataracts, the axial flow left ventricular-assist device, non contact electrocardiography, and the guidance system for LASIK surgery. Many more developments are in progress. NASA will continue to advance technologies, incorporating new approaches from basic and applied research, nanotechnology, computational modeling, and database analyses.

Fiber sources for complete calf starter rations.

PubMed

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.

Performance of small-scale dairy farms in the highlands of central Mexico during the dry season under traditional feeding strategies.

PubMed

Martínez-García, Carlos Galdino; Rayas-Amor, Adolfo Armando; Anaya-Ortega, Juan Pablo; Martínez-Castañeda, Francisco Ernesto; Espinoza-Ortega, Angélica; Prospero-Bernal, Fernando; Arriaga-Jordán, Carlos Manuel

2015-02-01

In Mexico, small-scale dairy systems (SSDS) represent over 78 % of dairy farms and contribute with 37 % of national milk production; however, they face high feeding costs. The objective of this study was to assess the performance of SSDS during the dry season in terms of milk yields, milk composition and feeding costs under traditional feeding strategies, to identify areas of opportunity for improving their profitability. The information was collected from 22 SSDS every month during dry season. Feeds were classified in quality forages (QF), supplements (SU) and straws (ST). Two factors were identified: factor 1-a positive relationship among QF, SU, milk yield and ration cost and factor 2-represented straw usage. Four feeding strategies were identified: (1) low-cost feeding strategy; (2) home-grown feeding strategy; (3) high-cost feeding strategy; and (4) straw-based feeding strategy. There were differences (P < 0.001) among feeding strategies for QF, SU, ST, total dry matter offered (TDMO), ration cost (RC), external inputs, home-grown inputs and milk yield. There were no significant (P > 0.05) differences among feeding strategies for fat and protein contents in milk. It is concluded that to improve performance and profitability and enhance sustainability in SSDS, farmers should base feeding strategies on home-grown quality forages, as it was the case in group 2 which showed lower feeding cost and better milk yield. It is also recommended to increase the inclusion of quality forages like grazing pastures and maize silages during the dry season and to avoid the inclusion of straws.

A MDMP for All Seasons: Modifying the MDMP for Success

DTIC Science & Technology

2004-05-26

4 Rational Decision - Making Theory ............................................................................. 5 Limited Rationality ... making instead of using the MDMP, which is an analytical decision - making process. Limited rationality and analytical decision - making will be discussed...limited rationality decision - making theories. FM 5.0 defines fundamentals of planning, such as commander’s involvement and developing creative plans

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

NASA Astrophysics Data System (ADS)

Fan, Yuhang; Cao, Gongze; He, Shibo; Chen, Jiming; Sun, Youxian

2016-12-01

Many real-world systems are composed of interdependent networks that rely on one another. Such networks are typically designed and operated by different entities, who aim at maximizing their own payoffs. There exists a game among these entities when designing their own networks. In this paper, we study the game investigating how the rational behaviors of entities impact the system robustness. We first introduce a mathematical model to quantify the interacting payoffs among varying entities. Then we study the Nash equilibrium of the game and compare it with the optimal social welfare. We reveal that the cooperation among different entities can be reached to maximize the social welfare in continuous game only when the average degree of each network is constant. Therefore, the huge gap between Nash equilibrium and optimal social welfare generally exists. The rationality of entities makes the system inherently deficient and even renders it extremely vulnerable in some cases. We analyze our model for two concrete systems with continuous strategy space and discrete strategy space, respectively. Furthermore, we uncover some factors (such as weakening coupled strength of interdependent networks, designing a suitable topology dependence of the system) that help reduce the gap and the system vulnerability.

A new rational-based optimal design strategy of ship structure based on multi-level analysis and super-element modeling method

NASA Astrophysics Data System (ADS)

Sun, Li; Wang, Deyu

2011-09-01

A new multi-level analysis method of introducing the super-element modeling method, derived from the multi-level analysis method first proposed by O. F. Hughes, has been proposed in this paper to solve the problem of high time cost in adopting a rational-based optimal design method for ship structural design. Furthermore, the method was verified by its effective application in optimization of the mid-ship section of a container ship. A full 3-D FEM model of a ship, suffering static and quasi-static loads, was used as the analyzing object for evaluating the structural performance of the mid-ship module, including static strength and buckling performance. Research results reveal that this new method could substantially reduce the computational cost of the rational-based optimization problem without decreasing its accuracy, which increases the feasibility and economic efficiency of using a rational-based optimal design method in ship structural design.

CoM(M=Fe,Cu,Ni)-embedded nitrogen-enriched porous carbon framework for efficient oxygen and hydrogen evolution reactions

NASA Astrophysics Data System (ADS)

Feng, Xiaogeng; Bo, Xiangjie; Guo, Liping

2018-06-01

Rational synthesis and development of earth-abundant materials with efficient electrocatalytic activity and stability for water splitting is a critical but challenging step for sustainable energy application. Herein, a family of bimetal (CoFe, CoCu, CoNi) embedded nitrogen-doped carbon frameworks is developed through a facile and simple thermal conversion strategy of metal-doped zeolitic imidazolate frameworks. Thanks to collaborative superiorities of abundant M-N-C species, modulation action of secondary metal, cobalt-based electroactive phases, template effect of MOFs and unique porous structure, bimetal embedded nitrogen-doped carbon frameworks materials manifest good oxygen and hydrogen evolution catalytic activity. Especially, after modulating the species and molar ratio of metal sources, optimal Co0.75Fe0.25 nitrogen-doped carbon framework catalyst just requires a low overpotential of 303 mV to achieve 10 mA cm-2 with a low Tafel slope (39.49 mV dec-1) for oxygen evolution reaction, which even surpasses that of commercial RuO2. In addition, the optimal catalyst can function as an efficient bifunctional electrocatalyst for overall water splitting with satisfying activity and stability. This development offers an attractive direction for the rational design and fabrication of porous carbon materials for electrochemical energy applications.

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

PubMed

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.

Effects of ionic strength and sugars on the aggregation propensity of monoclonal antibodies: influence of colloidal and conformational stabilities.

PubMed

Saito, Shuntaro; Hasegawa, Jun; Kobayashi, Naoki; Tomitsuka, Toshiaki; Uchiyama, Susumu; Fukui, Kiichi

2013-05-01

To develop a general strategy for optimizing monoclonal antibody (MAb) formulations. Colloidal stabilities of four representative MAbs solutions were assessed based on the second virial coefficient (B 2) at 20°C and 40°C, and net charges at different NaCl concentrations, and/or in the presence of sugars. Conformational stabilities were evaluated from the unfolding temperatures. The aggregation propensities were determined at 40°C and after freeze-thawing. The electrostatic potential of antibody surfaces was simulated for the development of rational formulations. Similar B 2 values were obtained at 20°C and 40°C, implying little dependence on temperature. B 2 correlated quantitatively with aggregation propensities at 40°C. The net charge partly correlated with colloidal stability. Salts stabilized or destabilized MAbs, depending on repulsive or attractive interactions. Sugars improved the aggregation propensity under freeze-thaw stress through improved conformational stability. Uneven and even distributions of potential surfaces were attributed to attractive and strong repulsive electrostatic interactions. Assessment of colloidal stability at the lowest ionic strength is particularly effective for the development of formulations. If necessary, salts are added to enhance the colloidal stability. Sugars further improved aggregation propensities by enhancing conformational stability. These behaviors are rationally predictable according to the surface potentials of MAbs.

Operation Borderstar Field Evaluation of the Ration, Lightweight, 30-Day

DTIC Science & Technology

1985-05-01

Lightweight, 30-Day (RLW-30) was conducted at Ft. Bliss, TX as part of work unit # AH99BF034 "Sensory and Behavioral Engineering of Low-Volume Rations...corresponding hedonic ratings obtained from the final questionnaire. B. Amounts of Ration Comsumed Daily self-reports of the amounts of each ration...Lightweight, 30-Day Food Packet Assault 23 LIGHT WEIGHT RATION QUESTIONNAIRE Behavioral Sciences Division U.S. Army Natick Research & Development Center

Rational Design of Porous Conjugated Polymers and Roles of Residual Palladium for Photocatalytic Hydrogen Production

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

Li, Lianwei; Cai, Zhengxu; Wu, Qinghe

Developing high efficient photocatalyts for splitting water into oxygen and hydrogen is one of the biggest chemical challenges in solar energy utilization. In this paper, we report our effort in rationally designing conjugated porous polymer (CPP) photocatalysts for photocatalytic hydrogen production (PHP) from water. A series of CPP photocatalysts with different chromophore components and bipyridyl (bpy) contents were synthesized and found to evolve hydrogen photocatalytically from water. The PHP activity of bpy-containing CPPs can be greatly enhanced due to the improved light absorption, better wettability, higher crystallinity and the improved charge separation process. Moreover, the CPP photocatalyst made of strongmore » and fully conjugated donor chromo-phore DBD shows the highest hydrogen production rate ~ 33 μmol/h. The results indicate that copolymerization between a strong donor and weak acceptor is a useful strategy for the devel-opment of efficient photocatalysts. This study clarifies that the residual palladium in the CPP networks plays a key role for the catalytic performance. The PHP activity of CPP photocatalyst can be further enhanced to 164 μmol/h with an apparent quantum yield of 1.8% at 350 nm by loading 2 wt% of extra platinum cocat-alyst.« less

Prediction of moment-rotation characteristic of top- and seat-angle bolted connection incorporating prying action

NASA Astrophysics Data System (ADS)

Ahmed, Ali

2017-03-01

Finite element (FE) analyses were performed to explore the prying influence on moment-rotation behaviour and to locate yielding zones of top- and seat-angle connections in author's past research studies. The results of those FE analyses with experimental failure strategies of the connections were used to develop failure mechanisms of top- and seat-angle connections in the present study. Then a formulation was developed based on three simple failure mechanisms considering bending and shear deformations, effects of prying action on the top angle and stiffness of the tension bolts to estimate rationally the ultimate moment M u of the connection, which is a vital parameter of the proposed four-parameter power model. Applicability of the proposed formulation is assessed by comparing moment-rotation ( M- θ r ) curves and ultimate moment capacities with those measured by experiments and estimated by FE analyses and three-parameter power model. This study shows that proposed formulation and Kishi-Chen's method both achieved close approximation driving M- θ r curves of all given connections except a few cases of Kishi-Chen model, and M u estimated by the proposed formulation is more rational than that predicted by Kishi-Chen's method.

Evaluating Determinants of Environmental Risk Perception for Risk Management in Contaminated Sites

PubMed Central

Janmaimool, Piyapong; Watanabe, Tsunemi

2014-01-01

Understanding the differences in the risk judgments of residents of industrial communities potentially provides insights into how to develop appropriate risk communication strategies. This study aimed to explore citizens’ fundamental understanding of risk-related judgments and to identify the factors contributing to perceived risks. An exploratory model was created to investigate the public’s risk judgments. In this model, the relationship between laypeople’s perceived risks and the factors related to the physical nature of risks (such as perceived probability of environmental contamination, probability of receiving impacts, and severity of catastrophic consequences) were examined by means of multiple regression analysis. Psychological factors, such as the ability to control the risks, concerns, experiences, and perceived benefits of industrial development were also included in the analysis. The Maptaphut industrial area in Rayong Province, Thailand was selected as a case study. A survey of 181 residents of communities experiencing different levels of hazardous gas contamination revealed rational risk judgments by inhabitants of high-risk and moderate-risk communities, based on their perceived probability of contamination, probability of receiving impacts, and perceived catastrophic consequences. However, risks assessed by people in low-risk communities could not be rationally explained and were influenced by their collective experiences. PMID:24937530

Therapeutic peptides for cancer therapy. Part II - cell cycle inhibitory peptides and apoptosis-inducing peptides.

PubMed

Raucher, Drazen; Moktan, Shama; Massodi, Iqbal; Bidwell, Gene L

2009-10-01

Therapeutic peptides have great potential as anticancer agents owing to their ease of rational design and target specificity. However, their utility in vivo is limited by low stability and poor tumor penetration. The authors review the development of peptide inhibitors with potential for cancer therapy. Peptides that arrest the cell cycle by mimicking CDK inhibitors or induce apoptosis directly are discussed. The authors searched Medline for articles concerning the development of therapeutic peptides and their delivery. Inhibition of cancer cell proliferation directly using peptides that arrest the cell cycle or induce apoptosis is a promising strategy. Peptides can be designed that interact very specifically with cyclins and/or cyclin-dependent kinases and with members of apoptotic cascades. Use of these peptides is not limited by their design, as a rational approach to peptide design is much less challenging than the design of small molecule inhibitors of specific protein-protein interactions. However, the limitations of peptide therapy lie in the poor pharmacokinetic properties of these large, often charged molecules. Therefore, overcoming the drug delivery hurdles could open the door for effective peptide therapy, thus making an entirely new class of molecules useful as anticancer drugs.

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

PubMed

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 being conducted in academic, government and industrial laboratories. Furthermore, we apply our expertise in bioprocess to define a potential model for integration of these systems biology approaches into biologics development. © 2015 Wiley Periodicals, Inc.

In situ product removal in fermentation systems: improved process performance and rational extractant selection.

PubMed

Dafoe, Julian T; Daugulis, Andrew J

2014-03-01

The separation of inhibitory compounds as they are produced in biotransformation and fermentation systems is termed in situ product removal (ISPR). This review examines recent ISPR strategies employing several classes of extractants including liquids, solids, gases, and combined extraction systems. Improvement through the simple application of an auxiliary phase are tabulated and summarized to indicate the breadth of recent ISPR activities. Studies within the past 5 years that have highlighted and have discussed "second phase" properties, and that have an effect on fermentation performance, are particular focus of this review. ISPR, as a demonstrably effective processing strategy, continues to be widely adopted as more applications are explored; however, focus on the properties of extractants and their rational selection based on first principle considerations will likely be key to successfully applying ISPR to more challenging target molecules.

L-Cysteine Production in Escherichia coli Based on Rational Metabolic Engineering and Modular Strategy.

PubMed

Liu, Han; Fang, Guochen; Wu, Hui; Li, Zhimin; Ye, Qin

2018-05-01

L-cysteine is an amino acid with important physiological functions and has a wide range of applications in medicine, food, animal feed, and cosmetics industry. In this study, the L-cysteine synthesis in Escherichia coliEscherichia coli is divided into four modules: the transport module, sulfur module, precursor module, and degradation module. The engineered strain LH03 (overexpression of the feedback-insensitive cysE and the exporter ydeD in JM109) accumulated 45.8 mg L -1 of L-cysteine in 48 hr with yield of 0.4% g/g glucose. Further modifications of strains and culture conditions which based on the rational metabolic engineering and modular strategy improved the L-cysteine biosynthesis significantly. The engineered strain LH06 (with additional overexpression of serA, serC, and serB and double mutant of tnaA and sdaA in LH03) produced 620.9 mg L -1 of L-cysteine with yield of 6.0% g/g glucose, which increased the production by 12 times and the yield by 14 times more than those of LH03 in the original condition. In fed-batch fermentation performed in a 5-L reactor, the concentration of L-cysteine achieved 5.1 g L -1 in 32 hr. This work demonstrates that the combination of rational metabolic engineering and module strategy is a promising approach for increasing the L-cysteine production in E. coli. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Deep Rationality: The Evolutionary Economics of Decision Making.

PubMed

Kenrick, Douglas T; Griskevicius, Vladas; Sundie, Jill M; Li, Norman P; Li, Yexin Jessica; Neuberg, Steven L

2009-10-01

What is a "rational" decision? Economists traditionally viewed rationality as maximizing expected satisfaction. This view has been useful in modeling basic microeconomic concepts, but falls short in accounting for many everyday human decisions. It leaves unanswered why some things reliably make people more satisfied than others, and why people frequently act to make others happy at a cost to themselves. Drawing on an evolutionary perspective, we propose that people make decisions according to a set of principles that may not appear to make sense at the superficial level, but that demonstrate rationality at a deeper evolutionary level. By this, we mean that people use adaptive domain-specific decision-rules that, on average, would have resulted in fitness benefits. Using this framework, we re-examine several economic principles. We suggest that traditional psychological functions governing risk aversion, discounting of future benefits, and budget allocations to multiple goods, for example, vary in predictable ways as a function of the underlying motive of the decision-maker and individual differences linked to evolved life-history strategies. A deep rationality framework not only helps explain why people make the decisions they do, but also inspires multiple directions for future research.

Rational-Emotive Staff Development.

ERIC Educational Resources Information Center

Forman, Susan G.; Forman, Bruce D.

1980-01-01

The application of Rational-Emotive Therapy principles and techniques in in-service education for school personnel is discussed. Teacher and counselor participation in a staff development program is described. (Author)

Lebesgue measure and gambling

NASA Astrophysics Data System (ADS)

Kanoveĭ, V. G.; Linton, Tom; Uspensky, Vladimir A.

2008-12-01

Lebesgue measure of point sets is characterized in terms of the existence of various strategies in a certain coin-flipping game. 'Rational' and 'discrete' modifications of this game are investigated. We prove that if one of the players has a winning strategy in a game of this type depending on a given set P\\subseteq \\lbrack 0,1 \\rbrack , then this set is measurable. Bibliography: 11 titles.

Encountering Gender: Resisting a Neo-Liberal Political Rationality for Sexuality Education as an HIV Prevention Strategy

ERIC Educational Resources Information Center

Gacoin, Andrée E.

2017-01-01

Globally, sexuality education is framed as a key programmatic strategy for achieving HIV prevention among youth. In particular, sexuality education is positioned as a way to address gender inequalities and promote youth empowerment in relation to gendered identities. In this paper, I argue that the focus on what content should be taught and…

Engineering hybrid exosomes by membrane fusion with liposomes.

PubMed

Sato, Yuko T; Umezaki, Kaori; Sawada, Shinichi; Mukai, Sada-atsu; Sasaki, Yoshihiro; Harada, Naozumi; Shiku, Hiroshi; Akiyoshi, Kazunari

2016-02-25

Exosomes are a valuable biomaterial for the development of novel nanocarriers as functionally advanced drug delivery systems. To control and modify the performance of exosomal nanocarriers, we developed hybrid exosomes by fusing their membranes with liposomes using the freeze-thaw method. Exosomes embedded with a specific membrane protein isolated from genetically modified cells were fused with various liposomes, confirming that membrane engineering methods can be combined with genetic modification techniques. Cellular uptake studies performed using the hybrid exosomes revealed that the interactions between the developed exosomes and cells could be modified by changing the lipid composition or the properties of the exogenous lipids. These results suggest that the membrane-engineering approach reported here offers a new strategy for developing rationally designed exosomes as hybrid nanocarriers for use in advanced drug delivery systems.

Strategy selection in cue-based decision making.

PubMed

Bryant, David J

2014-06-01

People can make use of a range of heuristic and rational, compensatory strategies to perform a multiple-cue judgment task. It has been proposed that people are sensitive to the amount of cognitive effort required to employ decision strategies. Experiment 1 employed a dual-task methodology to investigate whether participants' preference for heuristic versus compensatory decision strategies can be altered by increasing the cognitive demands of the task. As indicated by participants' decision times, a secondary task interfered more with the performance of a heuristic than compensatory decision strategy but did not affect the proportions of participants using either type of strategy. A stimulus set effect suggested that the conjunction of cue salience and cue validity might play a determining role in strategy selection. The results of Experiment 2 indicated that when a perceptually salient cue was also the most valid, the majority of participants preferred a single-cue heuristic strategy. Overall, the results contradict the view that heuristics are more likely to be adopted when a task is made more cognitively demanding. It is argued that people employ 2 learning processes during training, one an associative learning process in which cue-outcome associations are developed by sampling multiple cues, and another that involves the sequential examination of single cues to serve as a basis for a single-cue heuristic.

Rational control of the interlayer space inside two-dimensional titanium carbides for highly efficient uranium removal and imprisonment.

PubMed

Wang, Lin; Tao, Wuqing; Yuan, Liyong; Liu, Zhirong; Huang, Qing; Chai, Zhifang; Gibson, John K; Shi, Weiqun

2017-11-07

Though two-dimensional early transition metal carbides and carbonitrides (MXenes) have attracted extensive interest recently, their superb abilities in various scientific applications always suffer from the very narrow interlayer space inside the multilayered structure. Here we demonstrate an unprecedented large adsorption capacity enhancement of Ti 3 C 2 T x toward radionuclide removal via a hydrated intercalation strategy. By rational control of the interlayer space, the potential for imprisoning the representative actinide U(vi) inside multilayered Ti 3 C 2 T x was also confirmed.

Assessment of seismic risk in Tashkent, Uzbekistan and Bishkek, Kyrgyz Republic

USGS Publications Warehouse

Erdik, M.; Rashidov, T.; Safak, E.; Turdukulov, A.

2005-01-01

The impact of earthquakes in urban centers prone to disastrous earthquakes necessitates the analysis of associated risk for rational formulation of contingency plans and mitigation strategies. In urban centers the seismic risk is best quantified and portrayed through the preparation of 'Earthquake damage and Loss Scenarios'. The components of such scenarios are the assessment of the hazard, inventories and the vulnerabilities of elements at risk. For the development of earthquake risk scenario in Tashkent-Uzbekistan and Bishkek-Kyrgyzstan an approach based on spectral displacements is utilized. This paper will present the important features of a comprehensive study, highlight the methodology, discuss the results and provide insights to the future developments. ?? 2005 Elsevier Ltd. All rights reserved.

The social problems and strategies of the government GIS in China

NASA Astrophysics Data System (ADS)

Chen, Nan; Fu, Zhongliang

2007-06-01

GIS has wider and wider applications. The application in the field of administrative management and assistant decision-making have formed a specific research area--the government GIS. As an information industry with great sociality, GIS and its development are influenced by many technical factors and social factors. As for the government GIS in China, the social factors often play a more important role in it. A description of the current development status of the government GIS, both in China and abroad, was made in this paper. After the description, researchers pointed out the deficiency of Chinese government GIS. On the basis of this, the rational suggestion of government GIS in China were put forward at last.

Cognitive impairment in older adults and oral health considerations: treatment and management.

PubMed

Brennan, Leonard J; Strauss, Jason

2014-10-01

Worldwide incidences of degenerative cognitive diseases are increasing as the population ages. This decline in mental function frequently causes behavioral changes that directly affect oral health. The loss of interest and ability to complete the simple tasks of brushing and flossing can cause a rapid development of hard and soft tissue diseases that result in decreased function and increased dental pain. The challenge for the dental community is to understand and to identify the early signs of cognitive dysfunction so as to develop a rational treatment strategy that allows patients to comfortably maintain their teeth for as long as possible. Copyright © 2014 Elsevier Inc. All rights reserved.

Rational Design and Facile Synthesis of Boranophosphate Ionic Liquids as Hypergolic Rocket Fuels.

PubMed

Liu, Tianlin; Qi, Xiujuan; Wang, Binshen; Jin, Yunhe; Yan, Chao; Wang, Yi; Zhang, Qinghua

2018-05-14

The design and synthesis of new hypergolic ionic liquids (HILs) as replacements for toxic hydrazine derivatives have been the focus of current academic research in the field of liquid bipropellant fuels. In most cases, however, the requirements of excellent ignition performances, good hydrolytic stabilities, and low synthetic costs are often contradictory, which makes the development of high-performance HILs an enormous challenge. Here, we show how a fuel-rich boranophosphate ion was rationally designed and used to synthesize a series of high-performance HILs with excellent comprehensive properties. In the design strategy, we introduced the {BH 3 } moiety into the boranophosphate ion for improving the self-ignition property, whereas the complexation of boron and phosphite was used to improve the hydrolytic activity of the borohydride species. As a result, these boranophosphate HILs exhibited wide liquid operating ranges (>220 °C), high densities (1.00-1.10 g cm -3 ), good hydrolytic stabilities, and short ignition delay times (2.3-9.7 milliseconds) with white fuming nitric acid (WFNA) as the oxidizer. More importantly, these boranophosphate HILs could be readily prepared in high yields from commercial phosphite esters, avoiding complex and time-consuming synthetic routes. This work offers an effective strategy of designing boranophosphate HILs towards safer and greener hypergolic fuels for liquid bipropellant applications. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Strategies toward High-Performance Cathode Materials for Lithium-Oxygen Batteries.

PubMed

Wang, Kai-Xue; Zhu, Qian-Cheng; Chen, Jie-Sheng

2018-05-11

Rechargeable aprotic lithium (Li)-O 2 batteries with high theoretical energy densities are regarded as promising next-generation energy storage devices and have attracted considerable interest recently. However, these batteries still suffer from many critical issues, such as low capacity, poor cycle life, and low round-trip efficiency, rendering the practical application of these batteries rather sluggish. Cathode catalysts with high oxygen reduction reaction (ORR) and evolution reaction activities are of particular importance for addressing these issues and consequently promoting the application of Li-O 2 batteries. Thus, the rational design and preparation of the catalysts with high ORR activity, good electronic conductivity, and decent chemical/electrochemical stability are still challenging. In this Review, the strategies are outlined including the rational selection of catalytic species, the introduction of a 3D porous structure, the formation of functional composites, and the heteroatom doping which succeeded in the design of high-performance cathode catalysts for stable Li-O 2 batteries. Perspectives on enhancing the overall electrochemical performance of Li-O 2 batteries based on the optimization of the properties and reliability of each part of the battery are also made. This Review sheds some new light on the design of highly active cathode catalysts and the development of high-performance lithium-O 2 batteries. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Novel Positron Emission Tomography (PET) Approach to Monitor Cardiac Metabolic Pathway Remodeling in Response to Sunitinib Malate.

PubMed

O'Farrell, Alice C; Evans, Rhys; Silvola, Johanna M U; Miller, Ian S; Conroy, Emer; Hector, Suzanne; Cary, Maurice; Murray, David W; Jarzabek, Monika A; Maratha, Ashwini; Alamanou, Marina; Udupi, Girish Mallya; Shiels, Liam; Pallaud, Celine; Saraste, Antti; Liljenbäck, Heidi; Jauhiainen, Matti; Oikonen, Vesa; Ducret, Axel; Cutler, Paul; McAuliffe, Fionnuala M; Rousseau, Jacques A; Lecomte, Roger; Gascon, Suzanne; Arany, Zoltan; Ky, Bonnie; Force, Thomas; Knuuti, Juhani; Gallagher, William M; Roivainen, Anne; Byrne, Annette T

2017-01-01

Sunitinib is a tyrosine kinase inhibitor approved for the treatment of multiple solid tumors. However, cardiotoxicity is of increasing concern, with a need to develop rational mechanism driven approaches for the early detection of cardiac dysfunction. We sought to interrogate changes in cardiac energy substrate usage during sunitinib treatment, hypothesising that these changes could represent a strategy for the early detection of cardiotoxicity. Balb/CJ mice or Sprague-Dawley rats were treated orally for 4 weeks with 40 or 20 mg/kg/day sunitinib. Cardiac positron emission tomography (PET) was implemented to investigate alterations in myocardial glucose and oxidative metabolism. Following treatment, blood pressure increased, and left ventricular ejection fraction decreased. Cardiac [18F]-fluorodeoxyglucose (FDG)-PET revealed increased glucose uptake after 48 hours. [11C]Acetate-PET showed decreased myocardial perfusion following treatment. Electron microscopy revealed significant lipid accumulation in the myocardium. Proteomic analyses indicated that oxidative metabolism, fatty acid β-oxidation and mitochondrial dysfunction were among the top myocardial signalling pathways perturbed. Sunitinib treatment results in an increased reliance on glycolysis, increased myocardial lipid deposition and perturbed mitochondrial function, indicative of a fundamental energy crisis resulting in compromised myocardial energy metabolism and function. Our findings suggest that a cardiac PET strategy may represent a rational approach to non-invasively monitor metabolic pathway remodeling following sunitinib treatment.

A Novel Positron Emission Tomography (PET) Approach to Monitor Cardiac Metabolic Pathway Remodeling in Response to Sunitinib Malate

PubMed Central

Silvola, Johanna M. U.; Miller, Ian S.; Conroy, Emer; Hector, Suzanne; Cary, Maurice; Murray, David W.; Jarzabek, Monika A.; Maratha, Ashwini; Alamanou, Marina; Udupi, Girish Mallya; Shiels, Liam; Pallaud, Celine; Saraste, Antti; Liljenbäck, Heidi; Jauhiainen, Matti; Oikonen, Vesa; Ducret, Axel; Cutler, Paul; McAuliffe, Fionnuala M.; Rousseau, Jacques A.; Lecomte, Roger; Gascon, Suzanne; Arany, Zoltan; Ky, Bonnie; Force, Thomas; Knuuti, Juhani; Gallagher, William M.; Roivainen, Anne; Byrne, Annette T.

2017-01-01

Sunitinib is a tyrosine kinase inhibitor approved for the treatment of multiple solid tumors. However, cardiotoxicity is of increasing concern, with a need to develop rational mechanism driven approaches for the early detection of cardiac dysfunction. We sought to interrogate changes in cardiac energy substrate usage during sunitinib treatment, hypothesising that these changes could represent a strategy for the early detection of cardiotoxicity. Balb/CJ mice or Sprague-Dawley rats were treated orally for 4 weeks with 40 or 20 mg/kg/day sunitinib. Cardiac positron emission tomography (PET) was implemented to investigate alterations in myocardial glucose and oxidative metabolism. Following treatment, blood pressure increased, and left ventricular ejection fraction decreased. Cardiac [18F]-fluorodeoxyglucose (FDG)-PET revealed increased glucose uptake after 48 hours. [11C]Acetate-PET showed decreased myocardial perfusion following treatment. Electron microscopy revealed significant lipid accumulation in the myocardium. Proteomic analyses indicated that oxidative metabolism, fatty acid β-oxidation and mitochondrial dysfunction were among the top myocardial signalling pathways perturbed. Sunitinib treatment results in an increased reliance on glycolysis, increased myocardial lipid deposition and perturbed mitochondrial function, indicative of a fundamental energy crisis resulting in compromised myocardial energy metabolism and function. Our findings suggest that a cardiac PET strategy may represent a rational approach to non-invasively monitor metabolic pathway remodeling following sunitinib treatment. PMID:28129334

RATIONAL APPROXIMATIONS TO GENERALIZED HYPERGEOMETRIC FUNCTIONS.

DTIC Science & Technology

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

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

PubMed

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.

Modeling Sexual Selection in Túngara Frog and Rationality of Mate Choice.

PubMed

Vargas Bernal, Esteban; Sanabria Malagon, Camilo

2017-12-01

The males of the species of frogs Engystomops pustulosus produce simple and complex calls to lure females, as a way of intersexual selection. Complex calls lead males to a greater reproductive success than what simple calls do. However, the complex calls are also more attractive to their main predator, the bat Trachops cirrhosus. Therefore, as M. Ryan suggests in (The túngara frog: a study in sexual selection and communication. University of Chicago Press, Chicago, 1985), the complexity of the calls lets the frogs keep a trade-off between reproductive success and predation. In this paper, we verify this trade-off from the perspective of game theory. We first model the proportion of simple calls as a symmetric game of two strategies. We also model the effect of adding a third strategy, males that keep quiet and intercept females, which would play a role of intrasexual selection. Under the assumption that the decision of the males takes into account this trade-off between reproductive success and predation, our model reproduces the observed behavior reported in the literature with minimal assumption on the parameters. From the model with three strategies, we verify that the quiet strategy could only coexists with the simple and complex strategies if the rate at which quiet males intercept females is high, which explains the rarity of the quiet strategy. We conclude that the reproductive strategy of the male frog E. pustulosus is rational.

Societal Change: Via Violence or "Peaceful Revolution"?

ERIC Educational Resources Information Center

Williamson, E. G.

1975-01-01

Discusses the role of Student Personnel Services in aiding students to identify and evaluate, through rational dialogue, the "causal variables" of human misery and degradation as the strategy of their preparation to innovate societal change. (Author)

Identifying regional opportunities for accelerated timber managemnet

Treesearch

David A. Gansner; Joseph E. Barnard; Samuel F. Gingrich; Samuel F. Gingrich

1973-01-01

Describes a procedure for identifying regional opportunities for accelerated timber management and demonstrates its application. Results provide a basis for rational choices among alternative management strategies and permit meaningful micro- and macro-evaluations of treatment response.

Rationality in medicine: an explication.

PubMed

Gert, B; Clouser, K D

1986-05-01

Various meanings of "rational" implicitly and explicitly suggested in this issue's articles are abstracted and stated. Two accounts of rationality are shown to be able to explain most uses of "rational": the "cool moment" account and a more objective account. The former is examined and modified, but still found inadequate. The objective account of rational is developed, taking "irrational" as the basic concept. "Irrational" is given content in terms of a list, and "rational" is subsequently defined as "not irrational". Reasons and motives are defined and distinguished. The advantages of the objective account are explored and some challenges to it are answered.

Community attitudes toward rationing ARVs: a qualitative study of justice and equity.

PubMed

Rennie, Stuart

2006-12-01

Medical rationing of anti-retroviral therapies (ARVs) may conflict with the right to health, but rationing is nevertheless a reality in developing countries. In this article, which is based on a poster presentation at the conference, Stuart Rennie presents the preliminary findings of a study on community attitudes towards rationing ARVs in the Democratic Republic of Congo (DRC).

Teaching for rationality: What does it mean for preservice middle level teachers' intellectual development?

NASA Astrophysics Data System (ADS)

Kleine, Karynne L. M.

The conception of intellectual development has undergone considerable change since Perry's influential study of undergraduates in 1968. Most notably, theorists have tried to account for the fact that women do not appear to be as intellectually developed as men when examined through traditional models that emphasize the use of impersonal and distanced objectivity and logic by acknowledging that rationality may include aspects of emotionalism and subjectivity. One model that shows potential to accurately describe the development of women is presented by Belenky, Clinchy, Goldberger and Tarule (1986). An important application of this development, which holds promise for successful education reform efforts, is the ability to improve the intellectual development of preservice middle level teachers through their teacher preparation programs. Thus, this study sought to (a) examine through case studies the intellectual development of five selected female and male members of a cohort of preservice middle level teachers at Rotunda College (not its real name) exposed to a ten week course emphasizing the use of rationality in various impersonal and relational ways as they developed their teaching practices, and (b) determine whether these preservice teachers came to value rationality as a means to becoming an excellent teacher. This was accomplished by conducting a mixedgender test of the model of intellectual development proposed by Belenky et al. (1986), and by using interviews, questionnaires, and artifacts to note their conceptual changes and changes in their valuing of rationality that occurred over the period of the course. The present study also evaluated Rotunda College's achievement of several aspects of its liberal arts mission. Analysis of qualitative and quantitative data for five case study participants indicates that fostering rationality in preservice middle level teachers through various impersonal and relational ways advances the desire to develop intellectually and supports intellectual growth as shown on measures of intellectual development. Two young, female participants did not demonstrate the high levels or accelerated rates of intellectual development of the other participants, suggesting that there is more work needed in this area to understand the phenomenon of utilizing relational learning environments. Also, the case study students' enhancement of their rational behaviors suggests that Rotunda College, by promoting rationality in a number of ways in its teacher preparation program, successfully imbues those undergraduates with critical aspects of a liberal arts education.

Using Art to Teach Students Science Outdoors: How Creative Science Instruction Influences Observation, Question Formation, and Involvement

NASA Astrophysics Data System (ADS)

Cone, Christina Schull

Elementary education has become increasingly divided into subjects and focused on the demand for high math and reading scores. Consequently, teachers spend less time devoted to science and art instruction. However, teaching art and science is crucial to developing creative and rational thinking, especially for observation and questioning skills. In this study, third grade students attending an urban school in Portland, Oregon received instruction of an art strategy using observational and quantifying drawing techniques. This study examines, "Will an art strategy observing the local environment help students make observations and ask questions?" and "In what ways are student learning and perspectives of science affected by the art strategy?" The independent variable is the art strategy developed for this study. There are three dependent variables: quality of student observations, quality of questions, and themes on student learning and perspectives of science. I predicted students would develop strong observation and questioning skills and that students would find the strategy useful or have an increased interest in science. The art scores were high for relevance and detail, but not for text. There were significant correlations between art scores and questions. Interviews revealed three themes: observations create questions, drawing is helpful and challenging, and students connected to science. By examining science through art, students were engaged and created strong observations and questions. Teachers need to balance unstructured drawing time with scaffolding for optimal results. This study provides an integrated science and art strategy that teachers can use outdoors or adapt for the classroom.

Rational temporal predictions can underlie apparent failures to delay gratification.

PubMed

McGuire, Joseph T; Kable, Joseph W

2013-04-01

An important category of seemingly maladaptive decisions involves failure to postpone gratification. A person pursuing a desirable long-run outcome may abandon it in favor of a short-run alternative that has been available all along. Here we present a theoretical framework in which this seemingly irrational behavior emerges from stable preferences and veridical judgments. Our account recognizes that decision makers generally face uncertainty regarding the time at which future outcomes will materialize. When timing is uncertain, the value of persistence depends crucially on the nature of a decision maker's prior temporal beliefs. Certain forms of temporal beliefs imply that a delay's predicted remaining length increases as a function of time already waited. In this type of situation, the rational, utility-maximizing strategy is to persist for a limited amount of time and then give up. We show empirically that people's explicit predictions of remaining delay lengths indeed increase as a function of elapsed time in several relevant domains, implying that temporal judgments offer a rational basis for limiting persistence. We then develop our framework into a simple working model and show how it accounts for individual differences in a laboratory task (the well-known "marshmallow test"). We conclude that delay-of-gratification failure, generally viewed as a manifestation of limited self-control capacity, can instead arise as an adaptive response to the perceived statistics of one's environment.

Rational temporal predictions can underlie apparent failures to delay gratification

PubMed Central

McGuire, Joseph T.; Kable, Joseph W.

2013-01-01

An important category of seemingly maladaptive decisions involves failure to postpone gratification. A person pursuing a desirable long-run outcome may abandon it in favor of a short-run alternative that has been available all along. Here we present a theoretical framework in which this seemingly irrational behavior emerges from stable preferences and veridical judgments. Our account recognizes that decision makers generally face uncertainty regarding the time at which future outcomes will materialize. When timing is uncertain, the value of persistence depends crucially on the nature of a decision-maker’s prior temporal beliefs. Certain forms of temporal beliefs imply that a delay’s predicted remaining length increases as a function of time already waited. In this type of situation, the rational, utility-maximizing strategy is to persist for a limited amount of time and then give up. We show empirically that people’s explicit predictions of remaining delay lengths indeed increase as a function of elapsed time in several relevant domains, implying that temporal judgments offer a rational basis for limiting persistence. We then develop our framework into a simple working model and show how it accounts for individual differences in a laboratory task (the well-known “marshmallow test”). We conclude that delay-of-gratification failure, generally viewed as a manifestation of limited self-control capacity, can instead arise as an adaptive response to the perceived statistics of one’s environment. PMID:23458085

Polymeric micelles: nanocarriers for cancer-targeted drug delivery.

PubMed

Zhang, Yifei; Huang, Yixian; Li, Song

2014-08-01

Polymeric micelles represent an effective delivery system for poorly water-soluble anticancer drugs. With small size (10-100 nm) and hydrophilic shell of PEG, polymeric micelles exhibit prolonged circulation time in the blood and enhanced tumor accumulation. In this review, the importance of rational design was highlighted by summarizing the recent progress on the development of micellar formulations. Emphasis is placed on the new strategies to enhance the drug/carrier interaction for improved drug-loading capacity. In addition, the micelle-forming drug-polymer conjugates are also discussed which have both drug-loading function and antitumor activity.

The development of bis(hydroxymethyl)pyrrole analogs as bifunctional DNA cross-linking agents and their chemotherapeutic potential.

PubMed

Su, Tsann-Long; Lee, Te-Chang; Kakadiya, Rajesh

2013-11-01

Bifunctional DNA cross-linking agents are widely used as chemotherapeutic agents in clinics. The advance in the development of these agents as potential antitumor agents has generated various types of bis(hydroxymethyl)pyrrole analogs. In order to develop highly effective anticancer agents, it is necessary to understand the chemophysical properties, structure-activity relationships, therapeutic potency, toxicity/safety, and pharmacokinetics of these DNA cross-linking agents. This review presents an overview of the recent advances in developing various types of bis(hydroxymethyl)pyrrole analogs with potential antitumor activity to provide more information for future drug design and strategies for combination chemotherapy. The rational drug design, chemical syntheses, antitumor activity, mechanism of action, and development of combined chemotherapy regimens, including a DNA repair inhibitor, are discussed. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Integrated testing strategies can be optimal for chemical risk classification.

PubMed

Raseta, Marko; Pitchford, Jon; Cussens, James; Doe, John

2017-08-01

There is an urgent need to refine strategies for testing the safety of chemical compounds. This need arises both from the financial and ethical costs of animal tests, but also from the opportunities presented by new in-vitro and in-silico alternatives. Here we explore the mathematical theory underpinning the formulation of optimal testing strategies in toxicology. We show how the costs and imprecisions of the various tests, and the variability in exposures and responses of individuals, can be assembled rationally to form a Markov Decision Problem. We compute the corresponding optimal policies using well developed theory based on Dynamic Programming, thereby identifying and overcoming some methodological and logical inconsistencies which may exist in the current toxicological testing. By illustrating our methods for two simple but readily generalisable examples we show how so-called integrated testing strategies, where information of different precisions from different sources is combined and where different initial test outcomes lead to different sets of future tests, can arise naturally as optimal policies. Copyright © 2017 Elsevier Inc. All rights reserved.

Systematic development of small molecules to inhibit specific microscopic steps of Aβ42 aggregation in Alzheimer’s disease

PubMed Central

Habchi, Johnny; Chia, Sean; Limbocker, Ryan; Mannini, Benedetta; Ahn, Minkoo; Perni, Michele; Hansson, Oskar; Arosio, Paolo; Kumita, Janet R.; Challa, Pavan Kumar; Cohen, Samuel I. A.; Dobson, Christopher M.; Knowles, Tuomas P. J.; Vendruscolo, Michele

2017-01-01

The aggregation of the 42-residue form of the amyloid-β peptide (Aβ42) is a pivotal event in Alzheimer’s disease (AD). The use of chemical kinetics has recently enabled highly accurate quantifications of the effects of small molecules on specific microscopic steps in Aβ42 aggregation. Here, we exploit this approach to develop a rational drug discovery strategy against Aβ42 aggregation that uses as a read-out the changes in the nucleation and elongation rate constants caused by candidate small molecules. We thus identify a pool of compounds that target specific microscopic steps in Aβ42 aggregation. We then test further these small molecules in human cerebrospinal fluid and in a Caenorhabditis elegans model of AD. Our results show that this strategy represents a powerful approach to identify systematically small molecule lead compounds, thus offering an appealing opportunity to reduce the attrition problem in drug discovery. PMID:28011763

Cell-Free Protein Synthesis Enhancement from Real-Time NMR Metabolite Kinetics: Redirecting Energy Fluxes in Hybrid RRL Systems.

PubMed

Panthu, Baptiste; Ohlmann, Théophile; Perrier, Johan; Schlattner, Uwe; Jalinot, Pierre; Elena-Herrmann, Bénédicte; Rautureau, Gilles J P

2018-01-19

A counterintuitive cell-free protein synthesis (CFPS) strategy, based on reducing the ribosomal fraction in rabbit reticulocyte lysate (RRL), triggers the development of hybrid systems composed of RRL ribosome-free supernatant complemented with ribosomes from different mammalian cell-types. Hybrid RRL systems maintain translational properties of the original ribosome cell types, and deliver protein expression levels similar to RRL. Here, we show that persistent ribosome-associated metabolic activity consuming ATP is a major obstacle for maximal protein yield. We provide a detailed picture of hybrid CFPS systems energetic metabolism based on real-time nuclear magnetic resonance (NMR) investigation of metabolites kinetics. We demonstrate that protein synthesis capacity has an upper limit at native ribosome concentration and that lower amounts of the ribosomal fraction optimize energy fluxes toward protein translation, consequently increasing CFPS yield. These results provide a rationalized strategy for further mammalian CFPS developments and reveal the potential of real-time NMR metabolism phenotyping for optimization of cell-free protein expression systems.

The neural basis of financial risk taking.

PubMed

Kuhnen, Camelia M; Knutson, Brian

2005-09-01

Investors systematically deviate from rationality when making financial decisions, yet the mechanisms responsible for these deviations have not been identified. Using event-related fMRI, we examined whether anticipatory neural activity would predict optimal and suboptimal choices in a financial decision-making task. We characterized two types of deviations from the optimal investment strategy of a rational risk-neutral agent as risk-seeking mistakes and risk-aversion mistakes. Nucleus accumbens activation preceded risky choices as well as risk-seeking mistakes, while anterior insula activation preceded riskless choices as well as risk-aversion mistakes. These findings suggest that distinct neural circuits linked to anticipatory affect promote different types of financial choices and indicate that excessive activation of these circuits may lead to investing mistakes. Thus, consideration of anticipatory neural mechanisms may add predictive power to the rational actor model of economic decision making.

Engineering of isoamylase: improvement of protein stability and catalytic efficiency through semi-rational design.

PubMed

Li, Youran; Zhang, Liang; Ding, Zhongyang; Gu, Zhenghua; Shi, Guiyang

2016-01-01

Isoamylase catalyzes the hydrolysis of α-1,6-glycosidic linkages in glycogen, amylopectin and α/β-limit dextrins. A semi-rational design strategy was performed to improve catalytic properties of isoamylase from Bacillus lentus. Three residues in vicinity of the essential residues, Arg505, Asn513, and Gly608, were chosen as the mutation sites and were substituted by Ala, Pro, Glu, and Lys, respectively. Thermal stability of the mutant R505P and acidic stability of the mutant R505E were enhanced. The k cat /K m values of the mutant G608V have been promoted by 49%, and the specific activity increased by 33%. This work provides an effective strategy for improving the catalytic activity and stability of isoamylase, and the results obtained here may be useful for the improvement of catalytic properties of other α/β barrel enzymes.

The Rational Adolescent: Strategic Information Processing during Decision Making Revealed by Eye Tracking.

PubMed

Kwak, Youngbin; Payne, John W; Cohen, Andrew L; Huettel, Scott A

2015-01-01

Adolescence is often viewed as a time of irrational, risky decision-making - despite adolescents' competence in other cognitive domains. In this study, we examined the strategies used by adolescents (N=30) and young adults (N=47) to resolve complex, multi-outcome economic gambles. Compared to adults, adolescents were more likely to make conservative, loss-minimizing choices consistent with economic models. Eye-tracking data showed that prior to decisions, adolescents acquired more information in a more thorough manner; that is, they engaged in a more analytic processing strategy indicative of trade-offs between decision variables. In contrast, young adults' decisions were more consistent with heuristics that simplified the decision problem, at the expense of analytic precision. Collectively, these results demonstrate a counter-intuitive developmental transition in economic decision making: adolescents' decisions are more consistent with rational-choice models, while young adults more readily engage task-appropriate heuristics.

The Rational Adolescent: Strategic Information Processing during Decision Making Revealed by Eye Tracking

PubMed Central

Kwak, Youngbin; Payne, John W.; Cohen, Andrew L.; Huettel, Scott A.

2015-01-01

Adolescence is often viewed as a time of irrational, risky decision-making – despite adolescents' competence in other cognitive domains. In this study, we examined the strategies used by adolescents (N=30) and young adults (N=47) to resolve complex, multi-outcome economic gambles. Compared to adults, adolescents were more likely to make conservative, loss-minimizing choices consistent with economic models. Eye-tracking data showed that prior to decisions, adolescents acquired more information in a more thorough manner; that is, they engaged in a more analytic processing strategy indicative of trade-offs between decision variables. In contrast, young adults' decisions were more consistent with heuristics that simplified the decision problem, at the expense of analytic precision. Collectively, these results demonstrate a counter-intuitive developmental transition in economic decision making: adolescents' decisions are more consistent with rational-choice models, while young adults more readily engage task-appropriate heuristics. PMID:26388664

Toward rational design of electrical stimulation strategies for epilepsy control

PubMed Central

Sunderam, Sridhar; Gluckman, Bruce; Reato, Davide; Bikson, Marom

2009-01-01

Electrical stimulation is emerging as a viable alternative for epilepsy patients whose seizures are not alleviated by drugs or surgery. Its attractions are temporal and spatial specificity of action, flexibility of waveform parameters and timing, and the perception that its effects are reversible unlike resective surgery. However, despite significant advances in our understanding of mechanisms of neural electrical stimulation, clinical electrotherapy for seizures relies heavily on empirical tuning of parameters and protocols. We highlight concurrent treatment goals with potentially conflicting design constraints that must be resolved when formulating rational strategies for epilepsy electrotherapy: namely seizure reduction versus cognitive impairment, stimulation efficacy versus tissue safety, and mechanistic insight versus clinical pragmatism. First, treatment markers, objectives, and metrics relevant to electrical stimulation for epilepsy are discussed from a clinical perspective. Then the experimental perspective is presented, with the biophysical mechanisms and modalities of open-loop electrical stimulation, and the potential benefits of closed-loop control for epilepsy. PMID:19926525

[Algorithms for treatment of complex hand injuries].

PubMed

Pillukat, T; Prommersberger, K-J

2011-07-01

The primary treatment strongly influences the course and prognosis of hand injuries. Complex injuries which compromise functional recovery are especially challenging. Despite an apparently unlimited number of injury patterns it is possible to develop strategies which facilitate a standardized approach to operative treatment. In this situation algorithms can be important guidelines for a rational approach. The following algorithms have been proven in the treatment of complex injuries of the hand by our own experience. They were modified according to the current literature and refer to prehospital care, emergency room management, basic strategy in general and reconstruction of bone and joints, vessels, nerves, tendons and soft tissue coverage in detail. Algorithms facilitate the treatment of severe hand injuries. Applying simple yes/no decisions complex injury patterns are split into distinct partial problems which can be managed step by step.

Teaching physics as a service subject

NASA Astrophysics Data System (ADS)

Lowe, T. L.; Hayes, M.

1986-07-01

At South Glamorgan Institute of Higher Education physics is taught over a wide range of courses. In addition to the more conventional courses found in science, technology and education faculties there is a physics input into areas such as beauty therapy, applied biology, catering, chiropody, dental technology, environmental health, food technology, hairdressing, human-movement studies, industrial design, applied life sciences, marine technology, medical laboratory science, physiological measurement, nursing and speech therapy. Due to the fundamental differences in emphasis required when teaching physics as a 'minor' subject on these types of courses, and since the authors have no courses which lead to a 'major' physics qualification, it is necessary to develop a rational strategy for teaching physics as a 'service' subject. If this is not achieved then staff satisfaction and student interest are likely to suffer. They describe their strategy.

NEW RATION CONCEPTS.

DTIC Science & Technology

A ration for use in the Office of Civil Defense ration program was developed. The product was formulated from whole wheat flour, casein, baking ...powder, sodium chloride, sucrose, fat, yeast , water, and small amounts of other ingredients. A daily portion contained 900 calories and 18.5% protein

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

PubMed

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

2014-08-21

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

Action Being Character: A Promising Perspective on the Solution Concept of Game Theory

PubMed Central

Deng, Kuiying; Chu, Tianguang

2011-01-01

The inconsistency of predictions from solution concepts of conventional game theory with experimental observations is an enduring question. These solution concepts are based on the canonical rationality assumption that people are exclusively self-regarding utility maximizers. In this article, we think this assumption is problematic and, instead, assume that rational economic agents act as if they were maximizing their implicit utilities, which turns out to be a natural extension of the canonical rationality assumption. Implicit utility is defined by a player's character to reflect his personal weighting between cooperative, individualistic, and competitive social value orientations. The player who actually faces an implicit game chooses his strategy based on the common belief about the character distribution for a general player and the self-estimation of his own character, and he is not concerned about which strategies other players will choose and will never feel regret about his decision. It is shown by solving five paradigmatic games, the Dictator game, the Ultimatum game, the Prisoner's Dilemma game, the Public Goods game, and the Battle of the Sexes game, that the framework of implicit game and its corresponding solution concept, implicit equilibrium, based on this alternative assumption have potential for better explaining people's actual behaviors in social decision making situations. PMID:21573055

Action being character: a promising perspective on the solution concept of game theory.

PubMed

Deng, Kuiying; Chu, Tianguang

2011-05-09

The inconsistency of predictions from solution concepts of conventional game theory with experimental observations is an enduring question. These solution concepts are based on the canonical rationality assumption that people are exclusively self-regarding utility maximizers. In this article, we think this assumption is problematic and, instead, assume that rational economic agents act as if they were maximizing their implicit utilities, which turns out to be a natural extension of the canonical rationality assumption. Implicit utility is defined by a player's character to reflect his personal weighting between cooperative, individualistic, and competitive social value orientations. The player who actually faces an implicit game chooses his strategy based on the common belief about the character distribution for a general player and the self-estimation of his own character, and he is not concerned about which strategies other players will choose and will never feel regret about his decision. It is shown by solving five paradigmatic games, the Dictator game, the Ultimatum game, the Prisoner's Dilemma game, the Public Goods game, and the Battle of the Sexes game, that the framework of implicit game and its corresponding solution concept, implicit equilibrium, based on this alternative assumption have potential for better explaining people's actual behaviors in social decision making situations.

Can rational models be good accounts of developmental change? The case of language development at two time scales.

PubMed

Dawson, Colin R; Gerken, LouAnn

2012-01-01

Rational models of human perception and cognition have allowed researchers new ways to look at learning and the ability to make inferences from data. But how good are such models at accounting for developmental change? In this chapter, we address this question in the domain of language development, focusing on the speed with which developmental change takes place, and classifying different types of language development as either fast or slow. From the pattern of fast and slow development observed, we hypothesize that rational learning processes are generally well suited for handling fast processes over small amounts of input data. In contrast, we suggest that associative learning processes are generally better suited to slow development, in which learners accumulate information about what is typical of their language over time. Finally, although one system may be dominant for a particular component of language learning, we speculate that both systems frequently interact, with the associative system providing a source of emergent hypotheses to be evaluated by the rational system and the rational system serving to highlight which aspects of the learner's input need to be processed in greater depth by the associative system.

Problem Solving: Helping Students Move From Novices Toward Experts

NASA Astrophysics Data System (ADS)

Harper, Kathleen A.

2010-10-01

When introductory physics students engage in problem solving, they often exhibit behaviors that can frustrate their teachers. Some well-known examples of these habits include refusing to draw free-body diagrams, hunting through the book to find an example problem to use as a (perhaps inappropriate) template, and the classic ``plug-n-chug'' mentality. Studies in science education and cognitive science have yielded rational explanations for many of these novice behaviors and lay a groundwork for instructors to aid their students in beginning to develop more expert-like skills and behaviors. A few examples of these studies, as well as curricular tools that have developed as a result, will be shared. These tools not only encourage students to try more expert-like strategies, but also prime them for developing conceptual understanding.

Promoting the energy structure optimization around Chinese Beijing-Tianjin area by developing biomass energy

NASA Astrophysics Data System (ADS)

Zhao, Li; Sun, Du; Wang, Shi-Yu; Zhao, Feng-Qing

2017-06-01

In recent years, remarkable achievements in the utilization of biomass energy have been made in China. However, there are still some problems, such as irrational industry layout, immature existing market survival mechanism and lack of core competitiveness. On the basis of investigation and research, some recommendations and strategies are proposed for the development of biomass energy around Chinese Beijing-Tianjin area: scientific planning and precise laying out of biomass industry; rationalizing the relationship between government and enterprises and promoting the establishment of a market-oriented survival mechanism; combining ‘supply side’ with ‘demand side’ to optimize product structure; extending industrial chain to promote industry upgrading and sustainable development; and comprehensive co-ordinating various types of biomass resources and extending product chain to achieve better economic benefits.

Estimation of parameters in rational reaction rates of molecular biological systems via weighted least squares

NASA Astrophysics Data System (ADS)

Wu, Fang-Xiang; Mu, Lei; Shi, Zhong-Ke

2010-01-01

The models of gene regulatory networks are often derived from statistical thermodynamics principle or Michaelis-Menten kinetics equation. As a result, the models contain rational reaction rates which are nonlinear in both parameters and states. It is challenging to estimate parameters nonlinear in a model although there have been many traditional nonlinear parameter estimation methods such as Gauss-Newton iteration method and its variants. In this article, we develop a two-step method to estimate the parameters in rational reaction rates of gene regulatory networks via weighted linear least squares. This method takes the special structure of rational reaction rates into consideration. That is, in the rational reaction rates, the numerator and the denominator are linear in parameters. By designing a special weight matrix for the linear least squares, parameters in the numerator and the denominator can be estimated by solving two linear least squares problems. The main advantage of the developed method is that it can produce the analytical solutions to the estimation of parameters in rational reaction rates which originally is nonlinear parameter estimation problem. The developed method is applied to a couple of gene regulatory networks. The simulation results show the superior performance over Gauss-Newton method.

Rationalizing the Promotion of Non-Rational Behaviors in Organizations.

ERIC Educational Resources Information Center

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)

The Role of Rationality in Transformative Education

ERIC Educational Resources Information Center

Arends, Jessica

2014-01-01

As scholars, we are responsible for examining the academic and pedagogical traditions from which our current approaches have developed. This includes the historical establishment of and reliance upon rationality which postmodernist scholarship argues unconsciously guides our educational motives and processes. Rationality is especially relevant to…

Rapid humanitarian assessments and rationality: a value-of-information study from Iraq, 2003-04.

PubMed

Benini, Aldo; Conley, Charles

2007-03-01

Rapid assessments are one of the standard informational tools in humanitarian response and are supposed to contribute to rational decision-making.(1) The extent to which the assessment organisation itself behaves rationally, however, is an open question. This can be evaluated against multiple criteria, such as the cost and value of the information it collects and its ability to adapt flexibly design or samples when the survey environment changes unforeseeably. An unusual data constellation from two concurrent recent (2003-04) rapid assessments in northern Iraq permits us to model part of the actual assessment behaviour in terms of geographical, community and prior substantive information attributes. The model correctly predicts the decisions, in 79 per cent of the 2,425 local communities in focus, that data collector teams in the Emergency Mine Action Survey made to visit or not to visit. The analysis demonstrates variably rational behaviour under conditions of insecurity, repeated regrouping and incomplete sampling frames. A pronounced bias towards very small rural settlements is irrational for the overall results, but may be a rational strategy of individual survey workers seeking to prolong their employment. Implications for future assessments are sketched in the areas of tools for urban surveys, greater adaptability, including early feedback from users, and sensibility to value-of-information concepts.

Working with the private sector for child health.

PubMed

Waters, Hugh; Hatt, Laurel; Peters, David

2003-06-01

Private sector providers are the most commonly consulted source of care for child illnesses in many countries, offering significant opportunities to expand the reach of essential child health services and products. Yet collaboration with private providers presents major challenges - the suitability and quality of the services they provide is often questionable and governments' capacity to regulate them is limited. This article assesses the actual and potential contributions of the private sector to child health, and classifies and evaluates public sector strategies to promote and rationalize the contributions of private sector actors. Governments and international organizations can use a variety of strategies to collaborate with and influence private sector actors to improve child health - including contracting, regulating, financing and social marketing, training, coordinating and informing the public. These mutually reinforcing strategies can both improve the quality of services currently delivered in the private sector, and expand and rationalize the coverage of these services. One lesson from this review is that the private sector is very heterogeneous. At the country level, feasible strategies depend on the potential of the different components of the private sector and the capacity of governments and their partners for collaboration. To date, experience with private sector strategies offers considerable promise for children's health, but also raises many questions about the feasibility and impact of these strategies. Where possible, future interventions should be designed as experiments, with careful assessment of the intervention design and the environment in which they are implemented.

Literature search strategies for conducting knowledge-building and theory-generating qualitative systematic reviews.

PubMed

Finfgeld-Connett, Deborah; Johnson, E Diane

2013-01-01

To report literature search strategies for the purpose of conducting knowledge-building and theory-generating qualitative systematic reviews. Qualitative systematic reviews lie on a continuum from knowledge-building and theory-generating to aggregating and summarizing. Different types of literature searches are needed to optimally support these dissimilar reviews. Articles published between 1989-Autumn 2011. These documents were identified using a hermeneutic approach and multiple literature search strategies. Redundancy is not the sole measure of validity when conducting knowledge-building and theory-generating systematic reviews. When conducting these types of reviews, literature searches should be consistent with the goal of fully explicating concepts and the interrelationships among them. To accomplish this objective, a 'berry picking' approach is recommended along with strategies for overcoming barriers to finding qualitative research reports. To enhance integrity of knowledge-building and theory-generating systematic reviews, reviewers are urged to make literature search processes as transparent as possible, despite their complexity. This includes fully explaining and rationalizing what databases were used and how they were searched. It also means describing how literature tracking was conducted and grey literature was searched. In the end, the decision to cease searching also needs to be fully explained and rationalized. Predetermined linear search strategies are unlikely to generate search results that are adequate for purposes of conducting knowledge-building and theory-generating qualitative systematic reviews. Instead, it is recommended that iterative search strategies take shape as reviews evolve. © 2012 Blackwell Publishing Ltd.

Current status and future prospects of the development of clinical Pharmacy in China: A SWOT analysis.

PubMed

Rao, Yuefeng; Zhao, Qingwei; Zhang, Xiangyi; Yang, Hongyu; Lou, Yan; Zhang, Xingguo

2016-03-01

In many industrialized countries, clinical pharmacy has developed into a separate discipline and become a vital part of inpatient care in hospitals. However, as compared to many established branches of medicine, clinical pharmacy is still in its infancy, with much room for growth, improvement, and recognition by both the medical community and patients. In this study, a widely-recognized development strategy analysis tool, Strength, Weakness, Opportunity and Threat (SWOT), was used to systematically address several key issues to the development of clinical pharmacy in China. This analysis aims to provide feasible recommendations for the development of clinical pharmacy in China by identifying current problems and growth opportunities. Full development of clinical pharmacy as a mature clinical discipline will help promote the rational use of drugs by both clinicians and patients and lead to enhanced drug efficacy and safety.

Message strategies in direct-to-consumer pharmaceutical advertising: a content analysis using Taylor's six-segment message strategy wheel.

PubMed

Tsai, Wan-Hsiu Sunny; Lancaster, Alyse R

2012-01-01

This exploratory study applies Taylor's (1999) six-segment message strategy wheel to direct-to-consumer (DTC) pharmaceutical television commercials to understand message strategies adopted by pharmaceutical advertisers to persuade consumers. A convenience sample of 96 DTC commercial campaigns was analyzed. The results suggest that most DTC drug ads used a combination approach, providing consumers with medical and drug information while simultaneously appealing to the viewer's ego-related needs and desires. In contrast to ration and ego strategies, other approaches including routine, acute need, and social are relatively uncommon while sensory was the least common message strategy. Findings thus recognized the educational value of DTC commercials.

School Counselors and Psychological Aspects of Learning Disabilities.

ERIC Educational Resources Information Center

Fahey, David A.

1984-01-01

Provides an overview of some of the more common psychological theories and behavioral variables associated with learning disabilities. Reviews Adlerian Rational Emotive and behavioral and hypnotherapy approaches as intervention strategies for the counselor confronted with learning disabled students. (LLL)

To Be or Not to Be?: A Method for Evaluating Academic Support Units.

ERIC Educational Resources Information Center

Cohn, Roy E.

1979-01-01

Reasons for the budget cut vulnerability of instructional support agencies and the haphazard, capricious criteria often used to judge their effectiveness are discussed. An evaluation strategy for rational decision-making is proposed. (Author/PHR)

[Rational use of psychotropic drugs and social communication role].

PubMed

Montero, F

1994-06-01

Extra-clinical factors about the influences affecting the prescription and use of drugs are reviewed. Special attention is given to regulatory agencies, the pharmaceutical industry, and mass media. The problems and public health consequences of the irrational use of drugs are rarely documented in Latin America. Analysis of these factors, information sources, and rational use of psychotropic drugs will require multiple strategies such as social communication and policy formulation to define goals and objectives related to population information, doctors' and individual citizens' decision making processes, and participation of consumers in improving the use of psychotropic drugs.

Oligoalanine helical callipers for cell penetration.

PubMed

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

2018-06-04

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

Optimization through satisficing with prospects

NASA Astrophysics Data System (ADS)

Oyo, Kuratomo; Takahashi, Tatsuji

2017-07-01

As the broadening scope of reinforcement learning calls for a rational and more efficient heuristics, we test a satisficing strategy named RS, based on the theory of bounded rationality that considers the limited resources in agents. In K-armed bandit problems, despite its simpler form than the previous formalization of satisficing, RS shows better-than-optimal performances when the optimal aspiration level is given. We also show that RS shows a scalability for the number of actions, K, and an adaptability in the face of an infinite number of actions. It may be an efficient means for online learning in a complex or real environments.

Normative and descriptive rationality: from nature to artifice and back

NASA Astrophysics Data System (ADS)

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.

A resource of potential drug targets and strategic decision-making for obstructive sleep apnoea pharmacotherapy.

PubMed

Horner, Richard L; Grace, Kevin P; Wellman, Andrew

2017-07-01

There is currently no pharmacotherapy for obstructive sleep apnoea (OSA) but there is no principled a priori reason why there should not be one. This review identifies a rational decision-making strategy with the necessary logical underpinnings that any reasonable approach would be expected to navigate to develop a viable pharmacotherapy for OSA. The process first involves phenotyping an individual to quantify and characterize the critical predisposing factor(s) to their OSA pathogenesis and identify, a priori, if the patient is likely to benefit from a pharmacotherapy that targets those factors. We then identify rational strategies to manipulate those critical predisposing factor(s), and the barriers that have to be overcome for success of any OSA pharmacotherapy. A new analysis then identifies candidate drug targets to manipulate the upper airway motor circuitry for OSA pharmacotherapy. The first conclusion is that there are two general pharmacological approaches for OSA treatment that are of the most potential benefit and are practically realistic, one being fairly intuitive but the second perhaps less so. The second conclusion is that after identifying the critical physiological obstacles to OSA pharmacotherapy, there are current therapeutic targets of high interest for future development. The final analysis provides a tabulated resource of 'druggable' targets that are relatively restricted to the circuitry controlling the upper airway musculature, with these candidate targets being of high priority for screening and further study. We also emphasize that a pharmacotherapy may not cure OSA per se, but may still be a useful adjunct to improve the effectiveness of, and adherence to, other treatment mainstays. © 2017 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.

Decision Making: Rational, Nonrational, and Irrational.

ERIC Educational Resources Information Center

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…

Design and Preparation of Supported Au Catalyst with Enhanced Catalytic Activities by Rationally Positioning Au Nanoparticles on Anatase.

PubMed

Wang, Liang; Wang, Hong; Rice, Andrew E; Zhang, Wei; Li, Xiaokun; Chen, Mingshu; Meng, Xiangju; Lewis, James P; Xiao, Feng-Shou

2015-06-18

A synergistic effect between individual components is crucial for increasing the activity of metal/metal oxide catalysts. The greatest challenge is how to control the synergistic effect to obtain enhanced catalytic performance. Through density functional theory calculations of model Au/TiO2 catalysts, it is suggested that there is strong interaction between Au nanoparticles and Ti species at the edge/corner sites of anatase, which is favorable for the formation of stable oxygen vacancies. Motivated by this theoretical analysis, we have rationally prepared Au nanoparticles attached to edge/corner sites of anatase support (Au/TiO2-EC), confirmed by their HR-TEM images. As expected, this strong interaction is well characterized by Raman, UV-visible, and XPS techniques. Very interestingly, compared with conventional Au catalysts, Au/TiO2-EC exhibits superior catalytic activity in the oxidations using O2. Our approach to controlling Au nanoparticle positioning on anatase to obtain enhanced catalytic activity offers an efficient strategy for developing more novel supported metal catalysts.

Selecting the Best: Evolutionary Engineering of Chemical Production in Microbes.

PubMed

Shepelin, Denis; Hansen, Anne Sofie Lærke; Lennen, Rebecca; Luo, Hao; Herrgård, Markus J

2018-05-11

Microbial cell factories have proven to be an economical means of production for many bulk, specialty, and fine chemical products. However, we still lack both a holistic understanding of organism physiology and the ability to predictively tune enzyme activities in vivo, thus slowing down rational engineering of industrially relevant strains. An alternative concept to rational engineering is to use evolution as the driving force to select for desired changes, an approach often described as evolutionary engineering. In evolutionary engineering, in vivo selections for a desired phenotype are combined with either generation of spontaneous mutations or some form of targeted or random mutagenesis. Evolutionary engineering has been used to successfully engineer easily selectable phenotypes, such as utilization of a suboptimal nutrient source or tolerance to inhibitory substrates or products. In this review, we focus primarily on a more challenging problem-the use of evolutionary engineering for improving the production of chemicals in microbes directly. We describe recent developments in evolutionary engineering strategies, in general, and discuss, in detail, case studies where production of a chemical has been successfully achieved through evolutionary engineering by coupling production to cellular growth.

Drug Targets from Genetics: Alpha-Synuclein

PubMed Central

Danzer, Karin M.; McLean, Pamela J.

2012-01-01

One of the critical issues in Parkinson disease (PD) research is the identity of the specific toxic, pathogenic moiety. In PD, mutations in alpha-synuclein (αsyn) or multiplication of the SNCA gene encoding αsyn, result in a phenotype of cellular inclusions, cell death, and brain dysfunction. While the historical point of view has been that the macroscopic aggregates containing αsyn are the toxic species, in the last several years evidence has emerged that suggests instead that smaller soluble species - likely oligomers containing misfolded αsyn - are actually the toxic moiety and that the fibrillar inclusions may even be a cellular detoxification pathway and less harmful. If soluble misfolded species of αsyn are the toxic moieties, then cellular mechanisms that degrade misfolded αsyn would be neuroprotective and a rational target for drug development. In this review we will discuss the fundamental mechanisms underlying αsyn toxicity including oligomer formation, oxidative stress, and degradation pathways and consider rational therapeutic strategies that may have the potential to prevent or halt αsyn induced pathogenesis in PD. PMID:21838671

Rational Synthesis of Hollow Prussian Blue Analogue Through Coordination Replication and Controlled-Etching for Cs-Ion Removal.

PubMed

Xu, Jun; Bu, Fan-Xing; Guo, Yi-Fei; Zhang, Wei; Hu, Ming; Jiang, Ji-Sen

2018-05-01

Radioactive cesium pollution have received considerable attention due to the increasing risks in development of the nuclear power plants in the world. Although various functional porous materials are utilized to adsorb Cs+ ions in water, Prussian blue analogues (PBAs) are an impressive class of candidates because of their super affinity of Cs+ ions. The adsorption ability of the PBAs strongly relate to the mesostructure and interstitial sites. To design a hollow PBA with large number of interstitial sites, the traditional hollowing methods are not suitable owing to the difficulty in processing the specific PBAs with large number of interstitial sites. In this work, we empolyed a rational strategy which was to form a "metal oxide"@"PBA" core-shell structure via coordination replication at first, then utilized a mild etching to remove the metal oxide core, led to hollow PBA finally. The obtained hollow PBAs were of high crystallinity and large number of interstitial sites, showing a super adsorption performance for Cs+ ions (221.6 mg/g) within a short period (10 min).

Early rationality in action perception and production? A theoretical exposition.

PubMed

Paulus, Markus; Király, Ildikó

2013-10-01

Within recent years, the question of early rationality in action perception and production has become a topic of great interest in developmental psychology. On the one hand, studies have provided evidence for rational action perception and action imitation even in very young infants. On the other hand, scholars have recently questioned these interpretations and proposed that the ability to rationally evaluate actions is not yet in place in infancy. Others have examined the development of the ability to make rational action choices and have indicated limitations of young children's ability to act rationally. This editorial to the special issue on Early Rationality in Action Perception and Production? introduces the reader to the current debate. It elucidates the underlying theoretical assumptions that drive the debate on whether or not young children's action perception and production is rational. Finally, it summarizes the papers and their contributions to the theoretical debate. Copyright © 2013 Elsevier Inc. All rights reserved.

Tackling Energy Loss for High-Efficiency Organic Solar Cells with Integrated Multiple Strategies.

PubMed

Zuo, Lijian; Shi, Xueliang; Jo, Sae Byeok; Liu, Yun; Lin, Fracis; Jen, Alex K-Y

2018-04-01

Limited by the various inherent energy losses from multiple channels, organic solar cells show inferior device performance compared to traditional inorganic photovoltaic techniques, such as silicon and CuInGaSe. To alleviate these fundamental limitations, an integrated multiple strategy is implemented including molecular design, interfacial engineering, optical manipulation, and tandem device construction into one cell. Considering the close correlation among these loss channels, a sophisticated quantification of energy-loss reduction is tracked along with each strategy in a perspective to reach rational overall optimum. A novel nonfullerene acceptor, 6TBA, is synthesized to resolve the thermalization and V OC loss, and another small bandgap nonfullerene acceptor, 4TIC, is used in the back sub-cell to alleviate transmission loss. Tandem architecture design significantly reduces the light absorption loss, and compensates carrier dynamics and thermalization loss. Interfacial engineering further reduces energy loss from carrier dynamics in the tandem architecture. As a result of this concerted effort, a very high power conversion efficiency (13.20%) is obtained. A detailed quantitative analysis on the energy losses confirms that the improved device performance stems from these multiple strategies. The results provide a rational way to explore the ultimate device performance through molecular design and device engineering. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rational improvement of gp41-targeting HIV-1 fusion inhibitors: an innovatively designed Ile-Asp-Leu tail with alternative conformations.

PubMed

Zhu, Yun; Su, Shan; Qin, Lili; Wang, Qian; Shi, Lei; Ma, Zhenxuan; Tang, Jianchao; Jiang, Shibo; Lu, Lu; Ye, Sheng; Zhang, Rongguang

2016-09-26

Peptides derived from the C-terminal heptad repeat (CHR) of HIV gp41 have been developed as effective fusion inhibitors against HIV-1, but facing the challenges of enhancing potency and stability. Here, we report a rationally designed novel HIV-1 fusion inhibitor derived from CHR-derived peptide (Trp628~Gln653, named CP), but with an innovative Ile-Asp-Leu tail (IDL) that dramatically increased the inhibitory activity by up to 100 folds. We also determined the crystal structures of artificial fusion peptides N36- and N43-L6-CP-IDL. Although the overall structures of both fusion peptides share the canonical six-helix bundle (6-HB) configuration, their IDL tails adopt two different conformations: a one-turn helix with the N36, and a hook-like structure with the longer N43. Structural comparison showed that the hook-like IDL tail possesses a larger interaction interface with NHR than the helical one. Further molecular dynamics simulations of the two 6-HBs and isolated CP-IDL peptides suggested that hook-like form of IDL tail can be stabilized by its binding to NHR trimer. Therefore, CP-IDL has potential for further development as a new HIV fusion inhibitor, and this strategy could be widely used in developing artificial fusion inhibitors against HIV and other enveloped viruses.

The Spring of Systems Biology-Driven Breeding.

PubMed

Lavarenne, Jérémy; Guyomarc'h, Soazig; Sallaud, Christophe; Gantet, Pascal; Lucas, Mikaël

2018-05-12

Genetics and molecular biology have contributed to the development of rationalized plant breeding programs. Recent developments in both high-throughput experimental analyses of biological systems and in silico data processing offer the possibility to address the whole gene regulatory network (GRN) controlling a given trait. GRN models can be applied to identify topological features helping to shortlist potential candidate genes for breeding purposes. Time-series data sets can be used to support dynamic modelling of the network. This will enable a deeper comprehension of network behaviour and the identification of the few elements to be genetically rewired to push the system towards a modified phenotype of interest. This paves the way to design more efficient, systems biology-based breeding strategies. Copyright © 2018 Elsevier Ltd. All rights reserved.

Is cost-effective healthcare compatible with publicly financed academic medical centres?

PubMed

Chia, Whay Kuang; Toh, Han Chong

2013-01-01

Probably more than any country, Singapore has made significant investment into the biomedical enterprise as a proportion of its economy and size. This focus recently witnessed a shift towards a greater emphasis on translational and clinical development. Key to the realisation of this strategy will be Academic Medical Centres (AMCs), as a principal tool to developing and applying useful products for the market and further improving health outcomes. Here, we explore the principal value proposition of the AMC to Singapore society and its healthcare system. We question if the values inherent within academic medicine--that of inquiry, innovation, pedagogy and clinical exceptionalism--can be compatible with the seemingly paradoxical mandate of providing cost-effective or rationed healthcare.

Metabolic immune restraints: implications for anticancer vaccines.

PubMed

Mocellin, Simone

2010-01-01

Metabolic immune restraints belong to a highly complex network of molecular mechanisms underlying the failure of naturally occurring and therapeutically induced immune responses against cancer. In the light of the disappointing results yielded so far with anticancer vaccines in the clinical setting, the dissection of the cascade of molecular events leading to tumor immune escape appears the most promising way to develop more effective immunotherapeutic strategies. Here we review the significant advances recently made in the understanding of the tumor-specific metabolic features that contribute to keep malignant cells from being recognized and destroyed by immune effectors. These mechanistic insights are fostering the development of rationally designed therapeutics aimed to revert the immunosuppressive circuits and thus to enhance the effectiveness of anticancer vaccines.

The pseudo-Boolean optimization approach to form the N-version software structure

NASA Astrophysics Data System (ADS)

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

2015-10-01

The problem of developing an optimal structure of N-version software system presents a kind of very complex optimization problem. This causes the use of deterministic optimization methods inappropriate for solving the stated problem. In this view, exploiting heuristic strategies looks more rational. In the field of pseudo-Boolean optimization theory, the so called method of varied probabilities (MVP) has been developed to solve problems with a large dimensionality. Some additional modifications of MVP have been made to solve the problem of N-version systems design. Those algorithms take into account the discovered specific features of the objective function. The practical experiments have shown the advantage of using these algorithm modifications because of reducing a search space.

Open Source, Open Standards, and Health Care Information Systems

PubMed Central

2011-01-01

Recognition of the improvements in patient safety, quality of patient care, and efficiency that health care information systems have the potential to bring has led to significant investment. Globally the sale of health care information systems now represents a multibillion dollar industry. As policy makers, health care professionals, and patients, we have a responsibility to maximize the return on this investment. To this end we analyze alternative licensing and software development models, as well as the role of standards. We describe how licensing affects development. We argue for the superiority of open source licensing to promote safer, more effective health care information systems. We claim that open source licensing in health care information systems is essential to rational procurement strategy. PMID:21447469

Open source, open standards, and health care information systems.

PubMed

Reynolds, Carl J; Wyatt, Jeremy C

2011-02-17

Recognition of the improvements in patient safety, quality of patient care, and efficiency that health care information systems have the potential to bring has led to significant investment. Globally the sale of health care information systems now represents a multibillion dollar industry. As policy makers, health care professionals, and patients, we have a responsibility to maximize the return on this investment. To this end we analyze alternative licensing and software development models, as well as the role of standards. We describe how licensing affects development. We argue for the superiority of open source licensing to promote safer, more effective health care information systems. We claim that open source licensing in health care information systems is essential to rational procurement strategy.

Early Developmental Trajectories toward Concepts of Rational Numbers

ERIC Educational Resources Information Center

Kainulainen, Mikko; McMullen, Jake; Lehtinen, Erno

2017-01-01

Difficulties with rational numbers have been explained by a natural number bias, where concepts of natural numbers are inappropriately applied to rational numbers. Overcoming this difficulty may require a radical restructuring of previous knowledge. In order to capture this development, we examined third- to fifth-grade students' understanding of…

Rationality and Integration in a Family Childrearing Decision.

ERIC Educational Resources Information Center

Diana, Mark S.

This paper illuminates how concepts of rationality developed by Diesing in l962 are reflected in parents' childrearing decisions. After examining technical (TR), economic (ER), social (SR), legal (LR), and political (PR) rationalities or decision-making styles, consideration is given to integrative effects and the influence of parents' friends and…

Rational Design of Porous Conjugated Polymers and Roles of Residual Palladium for Photocatalytic Hydrogen Production.

PubMed

Li, Lianwei; Cai, Zhengxu; Wu, Qinghe; Lo, Wai-Yip; Zhang, Na; Chen, Lin X; Yu, Luping

2016-06-22

Developing highly efficient photocatalyts for water splitting is one of the grand challenges in solar energy conversion. Here, we report the rational design and synthesis of porous conjugated polymer (PCP) that photocatalytically generates hydrogen from water splitting. The design mimics natural photosynthetics systems with conjugated polymer component to harvest photons and the transition metal part to facilitate catalytic activities. A series of PCPs have been synthesized with different light harvesting chromophores and transition metal binding bipyridyl (bpy) sites. The photocatalytic activity of these bpy-containing PCPs can be greatly enhanced due to the improved light absorption, better wettability, local ordering structure, and the improved charge separation process. The PCP made of strong and fully conjugated donor chromophore DBD (M4) shows the highest hydrogen production rate at ∼33 μmol/h. The results indicate that copolymerization between a strong electron donor and weak electron acceptor into the same polymer chain is a useful strategy for developing efficient photocatalysts. This study also reveals that the residual palladium in the PCP networks plays a key role for the catalytic performance. The hydrogen generation activity of PCP photocatalyst can be further enhanced to 164 μmol/h with an apparent quantum yield of 1.8% at 350 nm by loading 2 wt % of extra platinum cocatalyst.

Structure-based approach to rationally design a chimeric protein for an effective vaccine against Group B Streptococcus infections.

PubMed

Nuccitelli, Annalisa; Cozzi, Roberta; Gourlay, Louise J; Donnarumma, Danilo; Necchi, Francesca; Norais, Nathalie; Telford, John L; Rappuoli, Rino; Bolognesi, Martino; Maione, Domenico; Grandi, Guido; Rinaudo, C Daniela

2011-06-21

Structural vaccinology is an emerging strategy for the rational design of vaccine candidates. We successfully applied structural vaccinology to design a fully synthetic protein with multivalent protection activity. In Group B Streptococcus, cell-surface pili have aroused great interest because of their direct roles in virulence and importance as protective antigens. The backbone subunit of type 2a pilus (BP-2a) is present in six immunogenically different but structurally similar variants. We determined the 3D structure of one of the variants, and experimentally demonstrated that protective antibodies specifically recognize one of the four domains that comprise the protein. We therefore constructed a synthetic protein constituted by the protective domain of each one of the six variants and showed that the chimeric protein protects mice against the challenge with all of the type 2a pilus-carrying strains. This work demonstrates the power of structural vaccinology and will facilitate the development of an optimized, broadly protective pilus-based vaccine against Group B Streptococcus by combining the uniquely generated chimeric protein with protective pilin subunits from two other previously identified pilus types. In addition, this work describes a template procedure that can be followed to develop vaccines against other bacterial pathogens.

Rational use of cognitive resources: levels of analysis between the computational and the algorithmic.

PubMed

Griffiths, Thomas L; Lieder, Falk; Goodman, Noah D

2015-04-01

Marr's levels of analysis-computational, algorithmic, and implementation-have served cognitive science well over the last 30 years. But the recent increase in the popularity of the computational level raises a new challenge: How do we begin to relate models at different levels of analysis? We propose that it is possible to define levels of analysis that lie between the computational and the algorithmic, providing a way to build a bridge between computational- and algorithmic-level models. The key idea is to push the notion of rationality, often used in defining computational-level models, deeper toward the algorithmic level. We offer a simple recipe for reverse-engineering the mind's cognitive strategies by deriving optimal algorithms for a series of increasingly more realistic abstract computational architectures, which we call "resource-rational analysis." Copyright © 2015 Cognitive Science Society, Inc.

Probability judgments of agency: rational or irrational?

PubMed

Schmidt, Thomas; Heumüller, Vera C

2010-03-01

We studied how people attribute action outcomes to their own actions under conditions of uncertainty. Participants chose between left and right keypresses to produce an action effect (a corresponding left or right light), while a computer player made a simultaneous keypress decision. In each trial, a random generator determined which of the players controlled the action effect at varying probabilities, and participants then judged which player had produced it. Participants' effect control ranged from 20% to 80%, varied blockwise, and they could use trial-by-trial feedback to optimize the accuracy of their agency judgments. Participants tended to attribute action effects to themselves (agency bias), probably reflecting a rational guessing strategy of always naming the more likely player. However, participants systematically neglected information favoring the computer player as the agent, even under conditions where this bias could only harm judgment accuracy. We conclude that agency biases have both rational and irrational components.

Social choice for one: On the rationality of intertemporal decisions.

PubMed

Paglieri, Fabio

2016-06-01

When faced with an intertemporal choice between a smaller short-term reward and a larger long-term prize, is opting for the latter always indicative of delay tolerance? And is delay tolerance always to be regarded as a manifestation of self-control, and thus as a rational solution to intertemporal dilemmas? I argue in favor of a negative answer to both questions, based on evidence collected in the delay discounting literature. This highlights the need for a nuanced understanding of rationality in intertemporal choice, to capture also situations in which waiting is not the optimal strategy. This paper suggests that such an understanding is fostered by adopting social choice theory as a promising framework to model intertemporal decision making. Some preliminary results of this approach are discussed, and its potential is compared with a much more studied formal model for intertemporal choice, i.e. game theory. Copyright © 2016 Elsevier B.V. All rights reserved.

Relationship between Student Pharmacist Decision Making Preferences and Experiential Learning.

PubMed

Williams, Charlene R; McLaughlin, Jacqueline E; Cox, Wendy C; Shepherd, Greene

2016-09-25

Objective. To determine if student pharmacists' preferences towards experiential and rational thinking are associated with performance on advanced pharmacy practice experiences (APPEs) and whether thinking style preference changes following APPEs. Methods. The Rational Experiential Inventory (REI), a validated survey of thinking style, was administered to student pharmacists before starting APPEs and re-administered after completing APPEs. APPE grades were compared to initial REI scores. Results. Rational Experiential Inventory scores remained consistent before and after APPEs. Overall, APPE grades were independent of REI scores. In a regression model, the REI experiential score was a significant negative predictor of hospital APPE grades. Conclusion. These findings suggest that overall APPE performance is independent of decision-making preference, and decision-making style does not change following immersion into APPEs. Instead of targeting teaching strategies towards a specific decision-making style, preceptors may use pedagogical approaches that promote sound clinical decision-making skills through critical thinking and reflection.

Relationship between Student Pharmacist Decision Making Preferences and Experiential Learning

PubMed Central

McLaughlin, Jacqueline E.; Cox, Wendy C.; Shepherd, Greene

2016-01-01

Objective. To determine if student pharmacists’ preferences towards experiential and rational thinking are associated with performance on advanced pharmacy practice experiences (APPEs) and whether thinking style preference changes following APPEs. Methods. The Rational Experiential Inventory (REI), a validated survey of thinking style, was administered to student pharmacists before starting APPEs and re-administered after completing APPEs. APPE grades were compared to initial REI scores. Results. Rational Experiential Inventory scores remained consistent before and after APPEs. Overall, APPE grades were independent of REI scores. In a regression model, the REI experiential score was a significant negative predictor of hospital APPE grades. Conclusion. These findings suggest that overall APPE performance is independent of decision-making preference, and decision-making style does not change following immersion into APPEs. Instead of targeting teaching strategies towards a specific decision-making style, preceptors may use pedagogical approaches that promote sound clinical decision-making skills through critical thinking and reflection. PMID:27756927

Implicit Statistical Learning in Real-World Environments Leads to Ecologically Rational Decision Making.

PubMed

Perkovic, Sonja; Orquin, Jacob Lund

2018-01-01

Ecological rationality results from matching decision strategies to appropriate environmental structures, but how does the matching happen? We propose that people learn the statistical structure of the environment through observation and use this learned structure to guide ecologically rational behavior. We tested this hypothesis in the context of organic foods. In Study 1, we found that products from healthful food categories are more likely to be organic than products from nonhealthful food categories. In Study 2, we found that consumers' perceptions of the healthfulness and prevalence of organic products in many food categories are accurate. Finally, in Study 3, we found that people perceive organic products as more healthful than nonorganic products when the statistical structure justifies this inference. Our findings suggest that people believe organic foods are more healthful than nonorganic foods and use an organic-food cue to guide their behavior because organic foods are, on average, 30% more healthful.

A Common Sense Approach to Strategy.

DTIC Science & Technology

1987-05-01

the war in his business ventures. His capacity for rational thought simply carried over into the military arena. It allowed him to effectively glean...are intelligence, situational awareness. and a decision process based on logic. Outstanding inteligence methods and exceptional intellect gave Forrest

Engineering Proteins for Thermostability with iRDP Web Server

PubMed Central

Ghanate, Avinash; Ramasamy, Sureshkumar; Suresh, C. G.

2015-01-01

Engineering protein molecules with desired structure and biological functions has been an elusive goal. Development of industrially viable proteins with improved properties such as stability, catalytic activity and altered specificity by modifying the structure of an existing protein has widely been targeted through rational protein engineering. Although a range of factors contributing to thermal stability have been identified and widely researched, the in silico implementation of these as strategies directed towards enhancement of protein stability has not yet been explored extensively. A wide range of structural analysis tools is currently available for in silico protein engineering. However these tools concentrate on only a limited number of factors or individual protein structures, resulting in cumbersome and time-consuming analysis. The iRDP web server presented here provides a unified platform comprising of iCAPS, iStability and iMutants modules. Each module addresses different facets of effective rational engineering of proteins aiming towards enhanced stability. While iCAPS aids in selection of target protein based on factors contributing to structural stability, iStability uniquely offers in silico implementation of known thermostabilization strategies in proteins for identification and stability prediction of potential stabilizing mutation sites. iMutants aims to assess mutants based on changes in local interaction network and degree of residue conservation at the mutation sites. Each module was validated using an extensively diverse dataset. The server is freely accessible at http://irdp.ncl.res.in and has no login requirements. PMID:26436543

Engineering Proteins for Thermostability with iRDP Web Server.

PubMed

Panigrahi, Priyabrata; Sule, Manas; Ghanate, Avinash; Ramasamy, Sureshkumar; Suresh, C G

2015-01-01

Engineering protein molecules with desired structure and biological functions has been an elusive goal. Development of industrially viable proteins with improved properties such as stability, catalytic activity and altered specificity by modifying the structure of an existing protein has widely been targeted through rational protein engineering. Although a range of factors contributing to thermal stability have been identified and widely researched, the in silico implementation of these as strategies directed towards enhancement of protein stability has not yet been explored extensively. A wide range of structural analysis tools is currently available for in silico protein engineering. However these tools concentrate on only a limited number of factors or individual protein structures, resulting in cumbersome and time-consuming analysis. The iRDP web server presented here provides a unified platform comprising of iCAPS, iStability and iMutants modules. Each module addresses different facets of effective rational engineering of proteins aiming towards enhanced stability. While iCAPS aids in selection of target protein based on factors contributing to structural stability, iStability uniquely offers in silico implementation of known thermostabilization strategies in proteins for identification and stability prediction of potential stabilizing mutation sites. iMutants aims to assess mutants based on changes in local interaction network and degree of residue conservation at the mutation sites. Each module was validated using an extensively diverse dataset. The server is freely accessible at http://irdp.ncl.res.in and has no login requirements.

Improving ultrasound gene transfection efficiency by controlling ultrasound excitation of microbubbles

PubMed Central

Fan, Z.; Chen, D.; Deng, C.X.

2013-01-01

Ultrasound application in the presence of microbubbles has shown great potential for non-viral gene transfection via transient disruption of cell membrane (sonoporation). However, improvement of its efficiency has largely relied on empirical approaches without consistent and translatable results. The goal of this study is to develop a rational strategy based on new results obtained using novel experimental techniques and analysis to improve sonoporation gene transfection. We conducted experiments using targeted microbubbles that were attached to cell membrane to facilitate sonoporation. We quantified the dynamic activities of microbubbles exposed to pulsed ultrasound and the resulting sonoporation outcome and identified distinct regimes of characteristic microbubble behaviors: stable cavitation, coalescence and translation, and inertial cavitation. We found that inertial cavitation generated the highest rate of membrane poration. By establishing direct correlation of ultrasound-induced bubble activities with intracellular uptake and pore size, we designed a ramped pulse exposure scheme for optimizing microbubble excitation to improve sonoporation gene transfection. We implemented a novel sonoporation gene transfection system using an aqueous two phase system (ATPS) for efficient use of reagents and high throughput operation. Using plasmid coding for the green fluorescence protein (GFP), we achieved a sonoporation transfection efficiency in rate aortic smooth muscle cells (RASMCs) of 6.9% ± 2.2% (n = 9), comparable with lipofection (7.5% ± 0.8%, n = 9). Our results reveal characteristic microbubble behaviors responsible for sonoporation and demonstrated a rational strategy to improve sonoporation gene transfection. PMID:23770009

Is poker a skill game? New insights from statistical physics

NASA Astrophysics Data System (ADS)

Javarone, Marco Alberto

2015-06-01

During last years poker has gained a lot of prestige in several countries and, besides being one of the most famous card games, it represents a modern challenge for scientists belonging to different communities, spanning from artificial intelligence to physics and from psychology to mathematics. Unlike games like chess, the task of classifying the nature of poker (i.e., as “skill game” or gambling) seems really hard and it also constitutes a current problem, whose solution has several implications. In general, gambling offers equal winning probabilities both to rational players (i.e., those that use a strategy) and to irrational ones (i.e., those without a strategy). Therefore, in order to uncover the nature of poker, a viable way is comparing performances of rational vs. irrational players during a series of challenges. Recently, a work on this topic revealed that rationality is a fundamental ingredient to succeed in poker tournaments. In this study we analyze a simple model of poker challenges by a statistical physics approach, with the aim to uncover the nature of this game. As main result we found that, under particular conditions, few irrational players can turn poker into gambling. Therefore, although rationality is a key ingredient to succeed in poker, also the format of challenges has an important role in these dynamics, as it can strongly influence the underlying nature of the game. The importance of our results lies on the related implications, as for instance in identifying the limits within which poker can be considered as a “skill game” and, as a consequence, which kind of format must be chosen to devise algorithms able to face humans.

Comprehensive assessment of the effective scope of modernization of thermal power plants to substantiate the rational structure of the generating capacities for the future until 2035

NASA Astrophysics Data System (ADS)

Veselov, F. V.; Erokhina, I. V.; Makarova, A. S.; Khorshev, A. A.

2017-03-01

The article deals with issues of technical and economic substantiation of priorities and scopes of modernizing the existing thermal power plants (TPPs) in Russia to work out long-term forecasts of the development of the industry. The current situation in the TPP modernization trends is analyzed. The updated initial figures of the capital and operation costs are presented and the obtained estimates of the comparative efficiency of various investment decisions on modernization and equipment replacement at gas-and-oil-burning and coal-fired TPPs with regard to the main zones of the national Unified Power System (UPS) of Russia are cited. The results of optimization of the generating capacity structure underlie a study of alternative TPP modernization strategies that differ in the scope of switching to new technologies, capital intensity, and energy efficiency (decrease in the average heat rate). To provide an integral economic assessment of the above strategies, the authors modified the traditional approach based on determination of the overall discounted costs of power supply (least-cost planning) supplemented with a comparison by the weighted average wholesale price of the electricity. A method for prediction of the wholesale price is proposed reasoning from the direct and dual solutions of the optimization problem. The method can be adapted to various combinations of the mechanisms of payment for the electricity and the capacity on the basis of marginal and average costs. Energy and economic analysis showed that the opposite effects of reduction in the capital investment and fuel saving change in a nonlinear way as the scope of the switch to more advanced power generation technologies at the TPPs increases. As a consequence, a strategy for modernization of the existing power plants rational with respect to total costs of the power supply and wholesale electricity prices has been formulated. The strategy combines decisions on upgrade and replacement of the equipment at the existing power plants of various types. The basic parameters of the strategy for the future until 2035 are provided.

Required Operational Capability, USMC-ROC-LOG-216.3.5 for the Ration, Cold Weather.

DTIC Science & Technology

1987-05-06

in operations or training in an arctic environment . b. Organizational Concept. The ration , cold weather will be issued in accordance with established...all services. 2 ROC-ARCTIC 7. TECHNICAL FEASIBILITY AND ENERGY/ ENVIRONMENTAL IMPACTS a. Technical Feasibility. The risk of developing the ration ...r -A1833 963 REQUIRED OPERATIONAL CAPABILITY USMC-ROC-LOG-21635 FOR 1t/1 THE RATION COLD WEATHER(U) MARINE CORPS WASHINGTON DC 86 MAY 87 USMC-ROC-LOG

Easy-going, rational, susceptible and struggling eaters: A segmentation study based on eating behaviour tendencies.

PubMed

Pentikäinen, Saara; Arvola, Anne; Karhunen, Leila; Pennanen, Kyösti

2018-01-01

Eating behaviour tendencies, emotional eating (EE), uncontrolled eating (UE) and cognitive restraint (CR), are associated with various indicators of physical and mental health. Therefore, it is important to understand these tendencies in order to design interventions to improve health. Previous research has mostly examined eating behaviour tendencies individually, without considering typical combinations of these tendencies or their manifestation in well-being and food choices. This study aimed to understand the interactive occurrence of EE, UE and CR in two independent populations. Finnish (n = 1060) and German (n = 1070) samples were segmented on the basis of their responses to a modified Three-Factor Eating Questionnaire (TFEQ-R15). Well-being, coping strategies and food consumption habits of the segments were studied. Segmentation revealed four segments: "Susceptible", "Easy-going", "Rational" and "Struggling". These segments were similar in both countries with regard to well-being, coping strategies and food choices. EE and UE co-occurred, and these tendencies were mainly responsible for differentiating the segments. Members of the "Rational" and "Easy-going" segments, who had low scores for EE and UE, tended to experience vitality and positive emotions in life, and contentment with their eating. By contrast, the "Susceptible" and "Struggling" segments, with more pronounced tendencies towards EE and UE, experienced lower levels of vitality and less frequently positive emotions, applied less adaptive coping strategies and experienced more discontent with eating. The results of the current study suggest that it is possible to identify segments, with differing eating habits, coping strategies and well-being on the basis of the eating behaviour tendencies EE, UE and CR. We discuss possible viewpoints for the design of interventions and food products to help people towards psychologically and physiologically healthier eating styles. Copyright © 2017 Elsevier Ltd. All rights reserved.

Towards a rational strategy for monitoring of microbiological quality of ambient waters

PubMed Central

Poma, Hugo Ramiro; Cacciabue, Dolores Gutiérrez; Garcé, Beatriz; Gonzo, Elio Emilio; Rajal, Verónica Beatriz

2012-01-01

Water is one of the main sources of human exposure to microbiological hazards. Although legislation establishes regulatory standards in terms of fecal indicator bacteria to assess the microbiological quality of water, these do not necessarily predict the presence of pathogens such as parasites and viruses. Better surveillance and management strategies are needed to assess the risk of pathogens waterborne transmission. We established a baseline dataset to characterize river water quality, identify changes over time, and design a rational monitoring strategy. Data from a year-long monthly monitoring campaign of the polluted Arenales River (Argentina), were analyzed to statistically correlate physicochemical and microbiological variables, the seasonal and longitudinal variation of the water quality and determine the similarity between study sites. The measured variables (sixteen) reflected the deterioration in the river quality through the city. Different viruses and parasites found did not correlate with the concentration of total and thermotolerant coliforms. There was significant seasonal variation for temperature, turbidity, conductivity, dissolved oxygen, enterococci, and norovirus. Strong correlations between some variables were found; we selected eight variables (dissolved oxygen, conductivity, turbidity, total and thermotolerant coliforms, Enterococcus, and adenovirus and Microsporidium as viral and parasitological indicators, respectively) for future monitoring. There was similarity between the monitoring locations, which were grouped into four clusters validated by cophenetic correlation and supported by discriminant analysis. This allowed us to reduce the number of sites, from eleven down to five. Sixty seven percent of the total variance and the correlation structure between variables was explained using five principal components. All these analyses led to a new long-term systematic monitoring scheme A rational monitoring strategy based on the selection of the most suitable monitoring points and of the most significant variables to measure, will result in optimal use of the limited resources available to adequately protect public and environmental health. PMID:22771467

CoPs Facing Rationalization: The Politics of Community Reproduction

ERIC Educational Resources Information Center

Kilskar, Stine Skaufel; Ingvaldsen, Jonas A.; Valle, Nina

2018-01-01

Purpose: This paper aims to explore the relationship between the contemporary forms of manufacturing rationalization and the reproduction of communities of practice (CoPs) centred on tasks and craft. Building on critical literature highlighting the tensions between CoPs and rationalization, this paper aims to develop a nuanced account of how CoPs…

Developing and Testing Rational Models of Message Design.

ERIC Educational Resources Information Center

O'Keefe, Barbara J.

1992-01-01

Responds to an article in the same issue regarding research methods for conversational cognition. Argues for a noncognitive view of rational models in communication research. Sets out an analysis of the kinds of claims made by rational models of message design. Discusses the implications of this analysis for studies of the cognitive processes…

Adolescent Identity: Rational vs. Experiential Processing, Formal Operations, and Critical Thinking Beliefs.

ERIC Educational Resources Information Center

Klaczynski, Paul A.; Fauth, James M.; Swanger, Amy

1998-01-01

The extent to which adolescents rely on rational versus experiential information processing was studied with 49 adolescents administered multiple measures of formal operations, two critical thinking questionnaires, a measure of rational processing, and a measure of ego identity status. Implications for studies of development are discussed in terms…

The Emotional and Moral Basis of Rationality

ERIC Educational Resources Information Center

Boostrom, Robert

2013-01-01

This chapter explores the basis of rationality, arguing that critical thinking tends to be taught in schools as a set of skills because of the failure to recognize that choosing to think critically depends on the prior development of stable sentiments or moral habits that nourish a rational self. Primary among these stable sentiments are the…

In-silico guided discovery of novel CCR9 antagonists

NASA Astrophysics Data System (ADS)

Zhang, Xin; Cross, Jason B.; Romero, Jan; Heifetz, Alexander; Humphries, Eric; Hall, Katie; Wu, Yuchuan; Stucka, Sabrina; Zhang, Jing; Chandonnet, Haoqun; Lippa, Blaise; Ryan, M. Dominic; Baber, J. Christian

2018-03-01

Antagonism of CCR9 is a promising mechanism for treatment of inflammatory bowel disease, including ulcerative colitis and Crohn's disease. There is limited experimental data on CCR9 and its ligands, complicating efforts to identify new small molecule antagonists. We present here results of a successful virtual screening and rational hit-to-lead campaign that led to the discovery and initial optimization of novel CCR9 antagonists. This work uses a novel data fusion strategy to integrate the output of multiple computational tools, such as 2D similarity search, shape similarity, pharmacophore searching, and molecular docking, as well as the identification and incorporation of privileged chemokine fragments. The application of various ranking strategies, which combined consensus and parallel selection methods to achieve a balance of enrichment and novelty, resulted in 198 virtual screening hits in total, with an overall hit rate of 18%. Several hits were developed into early leads through targeted synthesis and purchase of analogs.

The focused use of posters for graduate education in the complex technological nursing environment.

PubMed

Pelletier, D

1993-10-01

Posters are increasingly recognised as both a method of professional communication and a strategy for learning and assessment in nurse education. Rapid technological developments in health care and the nursing practice environment are generating specific educational needs in relation to the use of technology. There is a move to incorporate within the traditional rational technical focus a broader, more comprehensive understanding of technology, technological equipment and procedures. Technological innovations are an ideal subject matter for poster presentations at the graduate level particularly as broader dimensions such as the impetus for introduction, the research base, the evaluation strategy and the cost can be incorporated. Each poster can become a teaching focus for a student presentation to classmates or other professional forums in order to catalyse discussions of these wider dimensions. A description of the use of posters for these purposes with examples and comments by participants is included.

Ultralong room temperature phosphorescence from amorphous organic materials toward confidential information encryption and decryption.

PubMed

Su, Yan; Phua, Soo Zeng Fiona; Li, Youbing; Zhou, Xianju; Jana, Deblin; Liu, Guofeng; Lim, Wei Qi; Ong, Wee Kong; Yang, Chaolong; Zhao, Yanli

2018-05-01

Ultralong room temperature phosphorescence (URTP) emitted from pure amorphous organic molecules is very rare. Although a few crystalline organic molecules could realize URTP with long lifetimes (>100 ms), practical applications of these crystalline organic phosphors are still challenging because the formation and maintenance of high-quality crystals are very difficult and complicated. Herein, we present a rational design for minimizing the vibrational dissipation of pure amorphous organic molecules to achieve URTP. By using this strategy, a series of URTP films with long lifetimes and high phosphorescent quantum yields (up to 0.75 s and 11.23%, respectively) were obtained from amorphous organic phosphors without visible fluorescence and phosphorescence under ambient conditions. On the basis of the unique features of URTP films, a new green screen printing technology without using any ink was developed toward confidential information encryption and decryption. This work presents a breakthrough strategy in applying amorphous organic materials for URTP.

Molecular Imaging of Apoptosis: From Micro to Macro

PubMed Central

Zeng, Wenbin; Wang, Xiaobo; Xu, Pengfei; Liu, Gang; Eden, Henry S.; Chen, Xiaoyuan

2015-01-01

Apoptosis, or programmed cell death, is involved in numerous human conditions including neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer, and is often confused with other types of cell death. Therefore strategies that enable visualized detection of apoptosis would be of enormous benefit in the clinic for diagnosis, patient management, and development of new therapies. In recent years, improved understanding of the apoptotic machinery and progress in imaging modalities have provided opportunities for researchers to formulate microscopic and macroscopic imaging strategies based on well-defined molecular markers and/or physiological features. Correspondingly, a large collection of apoptosis imaging probes and approaches have been documented in preclinical and clinical studies. In this review, we mainly discuss microscopic imaging assays and macroscopic imaging probes, ranging in complexity from simple attachments of reporter moieties to proteins that interact with apoptotic biomarkers, to rationally designed probes that target biochemical changes. Their clinical translation will also be our focus. PMID:25825597

Conversion of red fluorescent protein into a bright blue probe.

PubMed

Subach, Oksana M; Gundorov, Illia S; Yoshimura, Masami; Subach, Fedor V; Zhang, Jinghang; Grüenwald, David; Souslova, Ekaterina A; Chudakov, Dmitriy M; Verkhusha, Vladislav V

2008-10-20

We used a red chromophore formation pathway, in which the anionic red chromophore is formed from the neutral blue intermediate, to suggest a rational design strategy to develop blue fluorescent proteins with a tyrosine-based chromophore. The strategy was applied to red fluorescent proteins of the different genetic backgrounds, such as TagRFP, mCherry, HcRed1, M355NA, and mKeima, which all were converted into blue probes. Further improvement of the blue variant of TagRFP by random mutagenesis resulted in an enhanced monomeric protein, mTagBFP, characterized by the substantially higher brightness, the faster chromophore maturation, and the higher pH stability than blue fluorescent proteins with a histidine in the chromophore. The detailed biochemical and photochemical analysis indicates that mTagBFP is the true monomeric protein tag for multicolor and lifetime imaging, as well as the outstanding donor for green fluorescent proteins in Förster resonance energy transfer applications.

Advances and prospects of Bacillus subtilis cellular factories: From rational design to industrial applications.

PubMed

Gu, Yang; Xu, Xianhao; Wu, Yaokang; Niu, Tengfei; Liu, Yanfeng; Li, Jianghua; Du, Guocheng; Liu, Long

2018-05-15

Bacillus subtilis is the most characterized gram-positive bacterium that has significant attributes, such as growing well on cheap carbon sources, possessing clear inherited backgrounds, having mature genetic manipulation methods, and exhibiting robustness in large-scale fermentations. Till date, B. subtilis has been identified as attractive hosts for the production of recombinant proteins and chemicals. By applying various systems and synthetic biology tools, the productivity features of B. subtilis can be thoroughly analyzed and further optimized via metabolic engineering. In the present review, we discussed why B. subtilis is the primary organisms used for metabolic engineering and industrial applications. Additionally, we summarized the recent advances in systems and synthetic biology, engineering strategies for improving cellular performances, and metabolic engineering applications of B. subtilis. In particular, we proposed emerging opportunities and essential strategies to enable the successful development of B. subtilis as microbial cell factories. Copyright © 2018. Published by Elsevier Inc.

A cognitive prosthesis for complex decision-making.

PubMed

Tremblay, Sébastien; Gagnon, Jean-François; Lafond, Daniel; Hodgetts, Helen M; Doiron, Maxime; Jeuniaux, Patrick P J M H

2017-01-01

While simple heuristics can be ecologically rational and effective in naturalistic decision making contexts, complex situations require analytical decision making strategies, hypothesis-testing and learning. Sub-optimal decision strategies - using simplified as opposed to analytic decision rules - have been reported in domains such as healthcare, military operational planning, and government policy making. We investigate the potential of a computational toolkit called "IMAGE" to improve decision-making by developing structural knowledge and increasing understanding of complex situations. IMAGE is tested within the context of a complex military convoy management task through (a) interactive simulations, and (b) visualization and knowledge representation capabilities. We assess the usefulness of two versions of IMAGE (desktop and immersive) compared to a baseline. Results suggest that the prosthesis helped analysts in making better decisions, but failed to increase their structural knowledge about the situation once the cognitive prosthesis is removed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Disrupting beta-amyloid aggregation for Alzheimer disease treatment.

PubMed

Estrada, L D; Soto, C

2007-01-01

Alzheimer's disease is a devastating degenerative disorder for which there is no cure or effective treatment. Although the etiology of Alzheimer's disease is not fully understood, compelling evidence indicates that deposition of aggregates composed by a misfolded form of the amyloid beta peptide (Abeta) is the central event in the disease pathogenesis. Therefore, an attractive therapeutic strategy is to prevent or reverse Abeta misfolding and aggregation. Diverse strategies have been described to identify inhibitors of this process, including screening of libraries of small molecules chemical compounds, rational design of synthetic peptides, assessment of natural Abeta-binding proteins and stimulation of the immune system by vaccination. In this article we describe these different approaches, their principles and their potential strengths and weaknesses. Overall the available data suggest that the development of drugs to interfere with Abeta misfolding and aggregation is a feasible target that hold great promise for the treatment of Alzheimer's disease.

Engineering the architectural diversity of heterogeneous metallic nanocrystals.

PubMed

Yu, Yue; Zhang, Qingbo; Xie, Jianping; Lee, Jim Yang

2013-01-01

Similar to molecular engineering where structural diversity is used to create more property variations for application explorations, the architectural engineering of heterogeneous metallic nanocrystals (HMNCs) can likewise increase the versatility of metallic nanocrystals (NCs). Here we present a synthesis strategy capable of engineering the architectural diversity of HMNCs through rational and independent programming of every architecture-determining element, that is, the shape and size of the component NCs and their spatial arrangement. The strategy is based on the galvanic replacement reaction of a self-sustaining layer formed by underpotential deposition on a polyhedral NC. The selective deposition of satellite NCs on specific site of the central NC is realized by creating a geometry-dependent heterogeneous electron distribution. This site-selective deposition approach is applicable to central NCs in various polyhedral shapes and sizes. The satellite NCs can further develop their own shape and size through crystal growth kinetics control.

Chemical synthesis of the tetrasaccharide repeating unit of the O-polysaccharide isolated from Azospirillum brasilense SR80.

PubMed

Sarkar, Vikramjit; Mukhopadhyay, Balaram

2015-04-10

A linear strategy has been developed for the synthesis of the tetrasaccharide repeating unit of the O-polysaccharide from Azospirillum brasilense SR80. Stepwise glycosylation of the rationally protected thioglycoside donors activated by NIS in the presence of La(OTf)3 furnished the target tetrasaccharide. The glycosylation reactions resulted in the formation of the desired linkage with absolute stereoselectivity and afforded the required derivatives in good to excellent yields. The phthalimido group has been used as the precursor of the desired acetamido group to meet the requirement of 1,2-trans glycosidic linkage. Copyright © 2015 Elsevier Ltd. All rights reserved.

Porphyrin-Based Nanostructures for Photocatalytic Applications

PubMed Central

Chen, Yingzhi; Li, Aoxiang; Huang, Zheng-Hong; Wang, Lu-Ning; Kang, Feiyu

2016-01-01

Well-defined organic nanostructures with controllable size and morphology are increasingly exploited in optoelectronic devices. As promising building blocks, porphyrins have demonstrated great potentials in visible-light photocatalytic applications, because of their electrical, optical and catalytic properties. From this perspective, we have summarized the recent significant advances on the design and photocatalytic applications of porphyrin-based nanostructures. The rational strategies, such as texture or crystal modification and interfacial heterostructuring, are described. The applications of the porphyrin-based nanostructures in photocatalytic pollutant degradation and hydrogen evolution are presented. Finally, the ongoing challenges and opportunities for the future development of porphyrin nanostructures in high-quality nanodevices are also proposed. PMID:28344308

Porous Hydrogen-Bonded Organic Frameworks.

PubMed

Han, Yi-Fei; Yuan, Ying-Xue; Wang, Hong-Bo

2017-02-13

Ordered porous solid-state architectures constructed via non-covalent supramolecular self-assembly have attracted increasing interest due to their unique advantages and potential applications. Porous metal-coordination organic frameworks (MOFs) are generated by the assembly of metal coordination centers and organic linkers. Compared to MOFs, porous hydrogen-bonded organic frameworks (HOFs) are readily purified and recovered via simple recrystallization. However, due to lacking of sufficiently ability to orientate self-aggregation of building motifs in predictable manners, rational design and preparation of porous HOFs are still challenging. Herein, we summarize recent developments about porous HOFs and attempt to gain deeper insights into the design strategies of basic building motifs.

When is rational to order a diagnostic test, or prescribe treatment: the threshold model as an explanation of practice variation.

PubMed

Djulbegovic, Benjamin; van den Ende, Jef; Hamm, Robert M; Mayrhofer, Thomas; Hozo, Iztok; Pauker, Stephen G

2015-05-01

The threshold model represents an important advance in the field of medical decision-making. It is a linchpin between evidence (which exists on the continuum of credibility) and decision-making (which is a categorical exercise - we decide to act or not act). The threshold concept is closely related to the question of rational decision-making. When should the physician act, that is order a diagnostic test, or prescribe treatment? The threshold model embodies the decision theoretic rationality that says the most rational decision is to prescribe treatment when the expected treatment benefit outweighs its expected harms. However, the well-documented large variation in the way physicians order diagnostic tests or decide to administer treatments is consistent with a notion that physicians' individual action thresholds vary. We present a narrative review summarizing the existing literature on physicians' use of a threshold strategy for decision-making. We found that the observed variation in decision action thresholds is partially due to the way people integrate benefits and harms. That is, explanation of variation in clinical practice can be reduced to a consideration of thresholds. Limited evidence suggests that non-expected utility threshold (non-EUT) models, such as regret-based and dual-processing models, may explain current medical practice better. However, inclusion of costs and recognition of risk attitudes towards uncertain treatment effects and comorbidities may improve the explanatory and predictive value of the EUT-based threshold models. The decision when to act is closely related to the question of rational choice. We conclude that the medical community has not yet fully defined criteria for rational clinical decision-making. The traditional notion of rationality rooted in EUT may need to be supplemented by reflective rationality, which strives to integrate all aspects of medical practice - medical, humanistic and socio-economic - within a coherent reasoning system. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

Expanding pH screening space using multiple droplets with secondary buffers for protein crystallization

NASA Astrophysics Data System (ADS)

Zhang, Chen-Yan; Dong, Chen; Lu, Xiao-Li; Wang, Bei; He, Tian-Yuan; Yang, Rui-Zeng; Lin, Hua-Long; Yang, Xue-Zhou; Yin, Da-Chuan

2017-04-01

We have proposed a rational strategy for selecting a suitable pH of protein solution based on protein biochemical properties. However, it is difficult to use this strategy for biochemical properties unknown proteins. In this paper, a simpler and faster pH buffer strategy was proposed. An additional pH-controlling buffer was added to crystallization droplet mixed with protein solution and commercial crystallization reagents to adjust its pH. The results revealed that protein crystallization success rates were enhanced by this strategy due to expansion of the pH screening space, which was closely related with protein solubility. Thus, the possibility of reaching supersaturation was increased by using this strategy.

Cooperation in spatial evolutionary games with historical payoffs

NASA Astrophysics Data System (ADS)

Wang, Xu-Wen; Nie, Sen; Jiang, Luo-Luo; Wang, Bing-Hong; Chen, Shi-Ming

2016-08-01

The most common of strategy adoption in evolutionary games relies on players' payoffs of the last round. While a rational player usually fixes the coming strategy by comprehensively considering certain amount of payoff information within its memory length. Here, we explore several measures of historical payoffs in getting the weighted average payoff. Then, player sets the strategy by comparing the weighted average payoff of neighbour's and itself. We show that, cooperators can resist the invasion by referring to the most payoff information, when strategy and measure coevolve. In contrast, strategy adoption of defectors only relies on the nearest one round. Especially, our results suggest that, excessive attention of past payoffs is not favorable to spread cooperative behaviors.

Strategies for rational utilization of bituminous coal deposits in the German Federal Republic

NASA Astrophysics Data System (ADS)

Erasmus, F. C.; Lenhartz, R.

1980-09-01

The status and economic conditions for coal mining in the GFR are examined, and the production of the individual coal regions is reviewed. Exploratory work, conducted in the light of inevitable production increases in the future, is noted. Some changes in the present coal production and utilization strategies which may be needed to meet future requirements and at the same time optimize the mining procedures are discussed.

Decision Making Styles and Progress in Occupational Decision Making.

ERIC Educational Resources Information Center

Phillips, Susan D.; And Others

1984-01-01

Examined the role of rational, intuitive, and dependent decisional strategies in facilitating decisions about postcollege occupation among college students (N=71). Results indicated that the use of a dependent decision-making style was the single most powerful predictor of progress. (LLL)

Toward an Information-Processing Theory of Client Change in Counseling.

ERIC Educational Resources Information Center

Martin, Jack

1985-01-01

Information-processing models of client-centered and rational-emotive counseling are constructed that relate counseling skills and strategies employed in these approaches to hypothesized client cognitive changes. An integrated view of client cognitive change in counseling also is presented. (Author/BL)

A comparison of individual cow versus group concentrate allocation strategies on dry matter intake, milk production, tissue changes, and fertility of Holstein-Friesian cows offered a grass silage diet.

PubMed

Little, M W; O'Connell, N E; Ferris, C P

2016-06-01

A diverse range of concentrate allocation strategies are adopted on dairy farms. The objectives of this study were to examine the effects on cow performance [dry matter (DM) intake (DMI), milk yield and composition, body tissue changes, and fertility] of adopting 2 contrasting concentrate allocation strategies over the first 140 d of lactation. Seventy-seven Holstein-Friesian dairy cows were allocated to 1 of 2 concentrate allocation strategies at calving, namely group or individual cow. Cows on the group strategy were offered a mixed ration comprising grass silage and concentrates in a 50:50 ratio on a DM basis. Cows on the individual cow strategy were offered a basal mixed ration comprising grass silage and concentrates (the latter included in the mix to achieve a mean intake of 6kg/cow per day), which was formulated to meet the cow's energy requirements for maintenance plus 24kg of milk/cow per day. Additional concentrates were offered via an out-of-parlor feeding system, with the amount offered adjusted weekly based on each individual cow's milk yield during the previous week. In addition, all cows received a small quantity of straw in the mixed ration part of the diet (approximately 0.3kg/cow per day), plus 0.5kg of concentrate twice daily in the milking parlor. Mean concentrate intakes over the study period were similar with each of the 2 allocation strategies (11.5 and 11.7kg of DM/cow per day for group and individual cow, respectively), although the pattern of intake with each treatment differed over time. Concentrate allocation strategy had no effect on either milk yield (39.3 and 38.0kg/d for group and individual cow, respectively), milk composition, or milk constituent yield. The milk yield response curves with each treatment were largely aligned with the concentrate DMI curves. Cows on the individual cow treatment had a greater range of concentrate DMI and milk yields than those on the group treatment. With the exception of a tendency for cows on the individual cow treatment to lose more body weight to nadir than cows on the group treatment, concentrate allocation strategy had little effect on either body weight or body condition score over the experimental period. Cows on the individual cow treatment had a higher pregnancy rate to first and second service and tended to have a higher 100-d in calf rate than cows on the group treatment. This study demonstrates that concentrate allocation strategy had little effect on overall production performance. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Development of a database system for operational use in the selection of titanium alloys

NASA Astrophysics Data System (ADS)

Han, Yuan-Fei; Zeng, Wei-Dong; Sun, Yu; Zhao, Yong-Qing

2011-08-01

The selection of titanium alloys has become a complex decision-making task due to the growing number of creation and utilization for titanium alloys, with each having its own characteristics, advantages, and limitations. In choosing the most appropriate titanium alloys, it is very essential to offer a reasonable and intelligent service for technical engineers. One possible solution of this problem is to develop a database system (DS) to help retrieve rational proposals from different databases and information sources and analyze them to provide useful and explicit information. For this purpose, a design strategy of the fuzzy set theory is proposed, and a distributed database system is developed. Through ranking of the candidate titanium alloys, the most suitable material is determined. It is found that the selection results are in good agreement with the practical situation.

Emotional and rational disease acceptance in patients with depression and alcohol addiction.

PubMed

Büssing, Arndt; Matthiessen, Peter F; Mundle, Götz

2008-01-21

The concept of a rational respectively emotional acceptance of disease is highly valued in the treatment of patients with depression or addiction. Due to the importance of this concept for the long-term course of disease, there is a strong interest to develop a tool to identify the levels and factors of acceptance. We thus intended to test an instrument designed to assess the level of positive psychological wellbeing and coping, particularly emotional disease acceptance and life satisfaction In an anonymous cross-sectional survey enrolling 115 patients (51% female, 49% male; mean age 47.6 +/- 10.0 years) with depression and/or alcohol addiction, the ERDA questionnaire was tested. Factor analysis of the 29-item construct (Cronbach's alpha = 0.933) revealed a 4-factor solution, which explained 59.4% of variance: (1) Positive Life Construction, Contentedness and Well-Being; (2) Conscious Dealing with Illness; (3) Rejection of an Irrational Dealing with Disease; (4) Disease Acceptance. Two factors could be ascribed to a rational, and two to an emotional acceptance. All factors correlated negatively with Depression and Escape, while several aspects of Life Satisfaction" (i.e. myself, overall life, where I live, and future prospects) correlated positively. The highest factor scores were found for the rational acceptance styles (i.e. Conscious Dealing with Illness; Disease Acceptance). Emotional acceptance styles were not valued in a state of depression. Escape from illness was the strongest predictor for several acceptance aspects, while life satisfaction was the most relevant predictor for "Positive Life Construction, Contentedness and Well-Being". The ERDA questionnaire was found to be a reliable and valid assessment of disease acceptance strategies in patients with depressive disorders and drug abuses. The results indicate the preferential use of rational acceptance styles even in depression. Disease acceptance should not be regarded as a coping style with an attitude of fatalistic resignation, but as a complex and active process of dealing with a chronic disease. One may assume that an emotional acceptance of disease will result in a therapeutic coping process associated with higher level of life satisfaction and overall quality of life.

Alternative feeding strategies and potential disease transmission in Wisconsin white-tailed deer

USGS Publications Warehouse

Thompson, A.K.; Samuel, M.D.; VanDeelen, T.R.

2008-01-01

We conducted experimental feeding using 3 feeding methods (pile, spread, trough) and 2 quantities (rationed, ad libitum) of shelled corn to compare deer activity and behavior with control sites and evaluate potential direct and indirect transmission of infectious disease in white-tailed deer (Odocoileus virginianus) in central Wisconsin, USA. Deer use was higher at 2 of the feeding sites than at natural feeding areas (P ??? 0.02). Deer spent a higher proportion of time (P < 0.01) feeding at pile (49%) and spread (61%) treatments than at natural feeding areas (36%). We found higher deer use for rationed than ad libitum feeding quantities and feeding intensity was greatest at rationed piles and lowest at ad libitum spreads. We also observed closer pairwise distances (???0.3 m) among deer when corn was provided in a trough relative to spread (P=0.03). Supplemental feeding poses risks for both direct and indirect disease transmission due to higher deer concentration and more intensive use relative to control areas. Concentrated feeding and contact among deer at feeding sites can also increase risk for disease transmission. Our results indicated that restrictions on feeding quantity would not mitigate the potential for disease transmission None of the feeding strategies we evaluated substantially reduced the potential risk for disease transmission and banning supplemental feeding to reduce transmission is warranted.

[Influenza A from the rational choice theory: proposals for decision making in prevention policies].

PubMed

Peña, Francisco Garrido; Fernández, Luís Andrés López; García, Eugenia Gil

2009-01-01

This article is a reflection on the social uncertainty caused by Influenza A and on the consequences that it can have on decision making in health promotion policies. We use concepts and metaphors of the Rational Choice Theory, among them, the "in gratitude effect" or the "distrust effect", as we analyse how these can become obstacles for the efficiency of prevention policies. Then, we focus on the information asymmetry of the principal-agent relationship, and we propose measures to diminish the "moral risk" that they cause. We finish by advancing some proposals for designing lines and strategies of action in health promotion policies.

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

PubMed

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

2013-01-01

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

Fostering ethical willingness: integrating emotional and contextual awareness with rational analysis.

PubMed

Betan, E J; Stanton, A L

1999-06-01

Ethical dilemmas are inherently challenging. By definition, clinicians decide between conflicting principles of welfare and naturally confront competing pulls and inclinations. This investigation of students' responses to an ethical scenario highlights how emotions and concerns can interfere with willingness to implement ethical knowledge. Clear-cut rules are the exception in psychotherapy, and clinicians must judge ethical issues on the basis of the unique context of each case. As such, subjectivity and emotional involvement are essential tools for determining ethical action, but they must be integrated with rational analysis. Strategies for attending to influential emotions and contextual factors in order to mobilize ethical commitment are described.

A 2020 vision for vaccines against HIV, tuberculosis and malaria.

PubMed

Rappuoli, Rino; Aderem, Alan

2011-05-26

Acquired immune deficiency syndrome (AIDS), malaria and tuberculosis collectively cause more than five million deaths per year, but have nonetheless eluded conventional vaccine development; for this reason they represent one of the major global public health challenges as we enter the second decade of the twenty-first century. Recent trials have provided evidence that it is possible to develop vaccines that can prevent infection by human immunodeficiency virus (HIV) and malaria. Furthermore, advances in vaccinology, including novel adjuvants, prime-boost regimes and strategies for intracellular antigen presentation, have led to progress in developing a vaccine against tuberculosis. Here we discuss these advances and suggest that new tools such as systems biology and structure-based antigen design will lead to a deeper understanding of mechanisms of protection which, in turn, will lead to rational vaccine development. We also argue that new and innovative approaches to clinical trials will accelerate the availability of these vaccines.

[Continuity and non-continuity from child- to adulthood in psychiatric clinical studies].

PubMed

Kuwabara, Hitoshi; Kawakubo, Yuki; Kano, Yukiko

2014-01-01

It is difficult to conceive of the development of the brain as a single process, especially when we think about continuity and non-continuity from child- to adulthood. Non-continuity may be present when the brain is developing normally or consistently, or during aging, and development may vary across behavioral, structural, functional, and regional units. Clinical studies that consider the developmental process of change as natural and expected may better incorporate the potential variety and non-continuity than clinical studies that do not consider the process of change. It is likely that these complications are exacerbated because the timing of changes appears to vary across units. If we can identify the critical points of plasticity, temporally appropriate interventions can be developed. A focus on the developmental process of changes in the brain may lead to more rational and effective intervention strategies.

Drought Water Rationing Necessitates an Equitable and Multidimensional Approach: Evidence from California

NASA Astrophysics Data System (ADS)

Ponce de Leon Barido, D.; Fildier, B.; Cucchi, K.

2016-12-01

Since 2011 many areas across California have experienced their driest years on record, with conditions barely improving since then. Reservoirs and snowpack water content have recorded some of the lowest measurements ever, with users (individuals, towns and cities) using groundwater to buffer the potentially devastating effects of the drought. Among other strategies, rationing has been one of they key interventions that the state has adopted to better manage its water resources. April 1st 2015 marked the first day in California's history when mandatory water reductions were instated statewide. By executive order, Governor Brown directed the State Water Resources Control Board to impose a 25% reduction on California's 400 local water supply agencies, which serve 90% of California residents. Since then, local agencies have been responsible for allocating restrictions to reduce water consumption and monitor compliance. A variety of research organizations and media outlets have begun exploring the equity considerations of the drought, but their analyses are often one-dimensional (water consumption per capita). Here we explore the multi-dimensional dynamics of rationing and drought in California using Census and California Water Resources Board data for over 300 communities in the state. We use data mining, parallel coordinates, and a nearest neighbors clustering algorithm to explore relationships between rationing and community spatial distribution, weather, drought related climate variables, economic sector employment, race, localized income inequality, household size, and income. The data suggests that there are nine distinct rationing groups across the state, that rationing was performed without taking into account the localized effects of the drought (hard hit communities rationing as much as less affected communities), that severely drought affected low-income communities (using SPI and SPEI 3 year indices) were asked to ration as much (and sometimes more) than less drought affected high-income communities, and that even after tight conservation standards on large consumers, high-income communities still consumed 30% more water per capita than low-income communities. We conclude with a suggested framework for how more equitable rationing could be implemented in the future.

Rational Design, Development, and Stability Assessment of a Macrocyclic Four-Hydroxamate-Bearing Bifunctional Chelating Agent for 89 Zr.

PubMed

Seibold, Uwe; Wängler, Björn; Wängler, Carmen

2017-09-21

Zirconium-89 is a positron-emitting radionuclide of high interest for medical imaging applications with positron emission tomography (PET). For the introduction of this radiometal into biologically active targeting vectors, the chelating agent desferrioxamine B (DFO) is commonly applied. However, DFO is known to form 89 Zr complexes of limited in vivo stability. Herein we describe the rational design and chemical development of a new macrocyclic four-hydroxamate-bearing chelating agent-1,10,19,28-tetrahydroxy-1,5,10,14,19,23,28,32-octaazacyclohexatriacontan-2,6,11,15,20,24,29,33-octaone (CTH36)-for the stable complexation of Zr 4+ . For this purpose, we first performed computational studies to determine the optimal chelator geometry before we developed different synthesis pathways toward the target structures. The best results were obtained using an efficient solution-phase-based synthesis strategy toward the target chelating agent. To enable efficient and chemoselective conjugation to biomolecules, a tetrazine-modified variant of CTH36 was also developed. The excellent conjugation characteristics of the so-functionalized chelator were demonstrated on the example of the model peptide TCO-c(RGDfK). We determined the optimal 89 Zr radiolabeling parameters for CTH36 as well as its bioconjugate, and found that 89 Zr radiolabeling proceeds efficiently under very mild reaction conditions. Finally, we performed comparative complex stability tests for 89 Zr-CHT36-c(RGDfK) and 89 Zr-DFO-c(RGDfK), showing improved complex stability for the newly developed chelator CTH36. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Revising Rationality: The Use of "Nudge" Approaches in Neoliberal Education Policy

ERIC Educational Resources Information Center

Bradbury, Alice; McGimpsey, Ian; Santori, Diego

2013-01-01

This article argues that the concept of rationality is undergoing significant revision in UK education policy-making, influenced by developments in several academic fields. This article focuses on the take up of behavioural economics in policy as one aspect of this revision of the concept of rationality, discussing how this has happened and its…

Developing Essential Understanding of Rational Numbers for Teaching Mathematics in Grades 3-5. Essential Understandings

ERIC Educational Resources Information Center

Clarke, Carne; Fisher, William; Marks, Rick; Ross, Sharon; Zbiek, Rose Mary

2010-01-01

This book focuses on essential knowledge for teachers about rational numbers. It is organized around four big ideas, supported by multiple smaller, interconnected ideas--essential understandings. Taking teachers beyond a simple introduction to rational numbers, the book will broaden and deepen their mathematical understanding of one of the most…

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

ERIC Educational Resources Information Center

Patton, Patricia Lucey

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

Aging and loss decision making: increased risk aversion and decreased use of maximizing information, with correlated rationality and value maximization.

PubMed

Kurnianingsih, Yoanna A; Sim, Sam K Y; Chee, Michael W L; Mullette-Gillman, O'Dhaniel A

2015-01-01

We investigated how adult aging specifically alters economic decision-making, focusing on examining alterations in uncertainty preferences (willingness to gamble) and choice strategies (what gamble information influences choices) within both the gains and losses domains. Within each domain, participants chose between certain monetary outcomes and gambles with uncertain outcomes. We examined preferences by quantifying how uncertainty modulates choice behavior as if altering the subjective valuation of gambles. We explored age-related preferences for two types of uncertainty, risk, and ambiguity. Additionally, we explored how aging may alter what information participants utilize to make their choices by comparing the relative utilization of maximizing and satisficing information types through a choice strategy metric. Maximizing information was the ratio of the expected value of the two options, while satisficing information was the probability of winning. We found age-related alterations of economic preferences within the losses domain, but no alterations within the gains domain. Older adults (OA; 61-80 years old) were significantly more uncertainty averse for both risky and ambiguous choices. OA also exhibited choice strategies with decreased use of maximizing information. Within OA, we found a significant correlation between risk preferences and choice strategy. This linkage between preferences and strategy appears to derive from a convergence to risk neutrality driven by greater use of the effortful maximizing strategy. As utility maximization and value maximization intersect at risk neutrality, this result suggests that OA are exhibiting a relationship between enhanced rationality and enhanced value maximization. While there was variability in economic decision-making measures within OA, these individual differences were unrelated to variability within examined measures of cognitive ability. Our results demonstrate that aging alters economic decision-making for losses through changes in both individual preferences and the strategies individuals employ.

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-05-01

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

The role of cognitive style in the stress and coping of black South African adolescents.

PubMed

van Rooyen, Melinda; Naude, Luzelle; Nel, Lindi; Esterhuyse, Karel

2014-12-01

Although stress is a common phenomenon in all phases of life, it can be said that adolescence is a particularly stressful life stage. In South Africa, black adolescents are faced with many stressors and challenges which are placing demands on their emotional and cognitive resources. The aim of this study was to determine whether black South African adolescents with different cognitive styles (i.e. rational or experiential) differ in their levels of stress and coping. Furthermore, the common stressors that black adolescents experience and the coping styles predominantly used by black adolescents could be determined. One hundred and eighty-seven participants (88 males and 99 females) completed the Rational Experiential, the Coping Reponses and the Adolescent Stress Inventory. Adolescents operating from an experiential cognitive style experienced more stress regarding school performance, school attendance, financial pressure and emerging adult responsibility than adolescents operating from a rational cognitive style. Adolescents employing a rational style sought more alternative rewards as a coping strategy, whereas adolescents employing an experiential style relied more on emotional discharge. The findings of this study concur with previous research, but provide a unique perspective on adolescents' stress and coping in this South African context.

Deep Rationality: The Evolutionary Economics of Decision Making

PubMed Central

Kenrick, Douglas T.; Griskevicius, Vladas; Sundie, Jill M.; Li, Norman P.; Li, Yexin Jessica; Neuberg, Steven L.

2009-01-01

What is a “rational” decision? Economists traditionally viewed rationality as maximizing expected satisfaction. This view has been useful in modeling basic microeconomic concepts, but falls short in accounting for many everyday human decisions. It leaves unanswered why some things reliably make people more satisfied than others, and why people frequently act to make others happy at a cost to themselves. Drawing on an evolutionary perspective, we propose that people make decisions according to a set of principles that may not appear to make sense at the superficial level, but that demonstrate rationality at a deeper evolutionary level. By this, we mean that people use adaptive domain-specific decision-rules that, on average, would have resulted in fitness benefits. Using this framework, we re-examine several economic principles. We suggest that traditional psychological functions governing risk aversion, discounting of future benefits, and budget allocations to multiple goods, for example, vary in predictable ways as a function of the underlying motive of the decision-maker and individual differences linked to evolved life-history strategies. A deep rationality framework not only helps explain why people make the decisions they do, but also inspires multiple directions for future research. PMID:20686634

When is diagnostic testing inappropriate or irrational? Acceptable regret approach.

PubMed

Hozo, Iztok; Djulbegovic, Benjamin

2008-01-01

The authors provide a new model within the framework of theories of bounded rationality for the observed physicians' behavior that their ordering of diagnostic tests may not be rational. Contrary to the prevailing thinking, the authors find that physicians do not act irrationally or inappropriately when they order diagnostic tests in usual clinical practice. When acceptable regret (i.e., regret that a decision maker finds tolerable upon making a wrong decision) is taken into account, the authors show that physicians tend to order diagnostic tests at a higher level of pretest probability of disease than predicted by expected utility theory. They also show why physicians tend to overtest when regret about erroneous decisions is extremely small. Finally, they explain variations in the practice of medicine. They demonstrate that in the same clinical situation, different decision makers might have different acceptable regret thresholds for withholding treatment, for ordering a diagnostic test, or for administering treatment. This in turn means that for some decision makers, the most rational strategy is to do nothing, whereas for others, it may be to order a diagnostic test, and still for others, choosing treatment may be the most rational course of action.

Characterizing Solution Concepts in Games Using Knowledge Based Programs

DTIC Science & Technology

2007-01-01

rationalizable strategies [ Bernheim , 1984; Pearce, 1984]. Using a characterization due to Halpern [2006], we can show that if their prior is described...knowledge of rationality. Games and Economic Behavior, 8:6–19, 1995. [ Bernheim , 1984] B. D. Bernheim . Rationalizable strategic behavior. Econometrica, 52

Pure National Security Strategy

DTIC Science & Technology

2011-06-01

British Major General J. F. C. Fuller concludes through reading French positivist Comte that the only way to construct understanding rationally is...Affairs, July/ August 1999, Vol. 78, No. 4. Buffalo, New York: William S. Hein & Co., Inc. Nye, Joseph S. The Paradox of American Power: Why the

Give Deterrence a Chance: A Strategy Against Al Qaeda

DTIC Science & Technology

2007-03-28

Al Qaeda Terrorists have been described as sociopaths , narcissists, fanatics, extremists, zealots, true-believers, jihadists or demented criminals...If terrorists are sociopaths or other deviants (and it is probable that some are), then it is unlikely that deterrence with its reliance on rational

A Multidimensional Strategy to Detect Polypharmacological Targets in the Absence of Structural and Sequence Homology

PubMed Central

Durrant, Jacob D.; Amaro, Rommie E.; Xie, Lei; Urbaniak, Michael D.; Ferguson, Michael A. J.; Haapalainen, Antti; Chen, Zhijun; Di Guilmi, Anne Marie; Wunder, Frank; Bourne, Philip E.; McCammon, J. Andrew

2010-01-01

Conventional drug design embraces the “one gene, one drug, one disease” philosophy. Polypharmacology, which focuses on multi-target drugs, has emerged as a new paradigm in drug discovery. The rational design of drugs that act via polypharmacological mechanisms can produce compounds that exhibit increased therapeutic potency and against which resistance is less likely to develop. Additionally, identifying multiple protein targets is also critical for side-effect prediction. One third of potential therapeutic compounds fail in clinical trials or are later removed from the market due to unacceptable side effects often caused by off-target binding. In the current work, we introduce a multidimensional strategy for the identification of secondary targets of known small-molecule inhibitors in the absence of global structural and sequence homology with the primary target protein. To demonstrate the utility of the strategy, we identify several targets of 4,5-dihydroxy-3-(1-naphthyldiazenyl)-2,7-naphthalenedisulfonic acid, a known micromolar inhibitor of Trypanosoma brucei RNA editing ligase 1. As it is capable of identifying potential secondary targets, the strategy described here may play a useful role in future efforts to reduce drug side effects and/or to increase polypharmacology. PMID:20098496

A multidimensional strategy to detect polypharmacological targets in the absence of structural and sequence homology.

PubMed

Durrant, Jacob D; Amaro, Rommie E; Xie, Lei; Urbaniak, Michael D; Ferguson, Michael A J; Haapalainen, Antti; Chen, Zhijun; Di Guilmi, Anne Marie; Wunder, Frank; Bourne, Philip E; McCammon, J Andrew

2010-01-22

Conventional drug design embraces the "one gene, one drug, one disease" philosophy. Polypharmacology, which focuses on multi-target drugs, has emerged as a new paradigm in drug discovery. The rational design of drugs that act via polypharmacological mechanisms can produce compounds that exhibit increased therapeutic potency and against which resistance is less likely to develop. Additionally, identifying multiple protein targets is also critical for side-effect prediction. One third of potential therapeutic compounds fail in clinical trials or are later removed from the market due to unacceptable side effects often caused by off-target binding. In the current work, we introduce a multidimensional strategy for the identification of secondary targets of known small-molecule inhibitors in the absence of global structural and sequence homology with the primary target protein. To demonstrate the utility of the strategy, we identify several targets of 4,5-dihydroxy-3-(1-naphthyldiazenyl)-2,7-naphthalenedisulfonic acid, a known micromolar inhibitor of Trypanosoma brucei RNA editing ligase 1. As it is capable of identifying potential secondary targets, the strategy described here may play a useful role in future efforts to reduce drug side effects and/or to increase polypharmacology.

Taking emotion seriously: meeting students where they are.

PubMed

Sunderland, Mary E

2014-03-01

Emotions are often portrayed as subjective judgments that pose a threat to rationality and morality, but there is a growing literature across many disciplines that emphasizes the centrality of emotion to moral reasoning. For engineers, however, being rational usually means sequestering emotions that might bias analyses-good reasoning is tied to quantitative data, math, and science. This paper brings a new pedagogical perspective that strengthens the case for incorporating emotions into engineering ethics. Building on the widely established success of active and collaborative learning environments, in particular the problem-based learning (PBL) philosophy and methodology, the paper articulates new strategies for incorporating emotion into engineering ethics education. An ethics education pilot study is analyzed to explore how PBL can engage students' emotions. Evidence suggests that PBL empowers students to cultivate value for engineering ethics and social responsibility, and in doing so, redefine the societal role of the engineer. Taking students' emotions seriously in engineering ethics offers an effective strategy to meaningfully engage students in ethical learning.

Untangling complex networks: risk minimization in financial markets through accessible spin glass ground states

PubMed Central

Lisewski, Andreas Martin; Lichtarge, Olivier

2010-01-01

Recurrent international financial crises inflict significant damage to societies and stress the need for mechanisms or strategies to control risk and tamper market uncertainties. Unfortunately, the complex network of market interactions often confounds rational approaches to optimize financial risks. Here we show that investors can overcome this complexity and globally minimize risk in portfolio models for any given expected return, provided the relative margin requirement remains below a critical, empirically measurable value. In practice, for markets with centrally regulated margin requirements, a rational stabilization strategy would be keeping margins small enough. This result follows from ground states of the random field spin glass Ising model that can be calculated exactly through convex optimization when relative spin coupling is limited by the norm of the network's Laplacian matrix. In that regime, this novel approach is robust to noise in empirical data and may be also broadly relevant to complex networks with frustrated interactions that are studied throughout scientific fields. PMID:20625477

When I cut, you choose method implies intransitivity

NASA Astrophysics Data System (ADS)

Makowski, Marcin; Piotrowski, Edward W.

2014-12-01

There is a common belief that humans and many animals follow transitive inference (choosing A over C on the basis of knowing that A is better than B and B is better than C). Transitivity seems to be the essence of rational choice. We present a theoretical model of a repeated game in which the players make a choice between three goods (e.g. food). The rules of the game refer to the simple procedure of fair division among two players, known as the “I cut, you choose” mechanism which has been widely discussed in the literature. In this game one of the players has to make intransitive choices in order to achieve the optimal result (for him/her and his/her co-player). The point is that an intransitive choice can be rational. Previously, an increase in the significance of intransitive strategies was achieved by referring to models of quantum games. We show that relevant intransitive strategies also appear in the classic description of decision algorithms.

Untangling complex networks: Risk minimization in financial markets through accessible spin glass ground states

NASA Astrophysics Data System (ADS)

Lisewski, Andreas Martin; Lichtarge, Olivier

2010-08-01

Recurrent international financial crises inflict significant damage to societies and stress the need for mechanisms or strategies to control risk and tamper market uncertainties. Unfortunately, the complex network of market interactions often confounds rational approaches to optimize financial risks. Here we show that investors can overcome this complexity and globally minimize risk in portfolio models for any given expected return, provided the margin requirement remains below a critical, empirically measurable value. In practice, for markets with centrally regulated margin requirements, a rational stabilization strategy would be keeping margins small enough. This result follows from ground states of the random field spin glass Ising model that can be calculated exactly through convex optimization when relative spin coupling is limited by the norm of the network’s Laplacian matrix. In that regime, this novel approach is robust to noise in empirical data and may be also broadly relevant to complex networks with frustrated interactions that are studied throughout scientific fields.

Rational Design of a Transferrin-Binding Peptide Sequence Tailored to Targeted Nanoparticle Internalization.

PubMed

Santi, Melissa; Maccari, Giuseppe; Mereghetti, Paolo; Voliani, Valerio; Rocchiccioli, Silvia; Ucciferri, Nadia; Luin, Stefano; Signore, Giovanni

2017-02-15

The transferrin receptor (TfR) is a promising target in cancer therapy owing to its overexpression in most solid tumors and on the blood-brain barrier. Nanostructures chemically derivatized with transferrin are employed in TfR targeting but often lose their functionality upon injection in the bloodstream. As an alternative strategy, we rationally designed a peptide coating able to bind transferrin on suitable pockets not involved in binding to TfR or iron by using an iterative multiscale-modeling approach coupled with quantitative structure-activity and relationship (QSAR) analysis and evolutionary algorithms. We tested that selected sequences have low aspecific protein adsorption and high binding energy toward transferrin, and one of them is efficiently internalized in cells with a transferrin-dependent pathway. Furthermore, it promotes transferrin-mediated endocytosis of gold nanoparticles by modifying their protein corona and promoting oriented adsorption of transferrin. This strategy leads to highly effective nanostructures, potentially useful in diagnostic and therapeutic applications, which exploit (and do not suffer) the protein solvation for achieving a better targeting.

Programmed coherent coupling in a synthetic DNA-based excitonic circuit

NASA Astrophysics Data System (ADS)

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

2018-02-01

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

Untangling complex networks: risk minimization in financial markets through accessible spin glass ground states.

PubMed

Lisewski, Andreas Martin; Lichtarge, Olivier

2010-08-15

Recurrent international financial crises inflict significant damage to societies and stress the need for mechanisms or strategies to control risk and tamper market uncertainties. Unfortunately, the complex network of market interactions often confounds rational approaches to optimize financial risks. Here we show that investors can overcome this complexity and globally minimize risk in portfolio models for any given expected return, provided the relative margin requirement remains below a critical, empirically measurable value. In practice, for markets with centrally regulated margin requirements, a rational stabilization strategy would be keeping margins small enough. This result follows from ground states of the random field spin glass Ising model that can be calculated exactly through convex optimization when relative spin coupling is limited by the norm of the network's Laplacian matrix. In that regime, this novel approach is robust to noise in empirical data and may be also broadly relevant to complex networks with frustrated interactions that are studied throughout scientific fields.

The Rational Hybrid Monte Carlo algorithm

NASA Astrophysics Data System (ADS)

Clark, Michael

2006-12-01

The past few years have seen considerable progress in algorithmic development for the generation of gauge fields including the effects of dynamical fermions. The Rational Hybrid Monte Carlo (RHMC) algorithm, where Hybrid Monte Carlo is performed using a rational approximation in place the usual inverse quark matrix kernel is one of these developments. This algorithm has been found to be extremely beneficial in many areas of lattice QCD (chiral fermions, finite temperature, Wilson fermions etc.). We review the algorithm and some of these benefits, and we compare against other recent algorithm developements. We conclude with an update of the Berlin wall plot comparing costs of all popular fermion formulations.

Fostering Non-Cognitive Development of Underrepresented Students through Rational Emotive Behavior Therapy: Recommendations for School Counselor Practice

ERIC Educational Resources Information Center

Warren, Jeffrey M.; Hale, Robyn W.

2016-01-01

The non-cognitive factors (NCFs) endorsed by Sedlacek (2004) appear to align with the core values of rational emotive behavior therapy (REBT). This article explores theoretical and empirical evidence that suggests REBT fosters the development of NCFs. School counselors can promote non-cognitive development by embedding REBT throughout direct and…

The influence of diet composition upon growth and development of sandhill cranes

USGS Publications Warehouse

Serafin, J.A.

1982-01-01

Experiments were conducted to evaluate the effect of protein, metabolizable energy, and sulfur amino acid content of five diets upon growth and development of captive Florida Sandhill Crane (Grus canadensis pratensis) and Greater Sandhill Crane (G. c. tabida) chicks raised under controlled conditions. A high protein (32%) diet resulted in faster growth than that obtained when a lower protein (24%) ration was supplied. Florida Sandhill Crane chicks fed a diet containing 2,160 kcal/kg grew significantly slower than chicks fed a ration containing 2,830 kcal/kg. Reducing the sulfur amino acid content of a ration containing 24% protein from 0.88% to 0.73% significantly slowed the growth of young cranes. A 17% incidence of leg disorders and a 25% incidence of wing abnormalities occurred between 7 and 28 days of age among Greater Sandhill Cranes fed a high protein diet. Florida Sandhill Cranes grew slower than Greater Sandhill Cranes irrespective of the type of ration they were provided and did not develop leg or wing abnormalities. Abnormalities invariably developed only in the most rapidly growing Greater Sandhill Cranes. Diets that promoted slower growth reduced the incidence of abnormalities. A ration formulated to contain a low (0.73%) sulfur amino acid level appeared to be the most suitable for slowing growth rates of captive-reared Sandhill Cranes and reducing the risk of abnormaiwing or leg development.

Chemical Kinetics for Bridging Molecular Mechanisms and Macroscopic Measurements of Amyloid Fibril Formation.

PubMed

Michaels, Thomas C T; Šarić, Anđela; Habchi, Johnny; Chia, Sean; Meisl, Georg; Vendruscolo, Michele; Dobson, Christopher M; Knowles, Tuomas P J

2018-04-20

Understanding how normally soluble peptides and proteins aggregate to form amyloid fibrils is central to many areas of modern biomolecular science, ranging from the development of functional biomaterials to the design of rational therapeutic strategies against increasingly prevalent medical conditions such as Alzheimer's and Parkinson's diseases. As such, there is a great need to develop models to mechanistically describe how amyloid fibrils are formed from precursor peptides and proteins. Here we review and discuss how ideas and concepts from chemical reaction kinetics can help to achieve this objective. In particular, we show how a combination of theory, experiments, and computer simulations, based on chemical kinetics, provides a general formalism for uncovering, at the molecular level, the mechanistic steps that underlie the phenomenon of amyloid fibril formation.

Kinetic modeling of cell metabolism for microbial production.

PubMed

Costa, Rafael S; Hartmann, Andras; Vinga, Susana

2016-02-10

Kinetic models of cellular metabolism are important tools for the rational design of metabolic engineering strategies and to explain properties of complex biological systems. The recent developments in high-throughput experimental data are leading to new computational approaches for building kinetic models of metabolism. Herein, we briefly survey the available databases, standards and software tools that can be applied for kinetic models of metabolism. In addition, we give an overview about recently developed ordinary differential equations (ODE)-based kinetic models of metabolism and some of the main applications of such models are illustrated in guiding metabolic engineering design. Finally, we review the kinetic modeling approaches of large-scale networks that are emerging, discussing their main advantages, challenges and limitations. Copyright © 2015 Elsevier B.V. All rights reserved.

Targeting the Thioredoxin System for Cancer Therapy.

PubMed

Zhang, Junmin; Li, Xinming; Han, Xiao; Liu, Ruijuan; Fang, Jianguo

2017-09-01

Thioredoxin (Trx) and thioredoxin reductase (TrxR) are essential components of the Trx system which plays pivotal roles in regulating multiple cellular redox signaling pathways. In recent years TrxR/Trx have been increasingly recognized as an important modulator of tumor development, and hence targeting TrxR/Trx is a promising strategy for cancer treatment. In this review we first discuss the structural details of TrxR, the functions of the Trx system, and the rational of targeting TrxR/Trx for cancer treatment. We also highlight small-molecule TrxR/Trx inhibitors that have potential anticancer activity and review their mechanisms of action. Finally, we examine the challenges of developing TrxR/Trx inhibitors as anticancer agents and perspectives for selectively targeting TrxR/Trx. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical Kinetics for Bridging Molecular Mechanisms and Macroscopic Measurements of Amyloid Fibril Formation

NASA Astrophysics Data System (ADS)

Michaels, Thomas C. T.; Šarić, Anđela; Habchi, Johnny; Chia, Sean; Meisl, Georg; Vendruscolo, Michele; Dobson, Christopher M.; Knowles, Tuomas P. J.

2018-04-01

Understanding how normally soluble peptides and proteins aggregate to form amyloid fibrils is central to many areas of modern biomolecular science, ranging from the development of functional biomaterials to the design of rational therapeutic strategies against increasingly prevalent medical conditions such as Alzheimer's and Parkinson's diseases. As such, there is a great need to develop models to mechanistically describe how amyloid fibrils are formed from precursor peptides and proteins. Here we review and discuss how ideas and concepts from chemical reaction kinetics can help to achieve this objective. In particular, we show how a combination of theory, experiments, and computer simulations, based on chemical kinetics, provides a general formalism for uncovering, at the molecular level, the mechanistic steps that underlie the phenomenon of amyloid fibril formation.

Synthetic approaches to construct viral capsid-like spherical nanomaterials.

PubMed

Matsuura, Kazunori

2018-06-06

This feature article describes recent progress in synthetic strategies to construct viral capsid-like spherical nanomaterials using the self-assembly of peptides and/or proteins. By mimicking the self-assembly of spherical viral capsids and clathrin, trigonal peptide conjugates bearing β-sheet-forming peptides, glutathiones, or coiled-coil-forming peptides were developed to construct viral capsid-like particles. β-Annulus peptides from tomato bushy stunt virus self-assembled into viral capsid-like nanocapsules with a size of 30-50 nm, which could encapsulate various guest molecules and be decorated with different molecules on their surface. Rationally designed fusion proteins bearing symmetric assembling units afforded precise viral capsid-like polyhedral assemblies. These synthetic approaches to construct artificial viruses could become useful guidelines to develop novel drug carriers, vaccine platforms, nanotemplates and nanoreactors.

Homo heuristicus: why biased minds make better inferences.

PubMed

Gigerenzer, Gerd; Brighton, Henry

2009-01-01

Heuristics are efficient cognitive processes that ignore information. In contrast to the widely held view that less processing reduces accuracy, the study of heuristics shows that less information, computation, and time can in fact improve accuracy. We review the major progress made so far: (a) the discovery of less-is-more effects; (b) the study of the ecological rationality of heuristics, which examines in which environments a given strategy succeeds or fails, and why; (c) an advancement from vague labels to computational models of heuristics; (d) the development of a systematic theory of heuristics that identifies their building blocks and the evolved capacities they exploit, and views the cognitive system as relying on an "adaptive toolbox;" and (e) the development of an empirical methodology that accounts for individual differences, conducts competitive tests, and has provided evidence for people's adaptive use of heuristics. Homo heuristicus has a biased mind and ignores part of the available information, yet a biased mind can handle uncertainty more efficiently and robustly than an unbiased mind relying on more resource-intensive and general-purpose processing strategies. Copyright © 2009 Cognitive Science Society, Inc.

A Review of PAT Strategies in Secondary Solid Oral Dosage Manufacturing of Small Molecules.

PubMed

Laske, Stephan; Paudel, Amrit; Scheibelhofer, Otto

2017-03-01

Pharmaceutical solid oral dosage product manufacturing is a well-established, yet revolutionizing area. To this end, process analytical technology (PAT) involves interdisciplinary and multivariate (chemical, physical, microbiological, and mathematical) methods for material (e.g., materials, intermediates, products) and process (e.g., temperature, pressure, throughput, etc.) analysis. This supports rational process modeling and enhanced control strategies for improved product quality and process efficiency. Therefore, it is often difficult to orient and find the relevant, integrated aspects of the current state-of-the-art. Especially, the link between fundamental research, in terms of sensor and control system development, to the application both in laboratory and manufacturing scale, is difficult to comprehend. This review compiles a nonexhaustive overview on current approaches from the recognized academia and industrial practices of PAT, including screening, selection, and final implementations in solid oral dosage manufacturing, through a wide diversity of use cases. Finally, the authors attempt to extract a common consensus toward developing PAT application guidance for different unit operations of drug product manufacturing. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Design Strategy of Multi-electron Transfer Catalysts Based on a Bioinformatic Analysis of Oxygen Evolution and Reduction Enzymes.

PubMed

Ooka, Hideshi; Hashimoto, Kazuhito; Nakamura, Ryuhei

2018-05-14

Understanding the design strategy of photosynthetic and respiratory enzymes is important to develop efficient artificial catalysts for oxygen evolution and reduction reactions. Here, based on a bioinformatic analysis of cyanobacterial oxygen evolution and reduction enzymes (photosystem II: PS II and cytochrome c oxidase: COX, respectively), the gene encoding the catalytic D1 subunit of PS II was found to be expressed individually across 38 phylogenetically diverse strains, which is in contrast to the operon structure of the genes encoding major COX subunits. Selective synthesis of the D1 subunit minimizes the repair cost of PS II, which allows compensation for its instability by lowering the turnover number required to generate a net positive energy yield. The different bioenergetics observed between PS II and COX suggest that in addition to the catalytic activity rationalized by the Sabatier principle, stability factors have also provided a major influence on the design strategy of biological multi-electron transfer enzymes. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Feminist Supervision Scale: A Rational/Theoretical Approach

ERIC Educational Resources Information Center

Szymanski, Dawn M.

2003-01-01

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

Living, Being, Eating: Decisions We Make.

ERIC Educational Resources Information Center

Georgia State Dept. of Education, Atlanta. Office of Vocational Education.

Developed for use in the Youth Development Center of Georgia, these fifteen lessons respond to a need for nutrition education and training. Lesson titles are (1) Pre-Test and Brainstorming Exercises; (2) Moods and Emotions; (3) Reasons (rational vs. emotional thinking); (4) Two Sides of an Issue (rational, emotional, and combination thinking;…

Public sector energy management: A strategy for catalyzing energy efficiency in Malaysia

NASA Astrophysics Data System (ADS)

Roy, Anish Kumar

To date the public sector role in facilitating the transition to a sustainable energy future has been envisaged mainly from a regulatory perspective. In such a role, the public sector provides the push factors---enforcing regulations and providing incentives---to correct market imperfections that impede energy transitions. An alternative and complementary role of the public sector that is now gaining increasing attention is that of catalyzing energy transitions through public sector energy management initiatives. This dissertation offers a conceptual framework to rationalize such a role for the public sector by combining recent theories of sustainable energy transition and public management. In particular, the framework identifies innovative public management strategies (such as performance contracting and procurement) for effectively implementing sustainable energy projects in government facilities. The dissertation evaluates a model of sustainable public sector energy management for promoting energy efficiency in Malaysia. The public sector in Malaysia can be a major player in leading and catalyzing energy efficiency efforts as it is not only the largest and one of the most influential energy consumers, but it also plays a central role in setting national development strategy. The dissertation makes several recommendations on how a public sector energy management strategy can be implemented in Malaysia. The US Federal Energy Management Program (FEMP) is used as a practical model. The analysis, however, shows that in applying the FEMP model to the Malaysian context, there are a number of limitations that will have to be taken into consideration to enable a public sector energy management strategy to be effectively implemented. Overall the analysis of this dissertation contributes to a rethinking of the public sector role in sustainable energy development that can strengthen the sector's credibility both in terms of governance and institutional performance. In addition, it links theory with practice by offering a strategy that can effectively address critical issues arising from the energy-development-policy nexus of the sustainable energy development debate.

Current Strategies for Inhibition of Chikungunya Infection.

PubMed

Subudhi, Bharat Bhusan; Chattopadhyay, Soma; Mishra, Priyadarsee; Kumar, Abhishek

2018-05-03

Increasing incidences of Chikungunya virus (CHIKV) infection and co-infections with Dengue/Zika virus have highlighted the urgency for CHIKV management. Failure in developing effective vaccines or specific antivirals has fuelled further research. This review discusses updated strategies of CHIKV inhibition and provides possible future directions. In addition, it analyzes advances in CHIKV lifecycle, drug-target development, and potential hits obtained by in silico and experimental methods. Molecules identified with anti-CHIKV properties using traditional/rational drug design and their potential to succeed in subsequent stages of drug development have also been discussed. Possibilities of repurposing existing drugs based on their in vitro findings have also been elucidated. Probable modes of interference of these compounds at various stages of infection, including entry and replication, have been highlighted. The use of host factors as targets to identify antivirals against CHIKV has been addressed. While most of the earlier antivirals were effective in the early phases of the CHIKV life cycle, this review is also focused on drug candidates that are effective at multiple stages of its life cycle. Since most of these antivirals require validation in preclinical and clinical models, the challenges regarding this have been discussed and will provide critical information for further research.

Current Strategies for Inhibition of Chikungunya Infection

PubMed Central

Subudhi, Bharat Bhusan; Chattopadhyay, Soma; Mishra, Priyadarsee

2018-01-01

Increasing incidences of Chikungunya virus (CHIKV) infection and co-infections with Dengue/Zika virus have highlighted the urgency for CHIKV management. Failure in developing effective vaccines or specific antivirals has fuelled further research. This review discusses updated strategies of CHIKV inhibition and provides possible future directions. In addition, it analyzes advances in CHIKV lifecycle, drug-target development, and potential hits obtained by in silico and experimental methods. Molecules identified with anti-CHIKV properties using traditional/rational drug design and their potential to succeed in subsequent stages of drug development have also been discussed. Possibilities of repurposing existing drugs based on their in vitro findings have also been elucidated. Probable modes of interference of these compounds at various stages of infection, including entry and replication, have been highlighted. The use of host factors as targets to identify antivirals against CHIKV has been addressed. While most of the earlier antivirals were effective in the early phases of the CHIKV life cycle, this review is also focused on drug candidates that are effective at multiple stages of its life cycle. Since most of these antivirals require validation in preclinical and clinical models, the challenges regarding this have been discussed and will provide critical information for further research. PMID:29751486

The biology of sexual development of Plasmodium: the design and implementation of transmission-blocking strategies.

PubMed

Sinden, Robert E; Carter, Richard; Drakeley, Chris; Leroy, Didier

2012-03-16

A meeting to discuss the latest developments in the biology of sexual development of Plasmodium and transmission-control was held April 5-6, 2011, in Bethesda, MD. The meeting was sponsored by the Bill & Melinda Gates Foundation and the National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIH/NIAID) in response to the challenge issued at the Malaria Forum in October 2007 that the malaria community should re-engage with the objective of global eradication. The consequent rebalancing of research priorities has brought to the forefront of the research agenda the essential need to reduce parasite transmission. A key component of any transmission reduction strategy must be methods to attack the parasite as it passes from man to the mosquito (and vice versa). Such methods must be rationally based on a secure understanding of transmission from the molecular-, cellular-, population- to the evolutionary-levels. The meeting represented a first attempt to draw together scientists with expertise in these multiple layers of understanding to discuss the scientific foundations and resources that will be required to provide secure progress toward the design and successful implementation of effective interventions.

Rational, computer-enabled peptide drug design: principles, methods, applications and future directions.

PubMed

Diller, David J; Swanson, Jon; Bayden, Alexander S; Jarosinski, Mark; Audie, Joseph

2015-01-01

Peptides provide promising templates for developing drugs to occupy a middle space between small molecules and antibodies and for targeting 'undruggable' intracellular protein-protein interactions. Importantly, rational or in cerebro design, especially when coupled with validated in silico tools, can be used to efficiently explore chemical space and identify islands of 'drug-like' peptides to satisfy diverse drug discovery program objectives. Here, we consider the underlying principles of and recent advances in rational, computer-enabled peptide drug design. In particular, we consider the impact of basic physicochemical properties, potency and ADME/Tox opportunities and challenges, and recently developed computational tools for enabling rational peptide drug design. Key principles and practices are spotlighted by recent case studies. We close with a hypothetical future case study.

The Development of Rational Imitation in 9- and 12-Month-Old Infants

ERIC Educational Resources Information Center

Zmyj, Norbert; Daum, Moritz M.; Aschersleben, Gisa

2009-01-01

Studies on rational imitation have provided evidence for the fact that infants as young as 12 months of age engage in rational imitation. However, the developmental onset of this ability is unclear. In this study, we investigated whether 9- and 12-month-olds detect voluntary and implicit as well as nonvoluntary and explicit constraints in the head…

Inappropriately Applying Natural Number Properties in Rational Number Tasks: Characterizing the Development of the Natural Number Bias through Primary and Secondary Education

ERIC Educational Resources Information Center

van Hoof, Jo; Verschaffel, Lieven; van Dooren, Wim

2015-01-01

The natural number bias is known to explain many difficulties learners have with understanding rational numbers. The research field distinguishes three aspects where natural number properties are sometimes inappropriately applied in rational number tasks: density, size, and operations. The overall goal of this study was to characterize the…

[Problems in development of agriculture-animal husbandry ecotone and its countermeasures].

PubMed

Baoyin, Taogetao; Bai, Yongfei

2004-02-01

Problems in development of Duolun, a typical agriculture-animal husbandry ecotone, and its countermeasures were discussed in this paper. Economic structure was not rational in Duolun, and it should develop industry and commerce, limit the scope of agriculture and animal husbandry, and actively increase efficiency of agriculture and animal husbandry. The structure of land use was not rational, and the main countermeasures were to increase area of forestland and grassland, and decrease cultivated area. On resources use, the main countermeasures were to exploit water resource rationally and bring into play resource superiority of mutually benefits on agriculture and animal husbandry. The ecological environment construction was the foundation of the national economy for sustainable development in agriculture-animal husbandry ecotone.

SIGI: An Interactive Aid to Career Decision Making.

ERIC Educational Resources Information Center

Katz, Martin R.

1980-01-01

The System of Interactive Guidance and Information (SIGI) helps students make informed and rational career decisions. Interacting with a computer, students examine values, identify and explore options, gain and interpret relevant information, master strategies for decision making, and formulate plans of action. Extensively field-tested, SIGI has…

The Rational Adolescent: Discipline Policies, Lawsuits, and Skill Acquisition

ERIC Educational Resources Information Center

Babcock, Philip

2009-01-01

The paper estimates the response of student truancy and long-run labor market outcomes to discipline policies in middle and secondary school. Simultaneous determination of student behaviors and school policies motivates an instrumental variables strategy. Because judicial climate influences administrators' fear of discipline-related lawsuits,…

The Rescue from Relativism: Two Failed Attempts and an Alternative Strategy.

ERIC Educational Resources Information Center

Donmoyer, Robert

1985-01-01

Critiques attempts to resurrect aspects of positivism and argues that the work of certain post-positivist philosophers (in particular, Toulmin's discussions of the role that purpose plays in rational decisionmaking) provides a more adequate response to the problems associated with relativism. (Author/GC)

Dilemmas in rationing health care services: the case for implicit rationing.

PubMed

Mechanic, D

1995-06-24

With tension between the demand for health services and the cost of providing them, rationing is increasingly evident in all medical systems. Until recently, rationing was primarily through the ability to pay or achieved implicitly by doctors working within fixed budgets. Such forms of rationing are commonly alleged to be inequitable and inefficient and explicit rationing is advocated as more appropriate. Utilisation management in the United States and quasi-markets separating purchasing from provision in the United Kingdom are seen as ways of using resources more efficiently and are increasingly explicit. There is also advocacy to ration explicitly at the point of service. Mechanic reviews the implications of these developments and explains why explicit approaches are likely to focus conflict and dissatisfaction and be politically unstable. Explicit rationing is unlikely to be as equitable as its proponents argue and is likely to make dissatisfaction and perceived deprivation more salient. Despite its limitations, implicit rationing at the point of service is more sensitive to the complexity of medical decisions and the needs and personal and cultural preferences of patients. All systems use a mix of rationing devices, but the clinical allocation of services should substantially depend on the discretion of professionals informed by practice guidelines, outcomes research, and other informational aids.

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

PubMed

Strech, Daniel

2011-01-01

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

Dilemmas in rationing health care services: the case for implicit rationing.

PubMed Central

Mechanic, D.

1995-01-01

With tension between the demand for health services and the cost of providing them, rationing is increasingly evident in all medical systems. Until recently, rationing was primarily through the ability to pay or achieved implicitly by doctors working within fixed budgets. Such forms of rationing are commonly alleged to be inequitable and inefficient and explicit rationing is advocated as more appropriate. Utilisation management in the United States and quasi-markets separating purchasing from provision in the United Kingdom are seen as ways of using resources more efficiently and are increasingly explicit. There is also advocacy to ration explicitly at the point of service. Mechanic reviews the implications of these developments and explains why explicit approaches are likely to focus conflict and dissatisfaction and be politically unstable. Explicit rationing is unlikely to be as equitable as its proponents argue and is likely to make dissatisfaction and perceived deprivation more salient. Despite its limitations, implicit rationing at the point of service is more sensitive to the complexity of medical decisions and the needs and personal and cultural preferences of patients. All systems use a mix of rationing devices, but the clinical allocation of services should substantially depend on the discretion of professionals informed by practice guidelines, outcomes research, and other informational aids. Images p1657-a p1659-a PMID:7795458

Perspective: deconstructing integration: a framework for the rational application of integration as a guiding curricular strategy.

PubMed

Goldman, Ellen; Schroth, W Scott

2012-06-01

In response to historical criticism, evolving accreditation standards, and recent reports on curricula, medical educators and medical schools have been eagerly pursuing integration as a goal of curricular reform. The general education literature broadly considers integration to be the deliberate unification of separate areas of knowledge, and it provides support for the concept that integration better meets the needs of adult learners in professional education. The use of integration as a curricular goal is not without its critics, however, nor is it free of difficulties in implementation. In this perspective, the authors propose that most of these difficulties arise from a failure to recognize that integration is a strategy for curricular development rather than a goal in itself, and they argue that adopting a systematic approach to integration offers many potential benefits. They articulate the conceptual and practical issues that they believe are critical to consider in order to achieve successful curricular integration, and they suggest that integration should be approached as a subset of broader curriculum development decisions. They propose a three-level framework for applying integration as a guiding curricular strategy, in which decisions about integration must follow curricular decisions made at the program level, the course level, and then the individual session level.

Total Brain Death and the Integration of the Body Required of a Human Being

PubMed Central

Lee, Patrick

2016-01-01

I develop and refine an argument for the total brain death criterion of death previously advanced by Germain Grisez and me: A human being is essentially a rational animal, and so must have a radical capacity for rational operations. For rational animals, conscious sensation is a pre-requisite for rational operation. But total brain death results in the loss of the radical capacity for conscious sensation, and so also for rational operations. Hence, total brain death constitutes a substantial change—the ceasing to be of the human being. Objections are considered, including the objection that total brain death need not result in the loss of capacity for sensation, and that damage to the brain less than total brain death can result in loss of capacity for rational operations. PMID:27097647

Cognitive costs of decision-making strategies: A resource demand decomposition analysis with a cognitive architecture.

PubMed

Fechner, Hanna B; Schooler, Lael J; Pachur, Thorsten

2018-01-01

Several theories of cognition distinguish between strategies that differ in the mental effort that their use requires. But how can the effort-or cognitive costs-associated with a strategy be conceptualized and measured? We propose an approach that decomposes the effort a strategy requires into the time costs associated with the demands for using specific cognitive resources. We refer to this approach as resource demand decomposition analysis (RDDA) and instantiate it in the cognitive architecture Adaptive Control of Thought-Rational (ACT-R). ACT-R provides the means to develop computer simulations of the strategies. These simulations take into account how strategies interact with quantitative implementations of cognitive resources and incorporate the possibility of parallel processing. Using this approach, we quantified, decomposed, and compared the time costs of two prominent strategies for decision making, take-the-best and tallying. Because take-the-best often ignores information and foregoes information integration, it has been considered simpler than strategies like tallying. However, in both ACT-R simulations and an empirical study we found that under increasing cognitive demands the response times (i.e., time costs) of take-the-best sometimes exceeded those of tallying. The RDDA suggested that this pattern is driven by greater requirements for working memory updates, memory retrievals, and the coordination of mental actions when using take-the-best compared to tallying. The results illustrate that assessing the relative simplicity of strategies requires consideration of the overall cognitive system in which the strategies are embedded. Copyright © 2017 Elsevier B.V. All rights reserved.

A testing strategy to predict risk for drug-induced liver injury in humans using high-content screen assays and the 'rule-of-two' model.

PubMed

Chen, Minjun; Tung, Chun-Wei; Shi, Qiang; Guo, Lei; Shi, Leming; Fang, Hong; Borlak, Jürgen; Tong, Weida

2014-07-01

Drug-induced liver injury (DILI) is a major cause of drug failures in both the preclinical and clinical phase. Consequently, improving prediction of DILI at an early stage of drug discovery will reduce the potential failures in the subsequent drug development program. In this regard, high-content screening (HCS) assays are considered as a promising strategy for the study of DILI; however, the predictive performance of HCS assays is frequently insufficient. In the present study, a new testing strategy was developed to improve DILI prediction by employing in vitro assays that was combined with the RO2 model (i.e., 'rule-of-two' defined by daily dose ≥100 mg/day & logP ≥3). The RO2 model was derived from the observation that high daily doses and lipophilicity of an oral medication were associated with significant DILI risk in humans. In the developed testing strategy, the RO2 model was used for the rational selection of candidates for HCS assays, and only the negatives predicted by the RO2 model were further investigated by HCS. Subsequently, the effects of drug treatment on cell loss, nuclear size, DNA damage/fragmentation, apoptosis, lysosomal mass, mitochondrial membrane potential, and steatosis were studied in cultures of primary rat hepatocytes. Using a set of 70 drugs with clear evidence of clinically relevant DILI, the testing strategy improved the accuracies by 10 % and reduced the number of drugs requiring experimental assessment by approximately 20 %, as compared to the HCS assay alone. Moreover, the testing strategy was further validated by including published data (Cosgrove et al. in Toxicol Appl Pharmacol 237:317-330, 2009) on drug-cytokine-induced hepatotoxicity, which improved the accuracies by 7 %. Taken collectively, the proposed testing strategy can significantly improve the prediction of in vitro assays for detecting DILI liability in an early drug discovery phase.

Social Learning in the Ultimatum Game

PubMed Central

Zhang, Boyu

2013-01-01

In the ultimatum game, two players divide a sum of money. The proposer suggests how to split and the responder can accept or reject. If the suggestion is rejected, both players get nothing. The rational solution is that the responder accepts even the smallest offer but humans prefer fair share. In this paper, we study the ultimatum game by a learning-mutation process based on quantal response equilibrium, where players are assumed boundedly rational and make mistakes when estimating the payoffs of strategies. Social learning is never stabilized at the fair outcome or the rational outcome, but leads to oscillations from offering 40 percent to 50 percent. To be precise, there is a clear tendency to increase the mean offer if it is lower than 40 percent, but will decrease when it reaches the fair offer. If mutations occur rarely, fair behavior is favored in the limit of local mutation. If mutation rate is sufficiently high, fairness can evolve for both local mutation and global mutation. PMID:24023950

Evolution of Cooperation in Public Goods Games

NASA Astrophysics Data System (ADS)

Xia, Cheng-Yi; Zhang, Juan-Juan; Wang, Yi-Ling; Wang, Jin-Song

2011-10-01

We investigate the evolution of cooperation with evolutionary public goods games based on finite populations, where four pure strategies: cooperators, defectors, punishers and loners who are unwilling to participate are considered. By adopting approximate best response dynamics, we show that the magnitude of rationality not only quantitatively explains the experiment results in [Nature (London) 425 (2003) 390], but also it will heavily influence the evolution of cooperation. Compared with previous results of infinite populations, which result in two equilibriums, we show that there merely exists a special equilibrium and the relevant high value of bounded rationality will sustain cooperation. In addition, we characterize that loner's payoff plays an active role in the maintenance of cooperation, which will only be warranted for the low and moderate values of loner's payoff. It thus indicates the effects of rationality and loner's payoff will influence the cooperation. Finally, we highlight the important result that the introduction of voluntary participation and punishment will facilitate cooperation greatly.

Strategies and challenges for safe injection practice in developing countries.

PubMed

Gyawali, Sudesh; Rathore, Devendra Singh; Shankar, P Ravi; Kumar, Kc Vikash

2013-01-01

Injection is one of the important health care procedures used globally to administer drugs. Its unsafe use can transmit various blood borne pathogens. This article aims to review the history and status of injection practices, its importance, interventions and the challenges for safe injection practice in developing countries. The history of injections started with the discovery of syringe in the early nineteenth century. Safe injection practice in developed countries was initiated in the early twentieth century but has not received adequate attention in developing countries. The establishment of "Safe Injection Global Network (SIGN)" was an milestone towards safe injection practice globally. In developing countries, people perceive injection as a powerful healing tool and do not hesitate to pay more for injections. Unsafe disposal and reuse of contaminated syringe is common. Ensuring safe injection practice is one of the greatest challenges for healthcare system in developing countries. To address the problem, interventions with active involvement of a number of stakeholders is essential. A combination of educational, managerial and regulatory strategies is found to be effective and economically viable. Rational and safe use of injections can save many lives but unsafe practice threatens life. Safe injection practice is crucial in developing countries. Evidence based interventions, with honest commitment and participation from the service provider, recipient and community with aid of policy makers are required to ensure safe injection practice.

Strategies and challenges for safe injection practice in developing countries

PubMed Central

Gyawali, Sudesh; Rathore, Devendra Singh; Shankar, P Ravi; Kumar, KC Vikash

2013-01-01

Injection is one of the important health care procedures used globally to administer drugs. Its unsafe use can transmit various blood borne pathogens. This article aims to review the history and status of injection practices, its importance, interventions and the challenges for safe injection practice in developing countries. The history of injections started with the discovery of syringe in the early nineteenth century. Safe injection practice in developed countries was initiated in the early twentieth century but has not received adequate attention in developing countries. The establishment of “Safe Injection Global Network (SIGN)” was an milestone towards safe injection practice globally. In developing countries, people perceive injection as a powerful healing tool and do not hesitate to pay more for injections. Unsafe disposal and reuse of contaminated syringe is common. Ensuring safe injection practice is one of the greatest challenges for healthcare system in developing countries. To address the problem, interventions with active involvement of a number of stakeholders is essential. A combination of educational, managerial and regulatory strategies is found to be effective and economically viable. Rational and safe use of injections can save many lives but unsafe practice threatens life. Safe injection practice is crucial in developing countries. Evidence based interventions, with honest commitment and participation from the service provider, recipient and community with aid of policy makers are required to ensure safe injection practice. PMID:23662018

Discovery of small molecules binding to the normal conformation of prion by combining virtual screening and multiple biological activity evaluation methods

NASA Astrophysics Data System (ADS)

Li, Lanlan; Wei, Wei; Jia, Wen-Juan; Zhu, Yongchang; Zhang, Yan; Chen, Jiang-Huai; Tian, Jiaqi; Liu, Huanxiang; He, Yong-Xing; Yao, Xiaojun

2017-12-01

Conformational conversion of the normal cellular prion protein, PrPC, into the misfolded isoform, PrPSc, is considered to be a central event in the development of fatal neurodegenerative diseases. Stabilization of prion protein at the normal cellular form (PrPC) with small molecules is a rational and efficient strategy for treatment of prion related diseases. However, few compounds have been identified as potent prion inhibitors by binding to the normal conformation of prion. In this work, to rational screening of inhibitors capable of stabilizing cellular form of prion protein, multiple approaches combining docking-based virtual screening, steady-state fluorescence quenching, surface plasmon resonance and thioflavin T fluorescence assay were used to discover new compounds interrupting PrPC to PrPSc conversion. Compound 3253-0207 that can bind to PrPC with micromolar affinity and inhibit prion fibrillation was identified from small molecule databases. Molecular dynamics simulation indicated that compound 3253-0207 can bind to the hotspot residues in the binding pocket composed by β1, β2 and α2, which are significant structure moieties in conversion from PrPC to PrPSc.

Alkali-Resistant Mechanism of a Hollandite DeNOx Catalyst.

PubMed

Hu, Pingping; Huang, Zhiwei; Gu, Xiao; Xu, Fei; Gao, Jiayi; Wang, Yue; Chen, Yaxin; Tang, Xingfu

2015-06-02

A thorough understanding of the deactivation mechanism by alkalis is of great importance for rationally designing improved alkali-resistant deNOx catalysts, but a traditional ion-exchange mechanism cannot often accurately describe the nature of the deactivation, thus hampering the development of superior catalysts. Here, we establish a new exchange-coordination mechanism on the basis of the exhaustive study on the strong alkali resistance of a hollandite manganese oxide (HMO) catalyst. A combination of isothermal adsorption measurements of ammonia with X-ray absorption near-edge structure spectra and X-ray photoelectron spectra reveals that alkali metal ions first react with protons from Brønsted acid sites of HMO via the ion exchange. Synchrotron X-ray diffraction patterns and extended X-ray absorption fine structure spectra coupled with theoretical calculations demonstrate that the exchanged alkali metal ions are subsequently stabilized at size-suitable cavities in the HMO pores via a coordination model with an energy savings. This exchange-coordination mechanism not only gives a wholly convincing explanation for the intrinsic nature of the deactivation of the reported catalysts by alkalis but also provides a strategy for rationally designing improved alkali-resistant deNOx catalysts in general.

Navigating the poverty of heroin addiction treatment and recovery opportunity in Kenya: access work, self-care and rationed expectations.

PubMed

Rhodes, Tim; Ndimbii, James; Guise, Andy; Cullen, Lucy; Ayon, Sylvia

2015-01-01

Drawing on the analyses of qualitative interview accounts of people who inject heroin in Kenya, we describe the narration of addiction treatment access and recovery desire in conditions characterised by a 'poverty of drug treatment opportunity'. We observe the performance of addiction recovery narrative in the face of heavy social constraints limiting access to care. Fee-based residential rehabilitation ('rehab') is the only treatment locally available and inaccessible to most. Its recovery potential is doubted, given normative expectations of relapse. Treating drug use is a product of tightly bounded agency. Individuals enact strategies to maximise their slim chances of treatment access ('access work'), develop self-care alternatives when these fail to materialise and ration their care expectations. The use of rehab as a primary means of respite and harm reduction rather than recovery and the individuation of care in the absence of an enabling recovery environment are key characteristics of drug treatment experience. The recent incorporation of 'harm reduction' into policy discourses may trouble the primacy of recovery narrative in addiction treatment and in how treatment desires are voiced. The diversification of drug treatments in combination with social interventions enabling their access are fundamental.

Improving Allocation And Management Of The Health Workforce In Zambia.

PubMed

Walsh, Fiona J; Musonda, Mutinta; Mwila, Jere; Prust, Margaret Lippitt; Vosburg, Kathryn Bradford; Fink, Günther; Berman, Peter; Rockers, Peter C

2017-05-01

Building a health workforce in low-income countries requires a focused investment of time and resources, and ministries of health need tools to create staffing plans and prioritize spending on staff for overburdened health facilities. In Zambia a demand-based workload model was developed to calculate the number of health workers required to meet demands for essential health services and inform a rational and optimized strategy for deploying new public-sector staff members to the country's health facilities. Between 2009 and 2011 Zambia applied this optimized deployment policy, allocating new health workers to areas with the greatest demand for services. The country increased its health worker staffing in districts with fewer than one health worker per 1,000 people by 25.2 percent, adding 949 health workers to facilities that faced severe staffing shortages. At facilities that had had low staffing levels, adding a skilled provider was associated with an additional 103 outpatient consultations per quarter. Policy makers in resource-limited countries should consider using strategic approaches to identifying and deploying a rational distribution of health workers to provide the greatest coverage of health services to their populations. Project HOPE—The People-to-People Health Foundation, Inc.

Engineering Shewanella oneidensis enables xylose-fed microbial fuel cell.

PubMed

Li, Feng; Li, Yuanxiu; Sun, Liming; Li, Xiaofei; Yin, Changji; An, Xingjuan; Chen, Xiaoli; Tian, Yao; Song, Hao

2017-01-01

The microbial fuel cell (MFC) is a green and sustainable technology for electricity energy harvest from biomass, in which exoelectrogens use metabolism and extracellular electron transfer pathways for the conversion of chemical energy into electricity. However, Shewanella oneidensis MR-1, one of the most well-known exoelectrogens, could not use xylose (a key pentose derived from hydrolysis of lignocellulosic biomass) for cell growth and power generation, which limited greatly its practical applications. Herein, to enable S. oneidensis to directly utilize xylose as the sole carbon source for bioelectricity production in MFCs, we used synthetic biology strategies to successfully construct four genetically engineered S. oneidensis (namely XE, GE, XS, and GS) by assembling one of the xylose transporters (from Candida intermedia and Clostridium acetobutylicum ) with one of intracellular xylose metabolic pathways (the isomerase pathway from Escherichia coli and the oxidoreductase pathway from Scheffersomyces stipites ), respectively. We found that among these engineered S. oneidensis strains, the strain GS (i.e. harbouring Gxf1 gene encoding the xylose facilitator from C. intermedi , and XYL1 , XYL2 , and XKS1 genes encoding the xylose oxidoreductase pathway from S. stipites ) was able to generate the highest power density, enabling a maximum electricity power density of 2.1 ± 0.1 mW/m 2 . To the best of our knowledge, this was the first report on the rationally designed Shewanella that could use xylose as the sole carbon source and electron donor to produce electricity. The synthetic biology strategies developed in this study could be further extended to rationally engineer other exoelectrogens for lignocellulosic biomass utilization to generate electricity power.

Using insights from behavioral economics and social psychology to help patients manage chronic diseases.

PubMed

Mogler, Braden K; Shu, Suzanne B; Fox, Craig R; Goldstein, Noah J; Victor, Ronald G; Escarce, José J; Shapiro, Martin F

2013-05-01

Despite a revolution in therapeutics, the ability to control chronic diseases remains elusive. We present here a conceptual model of the potential role of behavioral tools in chronic disease control. Clinicians implicitly accept the assumption that patients will act rationally to maximize their self-interest. However, patients may not always be the rational actors that we imagine. Major behavioral barriers to optimal health behavior include patients' fear of threats to health, unwillingness to think about problems when risks are known or data are ambiguous, the discounting of risks that are far in the future, failure to act due to lack of motivation, insufficient confidence in the ability to overcome a health problem, and inattention due to pressures of everyday life. Financial incentives can stimulate initiation of health-promoting behaviors by reducing or eliminating financial barriers, but may not produce long-term behavior change without additional interventions. Strategies have been developed by behavioral economists and social psychologists to address each of these barriers to better decision-making. These include: labeling positive behaviors in ways consistent with patient life goals and priorities; greater focus on more immediate risks of chronic diseases; intermediate subgoals as steps to a large health goal; and implementation of specific plans as to when, where, and how an action will be taken. Such strategies hold promise for improving health behaviors and disease control, but most have not been studied in medical settings. The effectiveness of these approaches should be evaluated for their potential as tools for the clinician.

Student Award for Outstanding Research Winner in the Ph.D. Category for the 9th World Biomaterials Congress, Chengdu, China, June 1-5, 2012: The interplay of bone-like extracellular matrix and TNF-α signaling on in vitro osteogenic differentiation of mesenchymal stem cells.

PubMed

Mountziaris, Paschalia M; Tzouanas, Stephanie N; Mikos, Antonios G

2012-05-01

As an initial step in the development of a bone tissue engineering strategy to rationally control inflammation, we investigated the interplay of bone-like extracellular matrix (ECM) and varying doses of the inflammatory cytokine tumor necrosis factor alpha (TNF-α) on osteogenically differentiating mesenchymal stem cells (MSCs) cultured in vitro on 3D poly(ε-caprolactone) (PCL) microfiber scaffolds containing pregenerated bone-like ECM. To generate the ECM, PCL scaffolds were seeded with MSCs and cultured in medium containing the typically required osteogenic supplement dexamethasone. However, since dexamethasone antagonizes TNF-α, the interplay of ECM and TNF-α was investigated by culturing naïve MSCs on the decellularized scaffolds in the absence of dexamethasone. MSCs cultured on ECM-coated scaffolds continued to deposit mineralized matrix, a late stage marker of osteogenic differentiation. Mineralized matrix deposition was not adversely affected by exposure to TNF-α for 4-8 days, but was significantly reduced after continuous exposure to TNF-α over 16 days, which simulates the in vivo response, where brief TNF-α signaling stimulates bone regeneration, while prolonged exposure has damaging effects. This underscores the exciting potential of PCL/ECM constructs as a more clinically realistic in vitro culture model to facilitate the design of new bone tissue engineering strategies that rationally control inflammation to promote regeneration. Copyright © 2012 Wiley Periodicals, Inc.

Male Youth Perceptions of Violent Extremism: towards a Test of Rational Choice Theory.

PubMed

Dhami, Mandeep K; Murray, Jennifer

2016-09-20

Understanding how people perceive the pros and cons of risky behaviors such as terrorism or violent extremism represents a first step in developing research testing rational choice theory aiming to explain and predict peoples' intentions to engage in, or support, these behaviors. Accordingly, the present study provides a qualitative, exploratory analysis of a sample of 57 male youths' perceptions of the benefits and drawbacks of: (a) accessing a violent extremist website, (b) joining a violent extremist group, and (c) leaving such a group. Youth perceived significantly more drawbacks than benefits of joining a violent extremist group (p = .001, d = .46) and accessing a violent extremist website (p = .001, d = .46). The perceived benefits of engagement referred to gaining knowledge/awareness, being part of a group/similar people, and fighting the enemy/for a cause. The drawbacks referred to being exposed to negative material and emotions, having violent/criminal beliefs and behaviors, and getting in trouble with the law. The perceived benefits of disengagement referred to no longer committing illegal acts, and regaining independence/not being manipulated. The drawbacks referred to exposing oneself to harm and reprisal. These findings provide an insight into how male youth think about (dis)engagement in violent extremism, and can inform future quantitative research designed to explain and predict (dis)engagement in violent extremism. Eventually, such research may inform the development of evidence-based prevention and intervention strategies.

Deep Play. Rationality in the Life World with Special Reference to Sailing

ERIC Educational Resources Information Center

Goold, Patrick

2014-01-01

In an essay on the rationality of play, the author characterizes rationality by the three distinct demands it makes on the individual--demands for autonomy, solidarity, and integrity. He develops each of these as they apply to the sport of sailing, using the example of two deep-ocean expeditions to arrive at a concept of deep play he sees as one…

Kahenman and Tversky's Research on Heuristics and Its Application to Junior Athletic Development and the College Recruiting Process

ERIC Educational Resources Information Center

Ryan, Brendan M.

2017-01-01

This paper will apply the work of Amos Tversky and Daniel Kahneman in Prospect theory to the college recruiting process. Prospect theory challenges one of the fundamental ideas of Economics; humans are rational creatures and make rational decisions. The theory demonstrates that in fact, often humans do not make rational decisions and are instead…

Greening Transportation and Parking at University of Coimbra

ERIC Educational Resources Information Center

Cruz, Luís; Barata, Eduardo; Ferreira, João-Pedro; Freire, Fausto

2017-01-01

Purpose: This paper aims to explore the potential contribution of integrated traffic and parking management strategies to ensure more rational use of available parking spaces and to reduce fuel consumption and greenhouse gas emissions by commuters traveling to the University of Coimbra (UC) main campus. Design/methodology/approach: An integrated…

The Potential Unity of Critical Thinking and Values Analysis.

ERIC Educational Resources Information Center

Browne, M. Neil

Metaphorically, the head and the heart represent different decision-making strategies. The disjunction between these two cultures is both sharp and unnecessary. The conflict between rationality and emotion is much broader than the tension between critical thinking and values analysis, but the assumptions responsible for the mutual awkwardness of…

Demystifying Organizational Transformation: A Poetical Look at "Tomorrow's Schools".

ERIC Educational Resources Information Center

Mitchell, Brad; Varner, Donna

It is widely assumed that empowerment represents the organizational transformation strategy to help schools fulfill a broad array of announced goals, such as academic excellence, economic prosperity, military security, and social equity. This paper directs a demystifying light on the rhetoric and rationality of organizational transformation theory…

Beyond Decision Making: Cultural Ideology as Heuristic Paradigmatic Models.

ERIC Educational Resources Information Center

Whitley, L. Darrell

A paradigmatic model of cultural ideology provides a context for understanding the relationship between decision-making and personal and cultural rationality. Cultural rules or heuristics exist which indicate that many decisions can be made on the basis of established strategy rather than continual analytical calculations. When an optimal solution…

Strategies for Energy Conservation

ERIC Educational Resources Information Center

Rudd, Nancy M.; Longstreth, Molly

1978-01-01

Focusing on conservation in the residential area, the author describes five ways in which conservation can be encouraged or enforced: (1) higher prices, changed pricing structures, and/or taxes on energy to discourage use; (2) consumer education; (3) tax incentives and subsidies to promote installation of energy-saving equipment; (4) rationing;…

Teaching Cognitive-Behavioral Therapy to Undergraduate Psychology Students

ERIC Educational Resources Information Center

Ryan, Tracey Ellen; Blau, Shawn; Grozeva, Dima

2011-01-01

This article describes an experimental undergraduate psychology course that ran for two semesters during the 2009 academic year at a private, urban university in the United States. Students learned the techniques and strategies of cognitive behavioral therapy (CBT) and rational emotive behavior therapy (REBT) with a focus on the practical elements…

Mrs. Miggins in the Classroom.

ERIC Educational Resources Information Center

Barnes, Rob

2000-01-01

A therapeutic board game was devised in order to generate discussion and to dispute irrational thinking in 10 children (age 10) with behavior problems. The pupils responded positively to rational-emotive behavior therapy, and teachers found that the cards used in the game provided a framework for discussion and self-help strategies. (Contains…

The Others: Equitable Access, International Students, and the Community College

ERIC Educational Resources Information Center

Viggiano, Tiffany; López Damián, Ariadna I.; Morales Vázquez, Evelyn; Levin, John S.

2018-01-01

This qualitative investigation explains the ways in which community college decision makers justify the inclusion of international students at three community colleges in the United States. We identify and explain the ways in which decision makers rationalize institutional policy--particularly recruitment strategies and motivations--related to…

Academe Sings the Blues

ERIC Educational Resources Information Center

Wood, Robert

1975-01-01

Lack of an overall strategy for change, hostile political and social environment, and a mood of hesitancy to defend themselves, have contributed to the current problems of higher education. New directions for the future are proposed which include rational decision making based upon how the university fits the purposes and problems of the times.…

Rational Design of Improved Pharmabiotics

PubMed Central

Sleator, Roy D.; Hill, Colin

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. PMID:19753318

Rational design of improved pharmabiotics.

PubMed

Sleator, Roy D; Hill, Colin

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.

Feelings of Loss in Response to Divorce: Assessment and Intervention.

ERIC Educational Resources Information Center

Huber, Charles H.

1983-01-01

Presents a cognitively based model, founded on rational emotive therapy, as a basis for assessment and intervention strategies for assisting individuals to cope with feelings of loss in response to divorce. The model is seen as a four-pane window through which persons might see their divorce. (Author/JAC)

A One-Pot Tandem Strategy in Catalytic Asymmetric Vinylogous Aldol Reaction of Homoallylic Alcohols.

PubMed

Hou, Xufeng; Jing, Zhenzhong; Bai, Xiangbin; Jiang, Zhiyong

2016-06-27

Reported is a rationally-designed one-pot sequential strategy that allows homoallylic alcohols to be employed in a catalytic, asymmetric, direct vinylogous aldol reaction with a series of activated acyclic ketones, including trifluoromethyl ketones, γ-ketoesters, and α-keto phosphonates, in high yields (up to 95%) with excellent regio- and enantio-selectivity (up to 99% ee). This modular combination, including Jones oxidation and asymmetric organocatalysis, has satisfactory compatibility and reliability even at a 20 mmol scale, albeit without intermediary purification.

Machine learning in the rational design of antimicrobial peptides.

PubMed

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

2014-01-01

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

Neural basis of quasi-rational decision making.

PubMed

Lee, Daeyeol

2006-04-01

Standard economic theories conceive homo economicus as a rational decision maker capable of maximizing utility. In reality, however, people tend to approximate optimal decision-making strategies through a collection of heuristic routines. Some of these routines are driven by emotional processes, and others are adjusted iteratively through experience. In addition, routines specialized for social decision making, such as inference about the mental states of other decision makers, might share their origins and neural mechanisms with the ability to simulate or imagine outcomes expected from alternative actions that an individual can take. A recent surge of collaborations across economics, psychology and neuroscience has provided new insights into how such multiple elements of decision making interact in the brain.

Distributed Optimization

NASA Technical Reports Server (NTRS)

Macready, William; Wolpert, David

2005-01-01

We demonstrate a new framework for analyzing and controlling distributed systems, by solving constrained optimization problems with an algorithm based on that framework. The framework is ar. information-theoretic extension of conventional full-rationality game theory to allow bounded rational agents. The associated optimization algorithm is a game in which agents control the variables of the optimization problem. They do this by jointly minimizing a Lagrangian of (the probability distribution of) their joint state. The updating of the Lagrange parameters in that Lagrangian is a form of automated annealing, one that focuses the multi-agent system on the optimal pure strategy. We present computer experiments for the k-sat constraint satisfaction problem and for unconstrained minimization of NK functions.

Humanizing the use of technology in education: A re-examination

NASA Astrophysics Data System (ADS)

Murphy, John W.

1986-06-01

Educators are currently attempting to integrate computers into the classroom, in order to humanize their use. The strategies that have been adopted, however, are primarily logistical and ignore the philosophy that underpins this technology. It is argued in this paper that educational technology will not be humanized until it is understood to be sustained by a philosophy other than technological rationality, and thus is provided with a human base. The `life-world' ( Lebenswelt) is identified as a proper foundation for technology, because technological rationality is illustrated to be a modality of human expression. When this is the case, technology is placed in the service of humankind, for it cannot be conceived as the genesis of personal freedom.

The Role and Mechanism of Epithelial-to-Mesenchymal Transition in Prostate Cancer Progression

PubMed Central

Lo, U-Ging; Lee, Cheng-Fan; Lee, Ming-Shyue; Hsieh, Jer-Tsong

2017-01-01

In prostate cancer (PCa), similar to many other cancers, distant organ metastasis symbolizes the beginning of the end disease, which eventually leads to cancer death. Many mechanisms have been identified in this process that can be rationalized into targeted therapy. Among them, epithelial-to-mesenchymal transition (EMT) is originally characterized as a critical step for cell trans-differentiation during embryo development and now recognized in promoting cancer cells invasiveness because of high mobility and migratory abilities of mesenchymal cells once converted from carcinoma cells. Nevertheless, the underlying pathways leading to EMT appear to be very diverse in different cancer types, which certainly represent a challenge for developing effective intervention. In this article, we have carefully reviewed the key factors involved in EMT of PCa with clinical correlation in hope to facilitate the development of new therapeutic strategy that is expected to reduce the disease mortality. PMID:28973968

Development of Chengdu and sustainable utilization of the ancient Dujiangyan Water-Conservancy Project

NASA Astrophysics Data System (ADS)

Huang, X.; You, J.; Yang, P.; Chai, X.

2015-05-01

The Dujiangyan Water-Conservancy Project is a great water irrigation works in Chinese cultural history, which led the Min River water to the vast Chengdu Plain, and created fertile and pretty "land of abundance". Now Chengdu is facing increased water demand stress due mainly to rapid urbanization. This paper first analyses the available water resources of Chengdu based on historical hydrological data from 1964 to 2008. The results show that the average annual water resources were 8.9 billion m3 in 1986 and 7.9 billion m3 in 2008 under various environmental conditions. The future tendency of water demand in city development planning is predicted by the Policy Dialogue Model (PODIUM). Finally, the strategies for water resources exploitation accompanying the sustainable development pattern are studied. The result illustrates that rational and careful management are required to balance the gap between water supply and demand

Diketopyrrolopyrrole-based carbon dots for photodynamic therapy.

PubMed

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

2018-06-01

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