Socially Coherent Negotiation for Cooperative Multiagent Systems

DTIC Science & Technology

2008-07-16

of altruism by substituting the preferences of others for one’s own. • It is assumed that each member will...approximation) — it is not a species of bounded rationality. (c) It naturally extends to the multi-agent case, thereby providing a natural frame- work...are mass functions, permits a natural way to aggregate the preference orderings of the individuals to form a group preference ordering. As is well

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.

Bounded Rationality, Emotions and Older Adult Decision Making: Not so Fast and yet so Frugal

ERIC Educational Resources Information Center

Hanoch, Yaniv; Wood, Stacey; Rice, Thomas

2007-01-01

Herbert Simon's work on bounded rationality has had little impact on researchers studying older adults' decision making. This omission is surprising, as human constraints on computation and memory are exacerbated in older adults. The study of older adults' decision-making processes could benefit from employing a bounded rationality perspective,…

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)…

Bounded rationality alters the dynamics of paediatric immunization acceptance.

PubMed

Oraby, Tamer; Bauch, Chris T

2015-06-02

Interactions between disease dynamics and vaccinating behavior have been explored in many coupled behavior-disease models. Cognitive effects such as risk perception, framing, and subjective probabilities of adverse events can be important determinants of the vaccinating behaviour, and represent departures from the pure "rational" decision model that are often described as "bounded rationality". However, the impact of such cognitive effects in the context of paediatric infectious disease vaccines has received relatively little attention. Here, we develop a disease-behavior model that accounts for bounded rationality through prospect theory. We analyze the model and compare its predictions to a reduced model that lacks bounded rationality. We find that, in general, introducing bounded rationality increases the dynamical richness of the model and makes it harder to eliminate a paediatric infectious disease. In contrast, in other cases, a low cost, highly efficacious vaccine can be refused, even when the rational decision model predicts acceptance. Injunctive social norms can prevent vaccine refusal, if vaccine acceptance is sufficiently high in the beginning of the vaccination campaign. Cognitive processes can have major impacts on the predictions of behaviour-disease models, and further study of such processes in the context of vaccination is thus warranted.

Finding Bounded Rational Equilibria. Part 1; Iterative Focusing

NASA Technical Reports Server (NTRS)

Wolpert, David H.

2004-01-01

A long-running difficulty with conventional game theory has been how to modify it to accommodate the bounded rationality characterizing all real-world players. A recurring issue in statistical physics is how best to approximate joint probability distributions with decoupled (and therefore far more tractable) distributions. It has recently been shown that the same information theoretic mathematical structure, known as Probability Collectives (PC) underlies both issues. This relationship between statistical physics and game theory allows techniques and insights from the one field to be applied to the other. In particular, PC provides a formal model-independent definition of the degree of rationality of a player and of bounded rationality equilibria. This pair of papers extends previous work on PC by introducing new computational approaches to effectively find bounded rationality equilibria of common-interest (team) games.

Playing Games and Making Decisions with Complex State Spaces, Resource-Bounded Agents, and Unforeseen Contingencies

DTIC Science & Technology

2012-01-20

t) = ∑ ~a∈A(σ1(t1)(a1) × . . . × σm(tm)(am))ui(~t,~a). Player i’s expected utility if ~σ is played, denoted Ui(~σ), is then just EPr [u ~σ i ] = ∑ ~t∈T...well-known Traveler’s Dilemma (K. Basu, The traveler’s dilemma: paradoxes of rationality in game theory, American Economic Review 84:2, 1994, pp. 391

Speculative and Hedging Interaction Model in Oil and U.S. Dollar Markets—Phase Transition

NASA Astrophysics Data System (ADS)

Campbell, Michael; Carfì, David

2018-01-01

We show that there is a phase transition in the bounded rational Carfì-Musolino model, and the possibility of a market crash. This model has two types of operators: a real economic subject (Air) and one or more investment banks (Bank). It also has two markets: oil spot market and US dollar futures. Bank agents react to Air and equilibrate much more quickly than Air. Thus Air is an acting external agent due to its longer-term investing, whereas the action of the banks equilibrates before Air makes its next transaction. This model constitutes a potential game, and agents crowd their preferences into one of the markets at a critical temperature when air makes no purchases of oil futures.

Finding Bounded Rational Equilibria. Part 2; Alternative Lagrangians and Uncountable Move Spaces

NASA Technical Reports Server (NTRS)

Wolpert, David H.

2004-01-01

A long-running difficulty with conventional game theory has been how to modify it to accommodate the bounded rationality characterizing all real-world players. A recurring issue in statistical physics is how best to approximate joint probability distributions with decoupled (and therefore far more tractable) distributions. It has recently been shown that the same information theoretic mathematical structure, known as Probability Collectives (PC) underlies both issues. This relationship between statistical physics and game theory allows techniques and insights &om the one field to be applied to the other. In particular, PC provides a formal model-independent definition of the degree of rationality of a player and of bounded rationality equilibria. This pair of papers extends previous work on PC by introducing new computational approaches to effectively find bounded rationality equilibria of common-interest (team) games.

Decision theory with resource-bounded agents.

PubMed

Halpern, Joseph Y; Pass, Rafael; Seeman, Lior

2014-04-01

There have been two major lines of research aimed at capturing resource-bounded players in game theory. The first, initiated by Rubinstein (), charges an agent for doing costly computation; the second, initiated by Neyman (), does not charge for computation, but limits the computation that agents can do, typically by modeling agents as finite automata. We review recent work on applying both approaches in the context of decision theory. For the first approach, we take the objects of choice in a decision problem to be Turing machines, and charge players for the "complexity" of the Turing machine chosen (e.g., its running time). This approach can be used to explain well-known phenomena like first-impression-matters biases (i.e., people tend to put more weight on evidence they hear early on) and belief polarization (two people with different prior beliefs, hearing the same evidence, can end up with diametrically opposed conclusions) as the outcomes of quite rational decisions. For the second approach, we model people as finite automata, and provide a simple algorithm that, on a problem that captures a number of settings of interest, provably performs optimally as the number of states in the automaton increases. Copyright © 2014 Cognitive Science Society, Inc.

New leads in speculative behavior

NASA Astrophysics Data System (ADS)

Kindler, A.; Bourgeois-Gironde, S.; Lefebvre, G.; Solomon, S.

2017-02-01

The Kiyotaki and Wright (1989) (henceforth KW) model of money emergence as a medium of exchange has been studied from various perspectives in recent papers. In the present work we propose a minimalistic model for the behavior of agents in the KW framework, which may either reproduce the theoretical predictions of Kiyotaki and Wright (1989) on the emerging Nash equilibria, or (less closely) the empirical results of Brown (1996), Duffy and Ochs (1999) and our own, introduced in a first part of the present paper. The main import is the systematic computer scanning of speculative monetary equilibria under drastic bounded rationality of agents, based on behavior previously observed in the lab.

Matching games with partial information

NASA Astrophysics Data System (ADS)

Laureti, Paolo; Zhang, Yi-Cheng

2003-06-01

We analyze different ways of pairing agents in a bipartite matching problem, with regard to its scaling properties and to the distribution of individual “satisfactions”. Then we explore the role of partial information and bounded rationality in a generalized Marriage Problem, comparing the benefits obtained by self-searching and by a matchmaker. Finally we propose a modified matching game intended to mimic the way consumers’ information makes firms to enhance the quality of their products in a competitive market.

Adaptive, Distributed Control of Constrained Multi-Agent Systems

NASA Technical Reports Server (NTRS)

Bieniawski, Stefan; Wolpert, David H.

2004-01-01

Product Distribution (PO) theory was recently developed as a broad framework for analyzing and optimizing distributed systems. Here we demonstrate its use for adaptive distributed control of Multi-Agent Systems (MASS), i.e., for distributed stochastic optimization using MAS s. First we review one motivation of PD theory, as the information-theoretic extension of conventional full-rationality game theory to the case of bounded rational agents. In this extension the equilibrium of the game is the optimizer of a Lagrangian of the (Probability dist&&on on the joint state of the agents. When the game in question is a team game with constraints, that equilibrium optimizes the expected value of the team game utility, subject to those constraints. One common way to find that equilibrium is to have each agent run a Reinforcement Learning (E) algorithm. PD theory reveals this to be a particular type of search algorithm for minimizing the Lagrangian. Typically that algorithm i s quite inefficient. A more principled alternative is to use a variant of Newton's method to minimize the Lagrangian. Here we compare this alternative to RL-based search in three sets of computer experiments. These are the N Queen s problem and bin-packing problem from the optimization literature, and the Bar problem from the distributed RL literature. Our results confirm that the PD-theory-based approach outperforms the RL-based scheme in all three domains.

Bounded rationality, retaliation, and the spread of urban violence.

PubMed

Jacobs, Bruce A; Wright, Richard

2010-10-01

Drawing from in-depth interviews with 52 active street criminals, this article examines the grounded theoretic implications of bounded rationality for retaliatory street violence. The bounds on rationality that this article explores are anger, uncertainty, and time pressure. These bounds create imperfections in the retaliatory decision-making process that, in turn, cause asymmetries in the way that reprisal is enacted. Two asymmetries are operative in this regard: strike intensity and target choice. Anger produces asymmetries of both types. Uncertainty and time pressure produce only target-choice asymmetry. All three modalities cause retaliation to be redirected. Redirection promotes the spread of urban violence through conflict spirals.

Bounded rationality alters the dynamics of paediatric immunization acceptance

PubMed Central

Oraby, Tamer; Bauch, Chris T.

2015-01-01

Interactions between disease dynamics and vaccinating behavior have been explored in many coupled behavior-disease models. Cognitive effects such as risk perception, framing, and subjective probabilities of adverse events can be important determinants of the vaccinating behaviour, and represent departures from the pure “rational” decision model that are often described as “bounded rationality”. However, the impact of such cognitive effects in the context of paediatric infectious disease vaccines has received relatively little attention. Here, we develop a disease-behavior model that accounts for bounded rationality through prospect theory. We analyze the model and compare its predictions to a reduced model that lacks bounded rationality. We find that, in general, introducing bounded rationality increases the dynamical richness of the model and makes it harder to eliminate a paediatric infectious disease. In contrast, in other cases, a low cost, highly efficacious vaccine can be refused, even when the rational decision model predicts acceptance. Injunctive social norms can prevent vaccine refusal, if vaccine acceptance is sufficiently high in the beginning of the vaccination campaign. Cognitive processes can have major impacts on the predictions of behaviour-disease models, and further study of such processes in the context of vaccination is thus warranted. PMID:26035413

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.

Combining human and machine intelligence to derive agents' behavioral rules for groundwater irrigation

NASA Astrophysics Data System (ADS)

Hu, Yao; Quinn, Christopher J.; Cai, Ximing; Garfinkle, Noah W.

2017-11-01

For agent-based modeling, the major challenges in deriving agents' behavioral rules arise from agents' bounded rationality and data scarcity. This study proposes a "gray box" approach to address the challenge by incorporating expert domain knowledge (i.e., human intelligence) with machine learning techniques (i.e., machine intelligence). Specifically, we propose using directed information graph (DIG), boosted regression trees (BRT), and domain knowledge to infer causal factors and identify behavioral rules from data. A case study is conducted to investigate farmers' pumping behavior in the Midwest, U.S.A. Results show that four factors identified by the DIG algorithm- corn price, underlying groundwater level, monthly mean temperature and precipitation- have main causal influences on agents' decisions on monthly groundwater irrigation depth. The agent-based model is then developed based on the behavioral rules represented by three DIGs and modeled by BRTs, and coupled with a physically-based groundwater model to investigate the impacts of agents' pumping behavior on the underlying groundwater system in the context of coupled human and environmental systems.

Computational rationality: linking mechanism and behavior through bounded utility maximization.

PubMed

Lewis, Richard L; Howes, Andrew; Singh, Satinder

2014-04-01

We propose a framework for including information-processing bounds in rational analyses. It is an application of bounded optimality (Russell & Subramanian, 1995) to the challenges of developing theories of mechanism and behavior. The framework is based on the idea that behaviors are generated by cognitive mechanisms that are adapted to the structure of not only the environment but also the mind and brain itself. We call the framework computational rationality to emphasize the incorporation of computational mechanism into the definition of rational action. Theories are specified as optimal program problems, defined by an adaptation environment, a bounded machine, and a utility function. Such theories yield different classes of explanation, depending on the extent to which they emphasize adaptation to bounds, and adaptation to some ecology that differs from the immediate local environment. We illustrate this variation with examples from three domains: visual attention in a linguistic task, manual response ordering, and reasoning. We explore the relation of this framework to existing "levels" approaches to explanation, and to other optimality-based modeling approaches. Copyright © 2014 Cognitive Science Society, Inc.

Are transaction taxes a cause of financial instability?

NASA Astrophysics Data System (ADS)

Fontini, Fulvio; Sartori, Elena; Tolotti, Marco

2016-05-01

We analyze a stylized market where N boundedly rational agents may decide to trade or not a share of a risky asset at subsequent trading dates. Agents' payoff depends on returns, which are endogenously determined taking into account observed and forecasted demand and an exogenous transaction tax. We study the time evolutions of demand, returns and market activity. We show that the introduction of a transaction tax generally helps in reducing variability of returns and market activity. On the other hand, there are market conditions under which a low taxation may lead the market into a very unstable phase characterized by the fluctuation of the fundamentals around two different regimes; indeed, under these circumstances, heteroscedasticity of time series is detected and statistically analyzed.

Emergence of scale-free characteristics in socio-ecological systems with bounded rationality

PubMed Central

Kasthurirathna, Dharshana; Piraveenan, Mahendra

2015-01-01

Socio–ecological systems are increasingly modelled by games played on complex networks. While the concept of Nash equilibrium assumes perfect rationality, in reality players display heterogeneous bounded rationality. Here we present a topological model of bounded rationality in socio-ecological systems, using the rationality parameter of the Quantal Response Equilibrium. We argue that system rationality could be measured by the average Kullback–-Leibler divergence between Nash and Quantal Response Equilibria, and that the convergence towards Nash equilibria on average corresponds to increased system rationality. Using this model, we show that when a randomly connected socio-ecological system is topologically optimised to converge towards Nash equilibria, scale-free and small world features emerge. Therefore, optimising system rationality is an evolutionary reason for the emergence of scale-free and small-world features in socio-ecological systems. Further, we show that in games where multiple equilibria are possible, the correlation between the scale-freeness of the system and the fraction of links with multiple equilibria goes through a rapid transition when the average system rationality increases. Our results explain the influence of the topological structure of socio–ecological systems in shaping their collective cognitive behaviour, and provide an explanation for the prevalence of scale-free and small-world characteristics in such systems. PMID:26065713

Emergence of scale-free characteristics in socio-ecological systems with bounded rationality.

PubMed

Kasthurirathna, Dharshana; Piraveenan, Mahendra

2015-06-11

Socio-ecological systems are increasingly modelled by games played on complex networks. While the concept of Nash equilibrium assumes perfect rationality, in reality players display heterogeneous bounded rationality. Here we present a topological model of bounded rationality in socio-ecological systems, using the rationality parameter of the Quantal Response Equilibrium. We argue that system rationality could be measured by the average Kullback--Leibler divergence between Nash and Quantal Response Equilibria, and that the convergence towards Nash equilibria on average corresponds to increased system rationality. Using this model, we show that when a randomly connected socio-ecological system is topologically optimised to converge towards Nash equilibria, scale-free and small world features emerge. Therefore, optimising system rationality is an evolutionary reason for the emergence of scale-free and small-world features in socio-ecological systems. Further, we show that in games where multiple equilibria are possible, the correlation between the scale-freeness of the system and the fraction of links with multiple equilibria goes through a rapid transition when the average system rationality increases. Our results explain the influence of the topological structure of socio-ecological systems in shaping their collective cognitive behaviour, and provide an explanation for the prevalence of scale-free and small-world characteristics in such systems.

Issues of Dynamic Coalition Formation Among Rational Agents

DTIC Science & Technology

2002-04-01

approaches of forming stable coalitions among rational agents. Issues and problems of dynamic coalition environments are discussed in section 3 while...2.2. 2.1.2 Coalition Algorithm, Coalition Formation Environment and Model Rational agents which are involved in a co-operative game (A,v) are...publicly available simulation environment for coalition formation among rational information agents based on selected classic coalition theories is, for

The Evolution of ICT Markets: An Agent-Based Model on Complex Networks

NASA Astrophysics Data System (ADS)

Zhao, Liangjie; Wu, Bangtao; Chen, Zhong; Li, Li

Information and communication technology (ICT) products exhibit positive network effects.The dynamic process of ICT markets evolution has two intrinsic characteristics: (1) customers are influenced by each others’ purchasing decision; (2) customers are intelligent agents with bounded rationality.Guided by complex systems theory, we construct an agent-based model and simulate on complex networks to examine how the evolution can arise from the interaction of customers, which occur when they make expectations about the future installed base of a product by the fraction of neighbors who are using the same product in his personal network.We demonstrate that network effects play an important role in the evolution of markets share, which make even an inferior product can dominate the whole market.We also find that the intensity of customers’ communication can influence whether the best initial strategy for firms is to improve product quality or expand their installed base.

Information Theory - The Bridge Connecting Bounded Rational Game Theory and Statistical Physics

NASA Technical Reports Server (NTRS)

Wolpert, David H.

2005-01-01

A long-running difficulty with conventional game theory has been how to modify it to accommodate the bounded rationality of all red-world players. A recurring issue in statistical physics is how best to approximate joint probability distributions with decoupled (and therefore far more tractable) distributions. This paper shows that the same information theoretic mathematical structure, known as Product Distribution (PD) theory, addresses both issues. In this, PD theory not only provides a principle formulation of bounded rationality and a set of new types of mean field theory in statistical physics; it also shows that those topics are fundamentally one and the same.

Deals Among Rational Agents,

DTIC Science & Technology

1985-03-01

ARD-AI57 966 DEALS AMONG RATIONAL AGENTS(U) STANFORD UNIV CA DEPT OF 1/1lit COMPUTER SCIENCE J S ROSENSCHEIN ET AL. MAR 857 STAN-CS-85-1e42 NOO039-83... Rational Agents by Jeffrey S. Rosenschemn Michael R. Genesereth Contract N00039-83-c-0136 Department of Computer Science Stanford University Stanford, CA... Rational Agents Jeffrey S. Rosenschein Michael R. Genesereth COMPUTER SCIENCE DEPARTME NT Stanford University Sta-;!ord, California 94305 A ~ ,2 TA

A Reward-Maximizing Spiking Neuron as a Bounded Rational Decision Maker.

PubMed

Leibfried, Felix; Braun, Daniel A

2015-08-01

Rate distortion theory describes how to communicate relevant information most efficiently over a channel with limited capacity. One of the many applications of rate distortion theory is bounded rational decision making, where decision makers are modeled as information channels that transform sensory input into motor output under the constraint that their channel capacity is limited. Such a bounded rational decision maker can be thought to optimize an objective function that trades off the decision maker's utility or cumulative reward against the information processing cost measured by the mutual information between sensory input and motor output. In this study, we interpret a spiking neuron as a bounded rational decision maker that aims to maximize its expected reward under the computational constraint that the mutual information between the neuron's input and output is upper bounded. This abstract computational constraint translates into a penalization of the deviation between the neuron's instantaneous and average firing behavior. We derive a synaptic weight update rule for such a rate distortion optimizing neuron and show in simulations that the neuron efficiently extracts reward-relevant information from the input by trading off its synaptic strengths against the collected reward.

Reference Service and Bounded Rationality: Helping Students with Research.

ERIC Educational Resources Information Center

Chu, Felix T.

1994-01-01

In university libraries, reference librarians often get ambiguous questions to which they try to give appropriate answers. Because of limitations on resources, time, and mental capability for information processing, the decision-making process involved in answering reference questions becomes bounded by the rationality of these constraints.…

Bounded Rationality and Satisficing in Young People's Web-Based Decision Making.

ERIC Educational Resources Information Center

Agosto, Denise E.

2002-01-01

Investigated behavioral decision-making theories of bounded rationality and satisficing in relation to young people's decision making in the World Wide Web and considered the role of personal preferences. Results of this study of ninth- and tenth-grade females consider time constraints, information overload, physical constraints, reduction…

Robust consensus algorithm for multi-agent systems with exogenous disturbances under convergence conditions

NASA Astrophysics Data System (ADS)

Jiang, Yulian; Liu, Jianchang; Tan, Shubin; Ming, Pingsong

2014-09-01

In this paper, a robust consensus algorithm is developed and sufficient conditions for convergence to consensus are proposed for a multi-agent system (MAS) with exogenous disturbances subject to partial information. By utilizing H∞ robust control, differential game theory and a design-based approach, the consensus problem of the MAS with exogenous bounded interference is resolved and the disturbances are restrained, simultaneously. Attention is focused on designing an H∞ robust controller (the robust consensus algorithm) based on minimisation of our proposed rational and individual cost functions according to goals of the MAS. Furthermore, sufficient conditions for convergence of the robust consensus algorithm are given. An example is employed to demonstrate that our results are effective and more capable to restrain exogenous disturbances than the existing literature.

Dynamic route and departure time choice model based on self-adaptive reference point and reinforcement learning

NASA Astrophysics Data System (ADS)

Li, Xue-yan; Li, Xue-mei; Yang, Lingrun; Li, Jing

2018-07-01

Most of the previous studies on dynamic traffic assignment are based on traditional analytical framework, for instance, the idea of Dynamic User Equilibrium has been widely used in depicting both the route choice and the departure time choice. However, some recent studies have demonstrated that the dynamic traffic flow assignment largely depends on travelers' rationality degree, travelers' heterogeneity and what the traffic information the travelers have. In this paper, we develop a new self-adaptive multi agent model to depict travelers' behavior in Dynamic Traffic Assignment. We use Cumulative Prospect Theory with heterogeneous reference points to illustrate travelers' bounded rationality. We use reinforcement-learning model to depict travelers' route and departure time choosing behavior under the condition of imperfect information. We design the evolution rule of travelers' expected arrival time and the algorithm of traffic flow assignment. Compared with the traditional model, the self-adaptive multi agent model we proposed in this paper can effectively help travelers avoid the rush hour. Finally, we report and analyze the effect of travelers' group behavior on the transportation system, and give some insights into the relation between travelers' group behavior and the performance of transportation system.

The anchoring bias reflects rational use of cognitive resources.

PubMed

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

2018-02-01

Cognitive biases, such as the anchoring bias, pose a serious challenge to rational accounts of human cognition. We investigate whether rational theories can meet this challenge by taking into account the mind's bounded cognitive resources. We asked what reasoning under uncertainty would look like if people made rational use of their finite time and limited cognitive resources. To answer this question, we applied a mathematical theory of bounded rationality to the problem of numerical estimation. Our analysis led to a rational process model that can be interpreted in terms of anchoring-and-adjustment. This model provided a unifying explanation for ten anchoring phenomena including the differential effect of accuracy motivation on the bias towards provided versus self-generated anchors. Our results illustrate the potential of resource-rational analysis to provide formal theories that can unify a wide range of empirical results and reconcile the impressive capacities of the human mind with its apparently irrational cognitive biases.

Local stability condition of the equilibrium of an oligopoly market with bounded rationality adjustment

NASA Astrophysics Data System (ADS)

Ibrahim, Adyda; Saaban, Azizan; Zaibidi, Nerda Zura

2017-11-01

This paper considers an n-firm oligopoly market where each firm produces a single homogenous product under a constant unit cost. Nonlinearity is introduced into the model of this oligopoly market by assuming the market has an isoelastic demand function. Furthermore, instead of the usual assumption of perfectly rational firms, they are assumed to be boundedly rational in adjusting their outputs at each period. The equilibrium of this n discrete dimensional system is obtained and its local stability is calculated.

Modeling the stylized facts in finance through simple nonlinear adaptive systems

PubMed Central

Hommes, Cars H.

2002-01-01

Recent work on adaptive systems for modeling financial markets is discussed. Financial markets are viewed as evolutionary systems between different, competing trading strategies. Agents are boundedly rational in the sense that they tend to follow strategies that have performed well, according to realized profits or accumulated wealth, in the recent past. Simple technical trading rules may survive evolutionary competition in a heterogeneous world where prices and beliefs co-evolve over time. Evolutionary models can explain important stylized facts, such as fat tails, clustered volatility, and long memory, of real financial series. PMID:12011401

Economic modelling with low-cognition agents

NASA Astrophysics Data System (ADS)

Ormerod, Paul

2006-10-01

The standard socio-economic model (SSSM) postulates very considerable cognitive powers on the part of its agents. They are able to gather all relevant information in any given situation, and to take the optimal decision on the basis of it, given their tastes and preferences. This behavioural rule is postulated to be universal. The concept of bounded rationality relaxes this somewhat, by permitting agents to have access to only limited amounts of information. But agents still optimise subject to their information set and tastes. Empirical work in economics over the past 20 years or so has shown that in general these behavioural postulates lack empirical validity. Instead, agents appear to have limited ability to gather information, and use simple rules of thumb to process the information which they have in order to take decisions. Building theoretical models on these realistic foundations which give better accounts of empirical phenomena than does the SSSM is an important challenge to both economists and econophysicists. Considerable progress has already been made in a short space of time, and examples are given in this paper.

Simon and the Sirens: A Commentary.

PubMed

Daston, Lorraine

2015-09-01

Even in its extended usage, the concept of bounded rationality bears the birthmark of its origins in economics. First and most obviously, it is about seeking the most efficient (not necessarily the best) means toward a given end, whether that is curing patients or proving theorems. Second, the means are whittled down to the most parsimonious possible, not only acknowledging cognitive limitations but actually imposing them, whether in the form of Morgan's canon, Methodist agnosticism about causes, or Entscheidungsproblem-like restrictions on the acceptable formulation of mathematical proofs. Third, these parsimonious restrictions all tend to minimize the role of reasonable deliberation in rationality, albeit in different ways. As an object of inquiry for the history of science, bounded rationality has great promise. But as a model of the history of science, as one long exercise in bounded rationality, its utility may apply more to future than past science.

Transition in the waiting-time distribution of price-change events in a global socioeconomic system

NASA Astrophysics Data System (ADS)

Zhao, Guannan; McDonald, Mark; Fenn, Dan; Williams, Stacy; Johnson, Nicholas; Johnson, Neil F.

2013-12-01

The goal of developing a firmer theoretical understanding of inhomogeneous temporal processes-in particular, the waiting times in some collective dynamical system-is attracting significant interest among physicists. Quantifying the deviations between the waiting-time distribution and the distribution generated by a random process may help unravel the feedback mechanisms that drive the underlying dynamics. We analyze the waiting-time distributions of high-frequency foreign exchange data for the best executable bid-ask prices across all major currencies. We find that the lognormal distribution yields a good overall fit for the waiting-time distribution between currency rate changes if both short and long waiting times are included. If we restrict our study to long waiting times, each currency pair’s distribution is consistent with a power-law tail with exponent near to 3.5. However, for short waiting times, the overall distribution resembles one generated by an archetypal complex systems model in which boundedly rational agents compete for limited resources. Our findings suggest that a gradual transition arises in trading behavior between a fast regime in which traders act in a boundedly rational way and a slower one in which traders’ decisions are driven by generic feedback mechanisms across multiple timescales and hence produce similar power-law tails irrespective of currency type.

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.

Integrating Household Risk Mitigation Behavior in Flood Risk Analysis: An Agent-Based Model Approach.

PubMed

Haer, Toon; Botzen, W J Wouter; de Moel, Hans; Aerts, Jeroen C J H

2017-10-01

Recent studies showed that climate change and socioeconomic trends are expected to increase flood risks in many regions. However, in these studies, human behavior is commonly assumed to be constant, which neglects interaction and feedback loops between human and environmental systems. This neglect of human adaptation leads to a misrepresentation of flood risk. This article presents an agent-based model that incorporates human decision making in flood risk analysis. In particular, household investments in loss-reducing measures are examined under three economic decision models: (1) expected utility theory, which is the traditional economic model of rational agents; (2) prospect theory, which takes account of bounded rationality; and (3) a prospect theory model, which accounts for changing risk perceptions and social interactions through a process of Bayesian updating. We show that neglecting human behavior in flood risk assessment studies can result in a considerable misestimation of future flood risk, which is in our case study an overestimation of a factor two. Furthermore, we show how behavior models can support flood risk analysis under different behavioral assumptions, illustrating the need to include the dynamic adaptive human behavior of, for instance, households, insurers, and governments. The method presented here provides a solid basis for exploring human behavior and the resulting flood risk with respect to low-probability/high-impact risks. © 2016 The Authors Risk Analysis published by Wiley Periodicals, Inc. on behalf of Society for Risk Analysis.

A monofunctional platinum(II)-based anticancer agent from a salicylanilide derivative: Synthesis, antiproliferative activity, and transcription inhibition.

PubMed

Wang, Beilei; Wang, Zhigang; Ai, Fujin; Tang, Wai Kin; Zhu, Guangyu

2015-01-01

Cationic monofunctional platinum(II)-based anticancer agents with a general formula of cis-[Pt(NH3)2(N-donor)Cl](+) have recently drawn significant attention due to their unique mode of action, distinctive anticancer spectrum, and promising antitumor activity both in vitro and in vivo. Understanding the mechanism of action of novel monofunctional platinum compounds through rational drug design will aid in the further development of active agents. In this study, we synthesized and evaluated a monofunctional platinum-based anticancer agent SA-Pt containing a bulky salicylanilide moiety. The antiproliferative activity of SA-Pt was close to that of cisplatin. Mechanism studies revealed that SA-Pt entered HeLa cells more efficiently than cisplatin, blocked the cell cycle at the S-phase, and induced apoptosis. The compound bound to DNA as effectively as cisplatin, but did not block RNA polymerase II-mediated transcription as strongly as cisplatin, indicating that once the compound formed Pt-DNA lesions, the salicylanilide group was more easily recognized and removed. This study not only enriches the family of monofunctional platinum-based anticancer agents but also guides the design of more potent monofunctional platinum complexes. Copyright © 2014 Elsevier Inc. All rights reserved.

Assessment: Give Me a Place to Stand, and I Will Move the Earth

DTIC Science & Technology

2012-06-01

Theory , and Policy Keywords: C2 agility, bounded rationality, heuristics, uncertainty, assessment Authors: Erik Bjurström Mälardalen...of making decisions. Although the notion of bounded rationality and its associated theory rendered Herbert Simon the 1978 Nobel prize in economics...future and represents a more structuralistic approach. While making predictions about the future is often necessary it is not feasible as a general

Market mechanism based on the endogenous changing of game types such as Minority-Majority games

NASA Astrophysics Data System (ADS)

Ahn, Sanghyun; Lim, Gyuchang; Kim, Sooyong; Kim, Kyungsik

2010-03-01

In many social and biological systems agents simultaneously and adaptively compete for limited resources, thereby altering their environment. We propose a evolution function extending Minority-Majority Games that captures the competition between agents to make money. The dynamics changes the ratio of two types of boundedly rational traders, fundamentalists and chartists with the payoff function endogenously. In the previous game theories, the best strategies are not always targeting the minority but are shifting opportunistically between the minority and the majority. And using a mixture of local bifurcation theory and numerical methods, there are possible bifurcation routes to complicated asset price dynamics, chaotic attractors. Hereby we improve the thinking logic of the atoms for attaching the dynamics to the market. This working shows that removing unrealistic features of the game theories leads to models which reproduce a behavior close to what is observed in real markets.

Cognitive Architectures and Rational Analysis: Comment

DTIC Science & Technology

1989-03-17

These last three are assumptions- about the structure of the task 12 Architectures and Rationality 17 March 1989 environment , and are empirically... rationality is what cognitive psychology is all about. And the study of bounded rationality is not the study of optimization in relation tc tPok environments ...one must 16 Architectures and Rationality 17 March 1989 consider both the task environment and the limits upon the adaptive Powers of the system. Only

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…

Rational Budgeting? The Stanford Case.

ERIC Educational Resources Information Center

Chaffee, Ellen Earle

The budget decision making process at Stanford University, California, from 1970 through 1979 was evaluated in relation to the allocation of general funds to 38 academic departments. Using Simon's theory of bounded rationality and an organizational level of analysis, the Stanford decision process was tested for its rationality through…

Network marketing with bounded rationality and partial information

NASA Astrophysics Data System (ADS)

Kiet, Hoang Anh Tuan; Kim, Beom Jun

2008-08-01

Network marketing has been proposed and used as a way to spread the product information to consumers through social connections. We extend the previous game model of the network marketing on a small-world tree network and propose two games: In the first model with the bounded rationality, each consumer makes purchase decision stochastically, while in the second model, consumers get only partial information due to the finite length of social connections. Via extensive numerical simulations, we find that as the rationality is enhanced not only the consumer surplus but also the firm’s profit is increased. The implication of our results is also discussed.

A Model for Determining Optimal Governance Structure in DoD Acquisition Projects in a Performance-Based Environment

DTIC Science & Technology

2010-04-30

combating market dynamism (Aldrich, 1979; Child, 1972), which is a result of evolving technology, shifting prices, or variance in product availability... principles : (1) human beings are bounded rationally, and (2), as a result of being rationally bound, will always choose to further their own self... principles to govern the relationship among the buyers and suppliers. Our conceptual model aligns the alternative governance structures derived

Approaching system equilibrium with accurate or not accurate feedback information in a two-route system

NASA Astrophysics Data System (ADS)

Zhao, Xiao-mei; Xie, Dong-fan; Li, Qi

2015-02-01

With the development of intelligent transport system, advanced information feedback strategies have been developed to reduce traffic congestion and enhance the capacity. However, previous strategies provide accurate information to travelers and our simulation results show that accurate information brings negative effects, especially in delay case. Because travelers prefer to the best condition route with accurate information, and delayed information cannot reflect current traffic condition but past. Then travelers make wrong routing decisions, causing the decrease of the capacity and the increase of oscillations and the system deviating from the equilibrium. To avoid the negative effect, bounded rationality is taken into account by introducing a boundedly rational threshold BR. When difference between two routes is less than the BR, routes have equal probability to be chosen. The bounded rationality is helpful to improve the efficiency in terms of capacity, oscillation and the gap deviating from the system equilibrium.

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.

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

PubMed

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

2015-07-01

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

Person perception and the bounded rationality of social judgment.

PubMed

Wright, J C; Dawson, V L

1988-11-01

In this article, we develop a bounded rationality view of the relation between person perception and social behavior. Two theses of this approach are that behaviors vary in their significance to observers, and that observers pursue bounded rather than global utility in forming personality impressions. Observers are expected to be sensitive to targets' overall behavioral tendencies and to the variability of their behavior across situations, but both sensitivities are bounded, being greater for behaviors that directly affect observers' outcomes. In two investigations involving extensive hourly and 6-s observations, we examined the bounded utility of people's impressions of personality, demonstrating how impression accuracy is linked to the significance of behaviors. Observers were sensitive to the organization of aggressive behaviors, but less sensitive to the organization of withdrawn behaviors, even when the consistency of those behaviors was comparable. The results clarify the relation between people's inferential shortcomings in laboratory paradigms and the bounded utility of person perception in the natural environment.

Rational Adaptation under Task and Processing Constraints: Implications for Testing Theories of Cognition and Action

ERIC Educational Resources Information Center

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

2009-01-01

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…

Dynamics of market structure driven by the degree of consumer’s rationality

NASA Astrophysics Data System (ADS)

Yanagita, Tatsuo; Onozaki, Tamotsu

2010-03-01

We study a simple model of market share dynamics with boundedly rational consumers and firms interacting with each other. As the number of consumers is large, we employ a statistical description to represent firms’ distribution of consumer share, which is characterized by a single parameter representing how rationally the mass of consumers pursue higher utility. As the boundedly rational firm does not know the shape of demand function it faces, it revises production and price so as to raise its profit with the aid of a simple reinforcement learning rule. Simulation results show that (1) three phases of market structure, i.e. the uniform share phase, the oligopolistic phase, and the monopolistic phase, appear depending upon how rational consumers are, and (2) in an oligopolistic phase, the market share distribution of firms follows Zipf’s law and the growth-rate distribution of firms follows Gibrat’s law, and (3) an oligopolistic phase is the best state of market in terms of consumers’ utility but brings the minimum profit to the firms because of severe competition based on the moderate rationality of consumers.

Application of a Genetic Algorithm and Multi Agent System to Explore Emergent Patterns of Social Rationality and a Distress-Based Model for Deceit in the Workplace

DTIC Science & Technology

2008-06-01

postponed the fulfillment of her own Masters Degree by at least 18 months so that I would have the opportunity to earn mine. She is smart , lovely...GENETIC ALGORITHM AND MULTI AGENT SYSTEM TO EXPLORE EMERGENT PATTERNS OF SOCIAL RATIONALITY AND A DISTRESS-BASED MODEL FOR DECEIT IN THE WORKPLACE...of a Genetic Algorithm and Mutli Agent System to Explore Emergent Patterns of Social Rationality and a Distress-Based Model for Deceit in the

ProgrammingRationalAgents in GOAL

NASA Astrophysics Data System (ADS)

Hindriks, Koen V.

The agent programming language GOAL is a high-level programming language to program rational agents that derive their choice of action from their beliefsand goals. The language provides the basic building blocks to design and implementrationalagents by meansofa setofprogramming constructs. These programming constructs allow and facilitate the manipulation of an agent’sbeliefs and goals and to structure its decision-making. GOAL agents are called rational because they satisfy a numberof basic rationality constraints and because they decide to perform actions to further their goals based uponareasoning scheme derived from practical reasoning. The programming concepts of belief and goal incorporated into GOAL provide the basis for this form of reasoning and are similarto their common sense counterparts used everyday to explain the actions that we perform. In addition, GOAL provides the means for agents to focus their attention on specic goals and to communicate at the knowledge level. This provides an intuitive basis for writing high-level agent programs. At the same time these concepts and programming constructs have a well-dened, formal semantics. The formal semantics provides the basis for deninga verication framework for GOAL for verifying and reasoning about GOAL agents whichis similar to some of the wellknownagent logics introduced in the literature.

Coevolution in management fashion: an agent-based model of consultant-driven innovation.

PubMed

Strang, David; David, Robert J; Akhlaghpour, Saeed

2014-07-01

The rise of management consultancy has been accompanied by increasingly marked faddish cycles in management techniques, but the mechanisms that underlie this relationship are not well understood. The authors develop a simple agent-based framework that models innovation adoption and abandonment on both the supply and demand sides. In opposition to conceptions of consultants as rhetorical wizards who engineer waves of management fashion, firms and consultants are treated as boundedly rational actors who chase the secrets of success by mimicking their highest-performing peers. Computational experiments demonstrate that consultant-driven versions of this dynamic in which the outcomes of firms are strongly conditioned by their choice of consultant are robustly faddish. The invasion of boom markets by low-quality consultants undercuts popular innovations while simultaneously restarting the fashion cycle by prompting the flight of high-quality consultants into less densely occupied niches. Computational experiments also indicate conditions involving consultant mobility, aspiration levels, mimic probabilities, and client-provider matching that attenuate faddishness.

Focus: Bounded Rationality and the History of Science. Introduction.

PubMed

Cowles, Henry M; Deringer, William; Dick, Stephanie; Webster, Colin

2015-09-01

Historians of science see knowledge and its claimants as constrained by myriad factors. These limitations range from the assumptions and commitments of scientific practitioners to the material and ideational contexts of their practice. The precise nature of such limits and the relations among them remains an open question in the history of science. The essays in this Focus section address this question by examining one influential portrayal of constraints--Herbert Simon's theory of "bounded rationality"--as well as the responses to which it has given rise over the last half century.

Comparable Stocks, Boundedly Rational Stock Markets and IPO Entry Rates

PubMed Central

Chok, Jay; Qian, Jifeng

2013-01-01

In this study, we examine how initial public offerings (IPO) entry rates are affected when stock markets are boundedly rational and IPO firms infer information from their counterparts in the market. We hypothesize a curvilinear relationship between the number of comparable stocks and initial public offerings (IPO) entry rates into the NASDAQ Stock Exchange. Furthermore, we argue that trading volume and changes in stock returns partially mediates the relationship between the number of comparable stocks and IPO entry rates. The statistical evidence provides strong support for the hypotheses. PMID:23690924

Comparable stocks, boundedly rational stock markets and IPO entry rates.

PubMed

Chok, Jay; Qian, Jifeng

2013-01-01

In this study, we examine how initial public offerings (IPO) entry rates are affected when stock markets are boundedly rational and IPO firms infer information from their counterparts in the market. We hypothesize a curvilinear relationship between the number of comparable stocks and initial public offerings (IPO) entry rates into the NASDAQ Stock Exchange. Furthermore, we argue that trading volume and changes in stock returns partially mediates the relationship between the number of comparable stocks and IPO entry rates. The statistical evidence provides strong support for the hypotheses.

Thermal Destruction Of CB Contaminants Bound On Building ...

EPA Pesticide Factsheets

Symposium Paper An experimental and theoretical program has been initiated by the U.S. EPA to investigate issues of chemical/biological agent destruction in incineration systems when the agent in question is bound on common porous building interior materials. This program includes 3-dimensional computational fluid dynamics modeling with matrix-bound agent destruction kinetics, bench-scale experiments to determine agent destruction kinetics while bound on various matrices, and pilot-scale experiments to scale-up the bench-scale experiments to a more practical scale. Finally, model predictions are made to predict agent destruction and combustion conditions in two full-scale incineration systems that are typical of modern combustor design.

Agent-based modeling of deforestation in southern Yucatán, Mexico, and reforestation in the Midwest United States

PubMed Central

Manson, Steven M.; Evans, Tom

2007-01-01

We combine mixed-methods research with integrated agent-based modeling to understand land change and economic decision making in the United States and Mexico. This work demonstrates how sustainability science benefits from combining integrated agent-based modeling (which blends methods from the social, ecological, and information sciences) and mixed-methods research (which interleaves multiple approaches ranging from qualitative field research to quantitative laboratory experiments and interpretation of remotely sensed imagery). We test assumptions of utility-maximizing behavior in household-level landscape management in south-central Indiana, linking parcel data, land cover derived from aerial photography, and findings from laboratory experiments. We examine the role of uncertainty and limited information, preferences, differential demographic attributes, and past experience and future time horizons. We also use evolutionary programming to represent bounded rationality in agriculturalist households in the southern Yucatán of Mexico. This approach captures realistic rule of thumb strategies while identifying social and environmental factors in a manner similar to econometric models. These case studies highlight the role of computational models of decision making in land-change contexts and advance our understanding of decision making in general. PMID:18093928

Moral satisficing: rethinking moral behavior as bounded rationality.

PubMed

Gigerenzer, Gerd

2010-07-01

What is the nature of moral behavior? According to the study of bounded rationality, it results not from character traits or rational deliberation alone, but from the interplay between mind and environment. In this view, moral behavior is based on pragmatic social heuristics rather than moral rules or maximization principles. These social heuristics are not good or bad per se, but solely in relation to the environments in which they are used. This has methodological implications for the study of morality: Behavior needs to be studied in social groups as well as in isolation, in natural environments as well as in labs. It also has implications for moral policy: Only by accepting the fact that behavior is a function of both mind and environmental structures can realistic prescriptive means of achieving moral goals be developed. Copyright © 2010 Cognitive Science Society, Inc.

The Control of Multi-Agent Systems (MAS)

DTIC Science & Technology

2004-09-01

Mixes rational (ground state E0 = |↓>) & emotional (excited state E1 = |↑>) • M(I, S) -> shifts agent |↑> or |↓> w/P(1) (Gibson, 1986; Caccioppo...1951): a group is more than sum of parts – Luce & Raiffa (1967): individual rational perspective cannot account for the “social” (viz., game and...deception • Assumption: Reality is bistable with I that is mostly inaccessible 2 9th ICCRTS, Copenhagen, 9/2004 Paradoxes • Rational , Individual: ∑xi

A theoretical perspective on road safety communication campaigns.

PubMed

Elvik, Rune

2016-12-01

This paper proposes a theoretical perspective on road safety communication campaigns, which may help in identifying the conditions under which such campaigns can be effective. The paper proposes that, from a theoretical point of view, it is reasonable to assume that road user behaviour is, by and large, subjectively rational. This means that road users are assumed to behave the way they think is best. If this assumption is accepted, the best theoretical prediction is that road safety campaigns consisting of persuasive messages only will have no effect on road user behaviour and accordingly no effect on accidents. This theoretical prediction is not supported by meta-analyses of studies that have evaluated the effects of road safety communication campaigns. These analyses conclude that, on the average, such campaigns are associated with an accident reduction. The paper discusses whether this finding can be explained theoretically. The discussion relies on the distinction made by many modern theorists between bounded and perfect rationality. Road user behaviour is characterised by bounded rationality. Hence, if road users can gain insight into the bounds of their rationality, so that they see advantages to themselves of changing behaviour, they are likely to do so. It is, however, largely unknown whether such a mechanism explains why some road safety communication campaigns have been found to be more effective than others. Copyright © 2015 Elsevier Ltd. All rights reserved.

James Moffett's Mistake: Ignoring the Rational Capacities of the Other

ERIC Educational Resources Information Center

Donehower, Kim

2013-01-01

Using Alasdair MacIntyre's theory of tradition-bound rationalities, this essay analyses James Moffett's depiction of the censors who opposed his "Interactions" textbook series in the Kanawha County, West Virginia, schools. Many reviewers have found Moffett's analysis of the censors in "Storm in the Mountains" even-handed and…

Generalized Skyrme model with the loosely bound potential

NASA Astrophysics Data System (ADS)

Gudnason, Sven Bjarke; Zhang, Baiyang; Ma, Nana

2016-12-01

We study a generalization of the loosely bound Skyrme model which consists of the Skyrme model with a sixth-order derivative term—motivated by its fluidlike properties—and the second-order loosely bound potential—motivated by lowering the classical binding energies of higher-charged Skyrmions. We use the rational map approximation for the Skyrmion of topological charge B =4 , calculate the binding energy of the latter, and estimate the systematic error in using this approximation. In the parameter space that we can explore within the rational map approximation, we find classical binding energies as low as 1.8%, and once taking into account the contribution from spin-isospin quantization, we obtain binding energies as low as 5.3%. We also calculate the contribution from the sixth-order derivative term to the electric charge density and axial coupling.

The origin of bounded rationality and intelligence.

PubMed

Lo, Andrew W

2013-09-01

Rational economic behavior in which individuals maximize their own self-interest is only one of many possible types of behavior that arise from natural selection. Given an initial population of individuals, each assigned a purely arbitrary behavior with respect to a binary choice problem, and assuming that offspring behave identically to their parents, only those behaviors linked to reproductive success will survive, and less successful behaviors will disappear exponentially fast. This framework yields a single evolutionary explanation for the origin of several behaviors that have been observed in organisms ranging from bacteria to humans, including risk-sensitive foraging, risk aversion, loss aversion, probability matching, randomization, and diversification. The key to understanding which types of behavior are more likely to survive is how behavior affects reproductive success in a given population's environment. From this perspective, intelligence is naturally defined as behavior that increases the likelihood of reproductive success, and bounds on rationality are determined by physiological and environmental constraints.

Rational expectations, psychology and inductive learning via moving thresholds

NASA Astrophysics Data System (ADS)

Lamba, H.; Seaman, T.

2008-06-01

This paper modifies a previously introduced class of heterogeneous agent models in a way that allows for the inclusion of different types of agent motivations and behaviours in a consistent manner. The agents operate within a highly simplified environment where they are only able to be long or short one unit of the asset. The price of the asset is influenced by both an external information stream and the demand of the agents. The current strategy of each agent is defined by a pair of moving thresholds straddling the current price. When the price crosses either of the thresholds for a particular agent, that agent switches position and a new pair of thresholds is generated. The threshold dynamics can mimic different sources of investor motivation, running the gamut from purely rational information-processing, through rational (but often undesirable) behaviour induced by perverse incentives and moral hazards, to purely psychological effects. The simplest model of this kind precisely conforms to the Efficient Market Hypothesis (EMH) and this allows causal relationships to be established between actions at the agent level and violations of EMH price statistics at the global level. In particular, the effects of herding behaviour and perverse incentives are examined.

Broadening the Debate: Comments on Michael J. Feuer's "Moderating the Debate"

ERIC Educational Resources Information Center

Robertson, Emily

2009-01-01

In "Moderating the Debate: Rationality and the Promise of American Education", Michael Feuer argues that insights from cognitive science and the theory of bounded rationality can help us understand why educational policy makers overreach in seeking optimal solutions to educational problems. In this essay, Emily Robertson argues that cognitive…

Dynamic pricing of network goods with boundedly rational consumers.

PubMed

Radner, Roy; Radunskaya, Ami; Sundararajan, Arun

2014-01-07

We present a model of dynamic monopoly pricing for a good that displays network effects. In contrast with the standard notion of a rational-expectations equilibrium, we model consumers as boundedly rational and unable either to pay immediate attention to each price change or to make accurate forecasts of the adoption of the network good. Our analysis shows that the seller's optimal price trajectory has the following structure: The price is low when the user base is below a target level, is high when the user base is above the target, and is set to keep the user base stationary once the target level has been attained. We show that this pricing policy is robust to a number of extensions, which include the product's user base evolving over time and consumers basing their choices on a mixture of a myopic and a "stubborn" expectation of adoption. Our results differ significantly from those that would be predicted by a model based on rational-expectations equilibrium and are more consistent with the pricing of network goods observed in practice.

Dynamic pricing of network goods with boundedly rational consumers

PubMed Central

Radner, Roy; Radunskaya, Ami; Sundararajan, Arun

2014-01-01

We present a model of dynamic monopoly pricing for a good that displays network effects. In contrast with the standard notion of a rational-expectations equilibrium, we model consumers as boundedly rational and unable either to pay immediate attention to each price change or to make accurate forecasts of the adoption of the network good. Our analysis shows that the seller’s optimal price trajectory has the following structure: The price is low when the user base is below a target level, is high when the user base is above the target, and is set to keep the user base stationary once the target level has been attained. We show that this pricing policy is robust to a number of extensions, which include the product’s user base evolving over time and consumers basing their choices on a mixture of a myopic and a “stubborn” expectation of adoption. Our results differ significantly from those that would be predicted by a model based on rational-expectations equilibrium and are more consistent with the pricing of network goods observed in practice. PMID:24367101

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.

Elucidating the druggable interface of protein-protein interactions using fragment docking and coevolutionary analysis.

PubMed

Bai, Fang; Morcos, Faruck; Cheng, Ryan R; Jiang, Hualiang; Onuchic, José N

2016-12-13

Protein-protein interactions play a central role in cellular function. Improving the understanding of complex formation has many practical applications, including the rational design of new therapeutic agents and the mechanisms governing signal transduction networks. The generally large, flat, and relatively featureless binding sites of protein complexes pose many challenges for drug design. Fragment docking and direct coupling analysis are used in an integrated computational method to estimate druggable protein-protein interfaces. (i) This method explores the binding of fragment-sized molecular probes on the protein surface using a molecular docking-based screen. (ii) The energetically favorable binding sites of the probes, called hot spots, are spatially clustered to map out candidate binding sites on the protein surface. (iii) A coevolution-based interface interaction score is used to discriminate between different candidate binding sites, yielding potential interfacial targets for therapeutic drug design. This approach is validated for important, well-studied disease-related proteins with known pharmaceutical targets, and also identifies targets that have yet to be studied. Moreover, therapeutic agents are proposed by chemically connecting the fragments that are strongly bound to the hot spots.

Economic reasoning and artificial intelligence.

PubMed

Parkes, David C; Wellman, Michael P

2015-07-17

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

Bioconjugation of luminescent silicon quantum dots to gadolinium ions for bioimaging applications

NASA Astrophysics Data System (ADS)

Erogbogbo, Folarin; Chang, Ching-Wen; May, Jasmine L.; Liu, Liwei; Kumar, Rajiv; Law, Wing-Cheung; Ding, Hong; Yong, Ken Tye; Roy, Indrajit; Sheshadri, Mukund; Swihart, Mark T.; Prasad, Paras N.

2012-08-01

Luminescent imaging agents and MRI contrast agents are desirable components in the rational design of multifunctional nanoconstructs for biological imaging applications. Luminescent biocompatible silicon quantum dots (SiQDs) and gadolinium chelates can be applied for fluorescence microscopy and MRI, respectively. Here, we report the first synthesis of a nanocomplex incorporating SiQDs and gadolinium ions (Gd3+) for biological applications. The nanoconstruct is composed of a PEGylated micelle, with hydrophobic SiQDs in its core, covalently bound to DOTA-chelated Gd3+. Dynamic light scattering reveals a radius of 85 nm for these nanoconstructs, which is consistent with the electron microscopy results depicting radii ranging from 25 to 60 nm. Cellular uptake of the probes verified that they maintain their optical properties within the intracellular environment. The magnetic resonance relaxivity of the nanoconstruct was 2.4 mM-1 s-1 (in terms of Gd3+ concentration), calculated to be around 6000 mM-1 s-1 per nanoconstruct. These desirable optical and relaxivity properties of the newly developed probe open the door for use of SiQDs in future multimodal applications such as tumour imaging.Luminescent imaging agents and MRI contrast agents are desirable components in the rational design of multifunctional nanoconstructs for biological imaging applications. Luminescent biocompatible silicon quantum dots (SiQDs) and gadolinium chelates can be applied for fluorescence microscopy and MRI, respectively. Here, we report the first synthesis of a nanocomplex incorporating SiQDs and gadolinium ions (Gd3+) for biological applications. The nanoconstruct is composed of a PEGylated micelle, with hydrophobic SiQDs in its core, covalently bound to DOTA-chelated Gd3+. Dynamic light scattering reveals a radius of 85 nm for these nanoconstructs, which is consistent with the electron microscopy results depicting radii ranging from 25 to 60 nm. Cellular uptake of the probes verified that they maintain their optical properties within the intracellular environment. The magnetic resonance relaxivity of the nanoconstruct was 2.4 mM-1 s-1 (in terms of Gd3+ concentration), calculated to be around 6000 mM-1 s-1 per nanoconstruct. These desirable optical and relaxivity properties of the newly developed probe open the door for use of SiQDs in future multimodal applications such as tumour imaging. Electronic supplementary information (ESI) available: SEM images of MSiQD-Gd3+, DLS plot of MSiQD-NH2, images of Gd3+-functionalized Si QDs micelles in water, plot of percentages of Gd3+ leaked from original sample, and determination of free Gd3+ in solutions of Gd chelates. See DOI: 10.1039/c2nr31002c

A Comparative Study of Probability Collectives Based Multi-agent Systems and Genetic Algorithms

NASA Technical Reports Server (NTRS)

Huang, Chien-Feng; Wolpert, David H.; Bieniawski, Stefan; Strauss, Charles E. M.

2005-01-01

We compare Genetic Algorithms (GA's) with Probability Collectives (PC), a new framework for distributed optimization and control. In contrast to GA's, PC-based methods do not update populations of solutions. Instead they update an explicitly parameterized probability distribution p over the space of solutions. That updating of p arises as the optimization of a functional of p. The functional is chosen so that any p that optimizes it should be p peaked about good solutions. The PC approach works in both continuous and discrete problems. It does not suffer from the resolution limitation of the finite bit length encoding of parameters into GA alleles. It also has deep connections with both game theory and statistical physics. We review the PC approach using its motivation as the information theoretic formulation of bounded rationality for multi-agent systems. It is then compared with GA's on a diverse set of problems. To handle high dimensional surfaces, in the PC method investigated here p is restricted to a product distribution. Each distribution in that product is controlled by a separate agent. The test functions were selected for their difficulty using either traditional gradient descent or genetic algorithms. On those functions the PC-based approach significantly outperforms traditional GA's in both rate of descent, trapping in false minima, and long term optimization.

Monopoly models with time-varying demand function

NASA Astrophysics Data System (ADS)

Cavalli, Fausto; Naimzada, Ahmad

2018-05-01

We study a family of monopoly models for markets characterized by time-varying demand functions, in which a boundedly rational agent chooses output levels on the basis of a gradient adjustment mechanism. After presenting the model for a generic framework, we analytically study the case of cyclically alternating demand functions. We show that both the perturbation size and the agent's reactivity to profitability variation signals can have counterintuitive roles on the resulting period-2 cycles and on their stability. In particular, increasing the perturbation size can have both a destabilizing and a stabilizing effect on the resulting dynamics. Moreover, in contrast with the case of time-constant demand functions, the agent's reactivity is not just destabilizing, but can improve stability, too. This means that a less cautious behavior can provide better performance, both with respect to stability and to achieved profits. We show that, even if the decision mechanism is very simple and is not able to always provide the optimal production decisions, achieved profits are very close to those optimal. Finally, we show that in agreement with the existing empirical literature, the price series obtained simulating the proposed model exhibit a significant deviation from normality and large volatility, in particular when underlying deterministic dynamics become unstable and complex.

Rational and Boundedly Rational Behavior in a Binary Choice Sender-Receiver Game

ERIC Educational Resources Information Center

Landi, Massimiliano; Colucci, Domenico

2008-01-01

The authors investigate the strategic rationale behind the message sent by Osama bin Laden on the eve of the 2004 U.S. Presidential elections. They model this situation as a signaling game in which a population of receivers takes a binary choice, the outcome is decided by majority rule, sender and receivers have conflicting interests, and there is…

When does "economic man" dominate social behavior?

PubMed

Camerer, Colin F; Fehr, Ernst

2006-01-06

The canonical model in economics considers people to be rational and self-regarding. However, much evidence challenges this view, raising the question of when "Economic Man" dominates the outcome of social interactions, and when bounded rationality or other-regarding preferences dominate. Here we show that strategic incentives are the key to answering this question. A minority of self-regarding individuals can trigger a "noncooperative" aggregate outcome if their behavior generates incentives for the majority of other-regarding individuals to mimic the minority's behavior. Likewise, a minority of other-regarding individuals can generate a "cooperative" aggregate outcome if their behavior generates incentives for a majority of self-regarding people to behave cooperatively. Similarly, in strategic games, aggregate outcomes can be either far from or close to Nash equilibrium if players with high degrees of strategic thinking mimic or erase the effects of others who do very little strategic thinking. Recently developed theories of other-regarding preferences and bounded rationality explain these findings and provide better predictions of actual aggregate behavior than does traditional economic theory.

Can Computers be Social?

NASA Astrophysics Data System (ADS)

Ekdahl, Bertil

2002-09-01

Of main concern in agent based computing is the conception that software agents can attain socially responsible behavior. This idea has its origin in the need for agents to interact with one another in a cooperating manner. Such interplay between several agents can be seen as a combinatorial play where the rules are fixed and the actors are supposed to closely analyze the play in order to behave rational. This kind of rationality has successfully being mathematically described. When the social behavior is extended beyond rational behavior, mere mathematical analysis falls short. For such behavior language is decisive for transferring concepts and language is a holistic entity that cannot be analyzed and defined mathematically. Accordingly, computers cannot be furnished with a language in the sense that meaning can be conveyed and consequently they lack all the necessary properties to be made social. The attempts to postulate mental properties to computer programs are a misconception that is blamed the lack of true understanding of language and especially the relation between formal system and its semantics.

Action understanding as inverse planning.

PubMed

Baker, Chris L; Saxe, Rebecca; Tenenbaum, Joshua B

2009-12-01

Humans are adept at inferring the mental states underlying other agents' actions, such as goals, beliefs, desires, emotions and other thoughts. We propose a computational framework based on Bayesian inverse planning for modeling human action understanding. The framework represents an intuitive theory of intentional agents' behavior based on the principle of rationality: the expectation that agents will plan approximately rationally to achieve their goals, given their beliefs about the world. The mental states that caused an agent's behavior are inferred by inverting this model of rational planning using Bayesian inference, integrating the likelihood of the observed actions with the prior over mental states. This approach formalizes in precise probabilistic terms the essence of previous qualitative approaches to action understanding based on an "intentional stance" [Dennett, D. C. (1987). The intentional stance. Cambridge, MA: MIT Press] or a "teleological stance" [Gergely, G., Nádasdy, Z., Csibra, G., & Biró, S. (1995). Taking the intentional stance at 12 months of age. Cognition, 56, 165-193]. In three psychophysical experiments using animated stimuli of agents moving in simple mazes, we assess how well different inverse planning models based on different goal priors can predict human goal inferences. The results provide quantitative evidence for an approximately rational inference mechanism in human goal inference within our simplified stimulus paradigm, and for the flexible nature of goal representations that human observers can adopt. We discuss the implications of our experimental results for human action understanding in real-world contexts, and suggest how our framework might be extended to capture other kinds of mental state inferences, such as inferences about beliefs, or inferring whether an entity is an intentional agent.

Kant on euthanasia and the duty to die: clearing the air.

PubMed

Cholbi, Michael

2015-08-01

Thanks to recent scholarship, Kant is no longer seen as the dogmatic opponent of suicide that he appears to be at first glance. However, some interpreters have recently argued for a Kantian view of the morality of suicide with surprising, even radical, implications. More specifically, they have argued that Kantianism (1) requires that those with dementia or other rationality-eroding conditions end their lives before their condition results in their loss of identity as moral agents and (2) requires subjecting the fully demented or those confronting future dementia to non-voluntary euthanasia. Properly understood, Kant's ethics have neither of these implications (1) wrongly assumes that rational agents' duty of self-preservation entails a duty of self-destruction when they become non-rational, (2) further neglects Kant's distinction between duties to self and duties to others and wrongly assumes that duties can be owed to rational agents only during the time of their existence. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

An evolutionary model of cooperation, fairness and altruistic punishment in public good games.

PubMed

Hetzer, Moritz; Sornette, Didier

2013-01-01

We identify and explain the mechanisms that account for the emergence of fairness preferences and altruistic punishment in voluntary contribution mechanisms by combining an evolutionary perspective together with an expected utility model. We aim at filling a gap between the literature on the theory of evolution applied to cooperation and punishment, and the empirical findings from experimental economics. The approach is motivated by previous findings on other-regarding behavior, the co-evolution of culture, genes and social norms, as well as bounded rationality. Our first result reveals the emergence of two distinct evolutionary regimes that force agents to converge either to a defection state or to a state of coordination, depending on the predominant set of self- or other-regarding preferences. Our second result indicates that subjects in laboratory experiments of public goods games with punishment coordinate and punish defectors as a result of an aversion against disadvantageous inequitable outcomes. Our third finding identifies disadvantageous inequity aversion as evolutionary dominant and stable in a heterogeneous population of agents endowed initially only with purely self-regarding preferences. We validate our model using previously obtained results from three independently conducted experiments of public goods games with punishment.

An Evolutionary Model of Cooperation, Fairness and Altruistic Punishment in Public Good Games

PubMed Central

Hetzer, Moritz; Sornette, Didier

2013-01-01

We identify and explain the mechanisms that account for the emergence of fairness preferences and altruistic punishment in voluntary contribution mechanisms by combining an evolutionary perspective together with an expected utility model. We aim at filling a gap between the literature on the theory of evolution applied to cooperation and punishment, and the empirical findings from experimental economics. The approach is motivated by previous findings on other-regarding behavior, the co-evolution of culture, genes and social norms, as well as bounded rationality. Our first result reveals the emergence of two distinct evolutionary regimes that force agents to converge either to a defection state or to a state of coordination, depending on the predominant set of self- or other-regarding preferences. Our second result indicates that subjects in laboratory experiments of public goods games with punishment coordinate and punish defectors as a result of an aversion against disadvantageous inequitable outcomes. Our third finding identifies disadvantageous inequity aversion as evolutionary dominant and stable in a heterogeneous population of agents endowed initially only with purely self-regarding preferences. We validate our model using previously obtained results from three independently conducted experiments of public goods games with punishment. PMID:24260101

Complex Nonlinear Dynamic System of Oligopolies Price Game with Heterogeneous Players Under Noise

NASA Astrophysics Data System (ADS)

Liu, Feng; Li, Yaguang

A nonlinear four oligopolies price game with heterogeneous players, that are boundedly rational and adaptive, is built using two different special demand costs. Based on the theory of complex discrete dynamical system, the stability and the existing equilibrium point are investigated. The complex dynamic behavior is presented via bifurcation diagrams, the Lyapunov exponents to show equilibrium state, bifurcation and chaos with the variation in parameters. As disturbance is ubiquitous in economic systems, this paper focuses on the analysis of delay feedback control method under noise circumstances. Stable dynamics is confirmed to depend mainly on the low price adjustment speed, and if all four players have limited opportunities to stabilize the market, the new adaptive player facing profits of scale are found to be higher than the incumbents of bounded rational.

Rational Inference of Beliefs and Desires From Emotional Expressions.

PubMed

Wu, Yang; Baker, Chris L; Tenenbaum, Joshua B; Schulz, Laura E

2018-04-01

We investigated people's ability to infer others' mental states from their emotional reactions, manipulating whether agents wanted, expected, and caused an outcome. Participants recovered agents' desires throughout. When the agent observed, but did not cause the outcome, participants' ability to recover the agent's beliefs depended on the evidence they got (i.e., her reaction only to the actual outcome or to both the expected and actual outcomes; Experiments 1 and 2). When the agent caused the event, participants' judgments also depended on the probability of the action (Experiments 3 and 4); when actions were improbable given the mental states, people failed to recover the agent's beliefs even when they saw her react to both the anticipated and actual outcomes. A Bayesian model captured human performance throughout (rs ≥ .95), consistent with the proposal that people rationally integrate information about others' actions and emotional reactions to infer their unobservable mental states. Copyright © 2017 Cognitive Science Society, Inc.

Evolutionary game analysis and regulatory strategies for online group-buying based on system dynamics

NASA Astrophysics Data System (ADS)

Jiang, Zhong-Zhong; He, Na; Qin, Xuwei; Ip, W. H.; Wu, C. H.; Yung, K. L.

2018-07-01

The emergence of online group-buying provides a new consumption pattern for consumers in e-commerce era. However, many consumers realize that their own interests sometimes can't be guaranteed in the group-buying market due to the lack of being regulated. This paper aims to develop effective regulation strategies for online group-buying market. To the best of our knowledge, most existing studies assume that three parties in online group-buying market, i.e. the retailer, the group-buying platform and the consumer, are perfectly rational. To better understand the decision process, in this paper, we incorporate the concept of bounded rationality into consideration. Firstly, a three-parties evolutionary game model is established to study each player's game strategy based on bounded rationality. Secondly, the game model is simulated as a whole by adopting system dynamics to analyze its stability. Finally, theoretical analysis and extensive computational experiments are conducted to obtain the managerial insights and regulation strategies for online group-buying market. Our results clearly demonstrate that a suitable bonus-penalty measure can promote the healthy development of online group-buying market.

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.

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.

An evolutionary model of bounded rationality and intelligence.

PubMed

Brennan, Thomas J; Lo, Andrew W

2012-01-01

Most economic theories are based on the premise that individuals maximize their own self-interest and correctly incorporate the structure of their environment into all decisions, thanks to human intelligence. The influence of this paradigm goes far beyond academia-it underlies current macroeconomic and monetary policies, and is also an integral part of existing financial regulations. However, there is mounting empirical and experimental evidence, including the recent financial crisis, suggesting that humans do not always behave rationally, but often make seemingly random and suboptimal decisions. Here we propose to reconcile these contradictory perspectives by developing a simple binary-choice model that takes evolutionary consequences of decisions into account as well as the role of intelligence, which we define as any ability of an individual to increase its genetic success. If no intelligence is present, our model produces results consistent with prior literature and shows that risks that are independent across individuals in a generation generally lead to risk-neutral behaviors, but that risks that are correlated across a generation can lead to behaviors such as risk aversion, loss aversion, probability matching, and randomization. When intelligence is present the nature of risk also matters, and we show that even when risks are independent, either risk-neutral behavior or probability matching will occur depending upon the cost of intelligence in terms of reproductive success. In the case of correlated risks, we derive an implicit formula that shows how intelligence can emerge via selection, why it may be bounded, and how such bounds typically imply the coexistence of multiple levels and types of intelligence as a reflection of varying environmental conditions. Rational economic behavior in which individuals maximize their own self interest is only one of many possible types of behavior that arise from natural selection. The key to understanding which types of behavior are more likely to survive is how behavior affects reproductive success in a given population's environment. From this perspective, intelligence is naturally defined as behavior that increases the probability of reproductive success, and bounds on rationality are determined by physiological and environmental constraints.

An Evolutionary Model of Bounded Rationality and Intelligence

PubMed Central

Brennan, Thomas J.; Lo, Andrew W.

2012-01-01

Background Most economic theories are based on the premise that individuals maximize their own self-interest and correctly incorporate the structure of their environment into all decisions, thanks to human intelligence. The influence of this paradigm goes far beyond academia–it underlies current macroeconomic and monetary policies, and is also an integral part of existing financial regulations. However, there is mounting empirical and experimental evidence, including the recent financial crisis, suggesting that humans do not always behave rationally, but often make seemingly random and suboptimal decisions. Methods and Findings Here we propose to reconcile these contradictory perspectives by developing a simple binary-choice model that takes evolutionary consequences of decisions into account as well as the role of intelligence, which we define as any ability of an individual to increase its genetic success. If no intelligence is present, our model produces results consistent with prior literature and shows that risks that are independent across individuals in a generation generally lead to risk-neutral behaviors, but that risks that are correlated across a generation can lead to behaviors such as risk aversion, loss aversion, probability matching, and randomization. When intelligence is present the nature of risk also matters, and we show that even when risks are independent, either risk-neutral behavior or probability matching will occur depending upon the cost of intelligence in terms of reproductive success. In the case of correlated risks, we derive an implicit formula that shows how intelligence can emerge via selection, why it may be bounded, and how such bounds typically imply the coexistence of multiple levels and types of intelligence as a reflection of varying environmental conditions. Conclusions Rational economic behavior in which individuals maximize their own self interest is only one of many possible types of behavior that arise from natural selection. The key to understanding which types of behavior are more likely to survive is how behavior affects reproductive success in a given population’s environment. From this perspective, intelligence is naturally defined as behavior that increases the probability of reproductive success, and bounds on rationality are determined by physiological and environmental constraints. PMID:23185602

Fluoride mechanisms.

PubMed

ten Cate, J M; van Loveren, C

1999-10-01

This article discusses fluoride mechanisms in relation to dental caries. The authors specifically address firmly bound versus loosely bound fluoride; different fluoride active ingredients; fluoride and demineralization and remineralization; fluoride slow-release devices and F-releasing dental materials; antimicrobial effects of fluoride; the uptake of fluoride by oral bacteria; inhibition of enolase, protein-intruding ATPase and sugar transport; the various aspects of plaque as it relates to fluoride; and the rational use of fluoride.

Administrative gatekeeping - a third way between unrestricted patient advocacy and bedside rationing.

PubMed

Lauridsen, Sigurd

2009-06-01

The inevitable need for rationing of healthcare has apparently presented the medical profession with the dilemma of choosing the lesser of two evils. Physicians appear to be obliged to adopt either an implausible version of traditional professional ethics or an equally problematic ethics of bedside rationing. The former requires unrestricted advocacy of patients but prompts distrust, moral hazard and unfairness. The latter commits physicians to rationing at the bedside; but it is bound to introduce unfair inequalities among patients and lack of political accountability towards citizens. In this paper I shall argue that this dilemma is false, since a third intermediate alternative exists. This alternative, which I term 'administrative gatekeeping', makes it possible for physicians to be involved in rationing while at the same time being genuine advocates of their patients. According to this ideal, physicians are required to follow fair rules of rationing adopted at higher organizational levels within healthcare systems. At the same time, however, they are prohibited from including considerations of cost in their clinical decisions.

Re-visions of rationality?

PubMed

Newell, Ben R

2005-01-01

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

Prospect balancing theory: Bounded rationality of drivers' speed choice.

PubMed

Schmidt-Daffy, Martin

2014-02-01

This paper introduces a new approach to model the psychological determinants of drivers' speed choice: prospect-balancing theory. The theory transfers psychological insight into the bounded rationality of human decision-making to the field of driving behaviour. Speed choice is conceptualized as a trade-off between two options for action: the option to drive slower and the option to drive faster. Each option is weighted according to a subjective value and a subjectively weighted probability attributed to the achievement of the associated action goal; e.g. to avoid an accident by driving more slowly. The theory proposes that the subjective values and weightings of probability differ systematically from the objective conditions and thereby usually favour a cautious speed choice. A driving simulation study with 24 male participants supports this assumption. In a conflict between a monetary gain in case of fast arrival and a monetary loss in case of a collision with a deer, participants chose a velocity lower than that which would maximize their pay-out. Participants' subjective certainty of arriving in time and of avoiding a deer collision assessed at different driving speeds diverged from the respective objective probabilities in accordance with the observed bias in choice of speed. Results suggest that the bounded rationality of drivers' speed choice might be used to support attempts to improve road safety. Thus, understanding the motivational and perceptual determinants of this intuitive mode of decision-making might be a worthwhile focus of future research. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Role of Dysfunctional Myths in a Decision-Making Process under Bounded Rationality: A Complex Dynamical Systems Perspective.

PubMed

Stamovlasis, Dimitrios; Vaiopoulou, Julie

2017-07-01

The present study examines the factors influencing a decision-making process, with specific focus on the role of dysfunctional myths (DM). DM are thoughts or beliefs that are rather irrational, however influential to people's decisions. In this paper a decision-making process regarding the career choice of university students majoring in natural sciences and education (N=496) is examined by analyzing survey data taken via Career Decision Making Difficulties Questionnaire (CDDQ). The difficulty of making the choice and the certainty about one's decision were the state variables, while the independent variables were factors related to the lack of information or knowledge needed, which actually reflect a bounded rationality. Cusp catastrophe analysis, based on both least squares and maximum likelihood procedures, showed that the nonlinear models predicting the two state variables were superior to linear alternatives. Factors related to lack of knowledge about the steps involved in the process of career decision-making, lack of information about the various occupations, lack of information about self and lack of motivation acted as asymmetry, while dysfunctional myths acted as bifurcation factor for both state variables. The catastrophe model, grounded in empirical data, revealed a unique role for DM and a better interpretation within the context of complexity and the notion of bounded rationality. The analysis opens the nonlinear dynamical systems (NDS) perspective in studying decision-making processes. Theoretical and practical implications are discussed.

Construction of a Learning Agent Handling Its Rewards According to Environmental Situations

NASA Astrophysics Data System (ADS)

Moriyama, Koichi; Numao, Masayuki

The authors aim at constructing an agent which learns appropriate actions in a Multi-Agent environment with and without social dilemmas. For this aim, the agent must have nonrationality that makes it give up its own profit when it should do that. Since there are many studies on rational learning that brings more and more profit, it is desirable to utilize them for constructing the agent. Therefore, we use a reward-handling manner that makes internal evaluation from the agent's rewards, and then the agent learns actions by a rational learning method with the internal evaluation. If the agent has only a fixed manner, however, it does not act well in the environment with and without dilemmas. Thus, the authors equip the agent with several reward-handling manners and criteria for selecting an effective one for the environmental situation. In the case of humans, what generates the internal evaluation is usually called emotion. Hence, this study also aims at throwing light on emotional activities of humans from a constructive view. In this paper, we divide a Multi-Agent environment into three situations and construct an agent having the reward-handling manners and the criteria. We observe that the agent acts well in all the three Multi-Agent situations composed of homogeneous agents.

Governator vs. Hunter and Aggregator: A simulation of party competition with vote-seeking and office-seeking rules.

PubMed

Lehrer, Roni; Schumacher, Gijs

2018-01-01

The policy positions parties choose are central to both attracting voters and forming coalition governments. How then should parties choose positions to best represent voters? Laver and Sergenti show that in an agent-based model with boundedly rational actors a decision rule (Aggregator) that takes the mean policy position of its supporters is the best rule to achieve high congruence between voter preferences and party positions. But this result only pertains to representation by the legislature, not representation by the government. To evaluate this we add a coalition formation procedure with boundedly rational parties to the Laver and Sergenti model of party competition. We also add two new decision rules that are sensitive to government formation outcomes rather than voter positions. We develop two simulations: a single-rule one in which parties with the same rule compete and an evolutionary simulation in which parties with different rules compete. In these simulations we analyze party behavior under a large number of different parameters that describe real-world variance in political parties' motives and party system characteristics. Our most important conclusion is that Aggregators also produce the best match between government policy and voter preferences. Moreover, even though citizens often frown upon politicians' interest in the prestige and rents that come with winning political office (office pay-offs), we find that citizens actually receive better representation by the government if politicians are motivated by these office pay-offs in contrast to politicians with ideological motivations (policy pay-offs). Finally, we show that while more parties are linked to better political representation, how parties choose policy positions affects political representation as well. Overall, we conclude that to understand variation in the quality of political representation scholars should look beyond electoral systems and take into account variation in party behavior as well.

Governator vs. Hunter and Aggregator: A simulation of party competition with vote-seeking and office-seeking rules

PubMed Central

2018-01-01

The policy positions parties choose are central to both attracting voters and forming coalition governments. How then should parties choose positions to best represent voters? Laver and Sergenti show that in an agent-based model with boundedly rational actors a decision rule (Aggregator) that takes the mean policy position of its supporters is the best rule to achieve high congruence between voter preferences and party positions. But this result only pertains to representation by the legislature, not representation by the government. To evaluate this we add a coalition formation procedure with boundedly rational parties to the Laver and Sergenti model of party competition. We also add two new decision rules that are sensitive to government formation outcomes rather than voter positions. We develop two simulations: a single-rule one in which parties with the same rule compete and an evolutionary simulation in which parties with different rules compete. In these simulations we analyze party behavior under a large number of different parameters that describe real-world variance in political parties’ motives and party system characteristics. Our most important conclusion is that Aggregators also produce the best match between government policy and voter preferences. Moreover, even though citizens often frown upon politicians’ interest in the prestige and rents that come with winning political office (office pay-offs), we find that citizens actually receive better representation by the government if politicians are motivated by these office pay-offs in contrast to politicians with ideological motivations (policy pay-offs). Finally, we show that while more parties are linked to better political representation, how parties choose policy positions affects political representation as well. Overall, we conclude that to understand variation in the quality of political representation scholars should look beyond electoral systems and take into account variation in party behavior as well. PMID:29394268

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

Continuous Opinion Dynamics Under Bounded Confidence:. a Survey

NASA Astrophysics Data System (ADS)

Lorenz, Jan

Models of continuous opinion dynamics under bounded confidence have been presented independently by Krause and Hegselmann and by Deffuant et al. in 2000. They have raised a fair amount of attention in the communities of social simulation, sociophysics and complexity science. The researchers working on it come from disciplines such as physics, mathematics, computer science, social psychology and philosophy. In these models agents hold continuous opinions which they can gradually adjust if they hear the opinions of others. The idea of bounded confidence is that agents only interact if they are close in opinion to each other. Usually, the models are analyzed with agent-based simulations in a Monte Carlo style, but they can also be reformulated on the agent's density in the opinion space in a master equation style. The contribution of this survey is fourfold. First, it will present the agent-based and density-based modeling frameworks including the cases of multidimensional opinions and heterogeneous bounds of confidence. Second, it will give the bifurcation diagrams of cluster configuration in the homogeneous model with uniformly distributed initial opinions. Third, it will review the several extensions and the evolving phenomena which have been studied so far, and fourth it will state some open questions.

System of Objectified Judgement Analysis (SOJA) as a tool in rational and transparent drug-decision making.

PubMed

Janknegt, Robert; Scott, Mike; Mairs, Jill; Timoney, Mark; McElnay, James; Brenninkmeijer, Rob

2007-10-01

Drug selection should be a rational process that embraces the principles of evidence-based medicine. However, many factors may affect the choice of agent. It is against this background that the System of Objectified Judgement Analysis (SOJA) process for rational drug-selection was developed. This article describes how the information on which the SOJA process is based, was researched and processed.

Backstepping Design of Adaptive Neural Fault-Tolerant Control for MIMO Nonlinear Systems.

PubMed

Gao, Hui; Song, Yongduan; Wen, Changyun

In this paper, an adaptive controller is developed for a class of multi-input and multioutput nonlinear systems with neural networks (NNs) used as a modeling tool. It is shown that all the signals in the closed-loop system with the proposed adaptive neural controller are globally uniformly bounded for any external input in . In our control design, the upper bound of the NN modeling error and the gains of external disturbance are characterized by unknown upper bounds, which is more rational to establish the stability in the adaptive NN control. Filter-based modification terms are used in the update laws of unknown parameters to improve the transient performance. Finally, fault-tolerant control is developed to accommodate actuator failure. An illustrative example applying the adaptive controller to control a rigid robot arm shows the validation of the proposed controller.In this paper, an adaptive controller is developed for a class of multi-input and multioutput nonlinear systems with neural networks (NNs) used as a modeling tool. It is shown that all the signals in the closed-loop system with the proposed adaptive neural controller are globally uniformly bounded for any external input in . In our control design, the upper bound of the NN modeling error and the gains of external disturbance are characterized by unknown upper bounds, which is more rational to establish the stability in the adaptive NN control. Filter-based modification terms are used in the update laws of unknown parameters to improve the transient performance. Finally, fault-tolerant control is developed to accommodate actuator failure. An illustrative example applying the adaptive controller to control a rigid robot arm shows the validation of the proposed controller.

Regulating Hazardous-materials Transportation with Behavioral Modeling of Drivers

DOT National Transportation Integrated Search

2018-01-29

Changhyun Kwon (ORCID ID 0000-0001-8455-6396) This project considers network regulation problems to minimize the risk of hazmat accidents and potential damages to the environment, while considering bounded rationality of drivers. We consider governme...

Context as Relevance-Driven Abduction and Charitable Satisficing

PubMed Central

Attardo, Salvatore

2016-01-01

It has been widely assumed that the full meaning of a linguistic expression can be grasped only within a situation, the context of the utterance. There is even agreement that certain factors within the situation are particularly significant, including gestures and facial expressions of the participants, their social roles, the setting of the exchange, the objects surrounding the participants, the linguistic, cultural and educational backgrounds of the participants, their beliefs, including those concerning the situation, the social procedures and conventions that regulate the situation. Finally, there is some agreement that context is dynamic, reflexive (the speakers are mutually aware of their beliefs), not limited to linguistics actions, and last but not least, a psychological construct. This definition of context is not (very) controversial, but it leaves out two major problems, which will be addressed in this paper: how is context arrived at? And, since a perfectly natural interpretation of the above definition could be that the context of each utterance is the entire universe, how is the relevant context delimited? Four related concepts will provide the answer to both questions: abductive reasoning, driven by relevance and cooperation, and bounded rationality and the principle of charity. Simply put, context is derived abductively by the speakers assuming that for the speakers to behave the way they behave and do so rationally, a given context must be available to them. The context is bounded by the simple requirement that speakers not try to optimize their interpretation/calculation, but rather satisfice, i.e., find the first acceptable solution and by the need to follow the principle of charity, which forces intersubjective agreement. Thus, abductive reasoning and bounded rationality will be shown to be sufficient to calculate the relevant context of utterances (or other rationality-driven interactions) and to effectively delimit the potentially infinite search space that must be explored to do so. PMID:27014123

Context as Relevance-Driven Abduction and Charitable Satisficing.

PubMed

Attardo, Salvatore

2016-01-01

It has been widely assumed that the full meaning of a linguistic expression can be grasped only within a situation, the context of the utterance. There is even agreement that certain factors within the situation are particularly significant, including gestures and facial expressions of the participants, their social roles, the setting of the exchange, the objects surrounding the participants, the linguistic, cultural and educational backgrounds of the participants, their beliefs, including those concerning the situation, the social procedures and conventions that regulate the situation. Finally, there is some agreement that context is dynamic, reflexive (the speakers are mutually aware of their beliefs), not limited to linguistics actions, and last but not least, a psychological construct. This definition of context is not (very) controversial, but it leaves out two major problems, which will be addressed in this paper: how is context arrived at? And, since a perfectly natural interpretation of the above definition could be that the context of each utterance is the entire universe, how is the relevant context delimited? Four related concepts will provide the answer to both questions: abductive reasoning, driven by relevance and cooperation, and bounded rationality and the principle of charity. Simply put, context is derived abductively by the speakers assuming that for the speakers to behave the way they behave and do so rationally, a given context must be available to them. The context is bounded by the simple requirement that speakers not try to optimize their interpretation/calculation, but rather satisfice, i.e., find the first acceptable solution and by the need to follow the principle of charity, which forces intersubjective agreement. Thus, abductive reasoning and bounded rationality will be shown to be sufficient to calculate the relevant context of utterances (or other rationality-driven interactions) and to effectively delimit the potentially infinite search space that must be explored to do so.

Synthesis of surface bound silver nanoparticles on cellulose fibers using lignin as multi-functional agent.

PubMed

Hu, Sixiao; Hsieh, You-Lo

2015-10-20

Lignin has proven to be highly effective "green" multi-functional binding, complexing and reducing agents for silver cations as well as capping agents for the synthesis of silver nanoparticles on ultra-fine cellulose fibrous membranes. Silver nanoparticles could be synthesized in 10min to be densely distributed and stably bound on the cellulose fiber surfaces at up to 2.9% in mass. Silver nanoparticle increased in sizes from 5 to 100nm and became more polydispersed in size distribution on larger fibers and with longer synthesis time. These cellulose fiber bound silver nanoparticles did not agglomerate under elevated temperatures and showed improved thermal stability. The presence of alkali lignin conferred moderate UV absorbing ability in both UV-B and UV-C regions whereas the bound silver nanoparticles exhibited excellent antibacterial activities toward Escherichia coli. Copyright © 2015 Elsevier Ltd. All rights reserved.

Financial Symmetry and Moods in the Market

PubMed Central

Savona, Roberto; Soumare, Maxence; Andersen, Jørgen Vitting

2015-01-01

This paper studies how certain speculative transitions in financial markets can be ascribed to a symmetry break that happens in the collective decision making. Investors are assumed to be bounded rational, using a limited set of information including past price history and expectation on future dividends. Investment strategies are dynamically changed based on realized returns within a game theoretical scheme with Nash equilibria. In such a setting, markets behave as complex systems whose payoff reflect an intrinsic financial symmetry that guarantees equilibrium in price dynamics (fundamentalist state) until the symmetry is broken leading to bubble or anti-bubble scenarios (speculative state). We model such two-phase transition in a micro-to-macro scheme through a Ginzburg-Landau-based power expansion leading to a market temperature parameter which modulates the state transitions in the market. Via simulations we prove that transitions in the market price dynamics can be phenomenologically explained by the number of traders, the number of strategies and amount of information used by agents, all included in our market temperature parameter. PMID:25856392

Sulfonamide-Based Inhibitors of Aminoglycoside Acetyltransferase Eis Abolish Resistance to Kanamycin in Mycobacterium tuberculosis

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

Garzan, Atefeh; Willby, Melisa J.; Green, Keith D.

A two-drug combination therapy where one drug targets an offending cell and the other targets a resistance mechanism to the first drug is a time-tested, yet underexploited approach to combat or prevent drug resistance. By high-throughput screening, we identified a sulfonamide scaffold that served as a pharmacophore to generate inhibitors of Mycobacterium tuberculosis acetyltransferase Eis, whose upregulation causes resistance to the aminoglycoside (AG) antibiotic kanamycin A (KAN) in Mycobacterium tuberculosis. Rational systematic derivatization of this scaffold to maximize Eis inhibition and abolish the Eis-mediated KAN resistance of M. tuberculosis yielded several highly potent agents. A crystal structure of Eis inmore » complex with one of the most potent inhibitors revealed that the inhibitor bound Eis in the AG-binding pocket held by a conformationally malleable region of Eis (residues 28–37) bearing key hydrophobic residues. These Eis inhibitors are promising leads for preclinical development of innovative AG combination therapies against resistant TB.« less

Financial symmetry and moods in the market.

PubMed

Savona, Roberto; Soumare, Maxence; Andersen, Jørgen Vitting

2015-01-01

This paper studies how certain speculative transitions in financial markets can be ascribed to a symmetry break that happens in the collective decision making. Investors are assumed to be bounded rational, using a limited set of information including past price history and expectation on future dividends. Investment strategies are dynamically changed based on realized returns within a game theoretical scheme with Nash equilibria. In such a setting, markets behave as complex systems whose payoff reflect an intrinsic financial symmetry that guarantees equilibrium in price dynamics (fundamentalist state) until the symmetry is broken leading to bubble or anti-bubble scenarios (speculative state). We model such two-phase transition in a micro-to-macro scheme through a Ginzburg-Landau-based power expansion leading to a market temperature parameter which modulates the state transitions in the market. Via simulations we prove that transitions in the market price dynamics can be phenomenologically explained by the number of traders, the number of strategies and amount of information used by agents, all included in our market temperature parameter.

Additive equivalence in turbulent drag reduction by flexible and rodlike polymers.

PubMed

Benzi, Roberto; Ching, Emily S C; Lo, T S; L'vov, Victor S; Procaccia, Itamar

2005-07-01

We address the additive equivalence discovered by Virk and co-workers: drag reduction affected by flexible and rigid rodlike polymers added to turbulent wall-bounded flows is limited from above by a very similar maximum drag reduction (MDR) asymptote. Considering the equations of motion of rodlike polymers in wall-bounded turbulent ensembles, we show that although the microscopic mechanism of attaining the MDR is very different, the macroscopic theory is isomorphic, rationalizing the interesting experimental observations.

Understanding the Current 30-Year Shipbuilding Plan Through Three Models

DTIC Science & Technology

2014-12-01

to what the Navy can ultimately build in ten years and beyond due to the fact that this plan is revised annually. In a political game this...the game and each one hoping for a different outcome. Though not currently possible with the FY2015 Long Range Plan it is possible to analyze the...to make a choice while the bounded rationality theory acknowledges the limits of human capabilities, knowledge, and capacity. Therefore, bounded

The anatomy of choice: active inference and agency.

PubMed

Friston, Karl; Schwartenbeck, Philipp; Fitzgerald, Thomas; Moutoussis, Michael; Behrens, Timothy; Dolan, Raymond J

2013-01-01

This paper considers agency in the setting of embodied or active inference. In brief, we associate a sense of agency with prior beliefs about action and ask what sorts of beliefs underlie optimal behavior. In particular, we consider prior beliefs that action minimizes the Kullback-Leibler (KL) divergence between desired states and attainable states in the future. This allows one to formulate bounded rationality as approximate Bayesian inference that optimizes a free energy bound on model evidence. We show that constructs like expected utility, exploration bonuses, softmax choice rules and optimism bias emerge as natural consequences of this formulation. Previous accounts of active inference have focused on predictive coding and Bayesian filtering schemes for minimizing free energy. Here, we consider variational Bayes as an alternative scheme that provides formal constraints on the computational anatomy of inference and action-constraints that are remarkably consistent with neuroanatomy. Furthermore, this scheme contextualizes optimal decision theory and economic (utilitarian) formulations as pure inference problems. For example, expected utility theory emerges as a special case of free energy minimization, where the sensitivity or inverse temperature (of softmax functions and quantal response equilibria) has a unique and Bayes-optimal solution-that minimizes free energy. This sensitivity corresponds to the precision of beliefs about behavior, such that attainable goals are afforded a higher precision or confidence. In turn, this means that optimal behavior entails a representation of confidence about outcomes that are under an agent's control.

Believable Social and Emotional Agents.

DTIC Science & Technology

1996-05-01

While building tools to support the creation of believable emotional agents, I had to make a number of important design decisions . Before describing...processing systems, it is difficult to give an artist direct control over the emotion - al aspects of the character. By making these decisions explicit, I hope...Woody on “Cheers”). Believable Agents BELIEVABLE SOCIAL AND EMOTIONAL AGENTS 11 Lesson: We don’t want agent architectures that enforce rationality and

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

Dual Rationality and Deliberative Agents

NASA Astrophysics Data System (ADS)

Debenham, John; Sierra, Carles

Human agents deliberate using models based on reason for only a minute proportion of the decisions that they make. In stark contrast, the deliberation of artificial agents is heavily dominated by formal models based on reason such as game theory, decision theory and logic—despite that fact that formal reasoning will not necessarily lead to superior real-world decisions. Further the Nobel Laureate Friedrich Hayek warns us of the ‘fatal conceit’ in controlling deliberative systems using models based on reason as the particular model chosen will then shape the system’s future and either impede, or eventually destroy, the subtle evolutionary processes that are an integral part of human systems and institutions, and are crucial to their evolution and long-term survival. We describe an architecture for artificial agents that is founded on Hayek’s two rationalities and supports the two forms of deliberation used by mankind.

Forbidding Undesirable Agreements: A Dependence-Based Approach to the Regulation of Multi-agent Systems

NASA Astrophysics Data System (ADS)

Turrini, Paolo; Grossi, Davide; Broersen, Jan; Meyer, John-Jules Ch.

The purpose of this contribution is to set up a language to evaluate the results of concerted action among interdependent agents against predetermined properties that we can recognise as desirable from a deontic point of view. Unlike the standard view of logics to reason about coalitionally rational action, the capacity of a set of agents to take a rational decision will be restricted to what we will call agreements, that can be seen as solution concepts to a dependence structure present in a certain game. The language will identify in concise terms those agreements that act accordingly or disaccordingly with the desirable properties arbitrarily set up in the beginning, and will reveal, by logical reasoning, a variety of structural properties of this type of collective action.

Ethical Dilemmas of Swedish School Leaders: Contrasts and Common Themes

ERIC Educational Resources Information Center

Norberg, Katarina; Johansson, Olof

2007-01-01

Being a skillful school leader presumes the competence to judge the ethical consequences of actions. This implies a need for all school agents to discover and analyze what values are at stake and, in turn, reconcile didactic rationality with ethical rationality. This article aims to explore ethical dilemmas in daily school practice, experienced…

The dangers of euthanasia and dementia: how Kantian thinking might be used to support non-voluntary euthanasia in cases of extreme dementia.

PubMed

Sharp, Robert

2012-06-01

Some writers have argued that a Kantian approach to ethics can be used to justify suicide in cases of extreme dementia, where a patient lacks the rationality required of Kantian moral agents. I worry that this line of thinking may lead to the more extreme claim that euthanasia is a proper Kantian response to severe dementia (and similar afflictions). Such morally treacherous thinking seems to be directly implied by the arguments that lead Dennis Cooley and similar writers to claim that Kant might support suicide. If rationality is the only factor in valuing a human life, then the loss of that rationality (however such loss might be defined) would allow us to use essentially utilitarian thinking in order to support non-voluntary euthanasia, since the patients themselves would no longer be moral agents that demand respect. © 2012 Blackwell Publishing Ltd.

Finite-time consensus for multi-agent systems with globally bounded convergence time under directed communication graphs

NASA Astrophysics Data System (ADS)

Fu, Junjie; Wang, Jin-zhi

2017-09-01

In this paper, we study the finite-time consensus problems with globally bounded convergence time also known as fixed-time consensus problems for multi-agent systems subject to directed communication graphs. Two new distributed control strategies are proposed such that leaderless and leader-follower consensus are achieved with convergence time independent on the initial conditions of the agents. Fixed-time formation generation and formation tracking problems are also solved as the generalizations. Simulation examples are provided to demonstrate the performance of the new controllers.

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.

Modeling Opponents in Adversarial Risk Analysis.

PubMed

Rios Insua, David; Banks, David; Rios, Jesus

2016-04-01

Adversarial risk analysis has been introduced as a framework to deal with risks derived from intentional actions of adversaries. The analysis supports one of the decisionmakers, who must forecast the actions of the other agents. Typically, this forecast must take account of random consequences resulting from the set of selected actions. The solution requires one to model the behavior of the opponents, which entails strategic thinking. The supported agent may face different kinds of opponents, who may use different rationality paradigms, for example, the opponent may behave randomly, or seek a Nash equilibrium, or perform level-k thinking, or use mirroring, or employ prospect theory, among many other possibilities. We describe the appropriate analysis for these situations, and also show how to model the uncertainty about the rationality paradigm used by the opponent through a Bayesian model averaging approach, enabling a fully decision-theoretic solution. We also show how as we observe an opponent's decision behavior, this approach allows learning about the validity of each of the rationality models used to predict his decision by computing the models' (posterior) probabilities, which can be understood as a measure of their validity. We focus on simultaneous decision making by two agents. © 2015 Society for Risk Analysis.

The evolving cobweb of relations among partially rational investors.

PubMed

DeLellis, Pietro; DiMeglio, Anna; Garofalo, Franco; Lo Iudice, Francesco

2017-01-01

To overcome the limitations of neoclassical economics, researchers have leveraged tools of statistical physics to build novel theories. The idea was to elucidate the macroscopic features of financial markets from the interaction of its microscopic constituents, the investors. In this framework, the model of the financial agents has been kept separate from that of their interaction. Here, instead, we explore the possibility of letting the interaction topology emerge from the model of the agents' behavior. Then, we investigate how the emerging cobweb of relationship affects the overall market dynamics. To this aim, we leverage tools from complex systems analysis and nonlinear dynamics, and model the network of mutual influence as the output of a dynamical system describing the edge evolution. In this work, the driver of the link evolution is the relative reputation between possibly coupled agents. The reputation is built differently depending on the extent of rationality of the investors. The continuous edge activation or deactivation induces the emergence of leaders and of peculiar network structures, typical of real influence networks. The subsequent impact on the market dynamics is investigated through extensive numerical simulations in selected scenarios populated by partially rational investors.

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.

Smart social adaptation prevents catastrophic ecological regime shifts in networks of myopic harvesters

NASA Astrophysics Data System (ADS)

Donges, Jonathan; Lucht, Wolfgang; Wiedermann, Marc; Heitzig, Jobst; Kurths, Jürgen

2015-04-01

In the anthropocene, the rise of global social and economic networks with ever increasing connectivity and speed of interactions, e.g., the internet or global financial markets, is a key challenge for sustainable development. The spread of opinions, values or technologies on these networks, in conjunction with the coevolution of the network structures themselves, underlies nexuses of current concern such as anthropogenic climate change, biodiversity loss or global land use change. To isolate and quantitatively study the effects and implications of network dynamics for sustainable development, we propose an agent-based model of information flow on adaptive networks between myopic harvesters that exploit private renewable resources. In this conceptual model of a network of socio-ecological systems, information on management practices flows between agents via boundedly rational imitation depending on the state of the resource stocks involved in an interaction. Agents can also adapt the structure of their social network locally by preferentially connecting to culturally similar agents with identical management practices and, at the same time, disconnecting from culturally dissimilar agents. Investigating in detail the statistical mechanics of this model, we find that an increasing rate of information flow through faster imitation dynamics or growing density of network connectivity leads to a marked increase in the likelihood of environmental resource collapse. However, we show that an optimal rate of social network adaptation can mitigate this negative effect without loss of social cohesion through network fragmentation. Our results highlight that seemingly immaterial network dynamics of spreading opinions or values can be of large relevance for the sustainable management of socio-ecological systems and suggest smartly conservative network adaptation as a strategy for mitigating environmental collapse. Hence, facing the great acceleration, these network dynamics should be more routinely incorporated in standard models of economic development or integrated assessment models used for evaluating anthropogenic climate change.

Pharmacists as agents of change for rational drug therapy.

PubMed

Lipton, H L; Byrns, P J; Soumerai, S B; Chrischilles, E A

1995-01-01

We analyze what is known and unknown about the contribution of the pharmacist as patient educator, physician consultant, and agent to affect patient outcomes in ambulatory settings. The need for pharmacist services is discussed, as are the theoretical underpinnings and quality of the scientific evidence to support their efficacy. The analysis is conducted in the context of a shift in pharmacists' roles from product to patient orientation as well as recent U.S. legislation mandating enhanced pharmacists' roles via drug utilization review for all Medicaid patients. We conclude with a research and action agenda, calling for stronger research designs in evaluating pharmacists' interventions. The shifting paradigm in the pharmacy profession, coupled with the implementation of the Omnibus Budget Reconciliation Act of 1990, provide unique opportunities for rigorous evaluations of pharmacists as agents of change for rational drug therapy.

Incidental Reflector Comparison of Containerized Dry Fire Extinguishing Agents

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

Chapman, Bryan Scott; Wysong, Andrew Russell

This document addresses the incidental reflector reactivity worth of containerized fire extinguishing agents authorized for use in PF-4 at Los Alamos National Laboratory (LANL). The intent of the document is to analyze dry fire extinguishing agent that remains in a container and is not actively being used in a fire emergency. The incidental reflector reactivity worth is determined by comparison to various thicknesses of close fitting water reflection which is commonly used to bound incidental reflectors in criticality safety evaluations. The conclusion is that even in unlimited quantities, when containerized the authorized dry fire extinguishing agents are bound by 0.4more » inches of close fitting water.« less

Emergence of cooperation as a non-equilibrium transition in noisy spatial games

NASA Astrophysics Data System (ADS)

Menon, Shakti N.; Sasidevan, V.; Sinha, Sitabhra

2018-04-01

The emergence of cooperation among selfish agents that have no incentive to cooperate is a non-trivial phenomenon that has long intrigued biologists, social scientists and physicists. The iterated Prisoner's Dilemma (IPD) game provides a natural framework for investigating this phenomenon. Here, agents repeatedly interact with their opponents, and their choice to either cooperate or defect is determined at each round by knowledge of the previous outcomes. The spatial version of IPD, where each agent interacts only with their nearest neighbors on a specified connection topology, has been used to study the evolution of cooperation under conditions of bounded rationality. In this paper we study how the collective behavior that arises from the simultaneous actions of the agents (implemented by synchronous update) is affected by (i) uncertainty, measured as noise intensity K, (ii) the payoff b, quantifying the temptation to defect and (iii) the nature of the underlying connection topology. In particular, we study the phase transitions between states characterized by distinct collective dynamics as the connection topology is gradually altered from a two-dimensional lattice to a random network. This is achieved by rewiring links between agents with a probability p following the small-world network construction paradigm. On crossing a specified threshold value of b, the game switches from being Prisoner's Dilemma, characterized by a unique equilibrium, to Stag Hunt, a well-known coordination game having multiple equilibria. We observe that the system can exhibit three collective states corresponding to a pair of absorbing states (viz., all agents cooperating or defecting) and a fluctuating state characterized by agents switching intermittently between cooperation and defection. As noise and temptation can be interpreted as temperature and an external field respectively, a strong analogy can be drawn between the phase diagrams of such games with that of interacting spin systems. Considering the 3-dimensional p-K-b parameter space allows us to investigate the different phase transitions that occur between these collective states and characterize them using finite-size scaling. We find that the values of the critical exponents depend on the connection topology and are different from the Directed Percolation (DP) universality class.

Against the magnanimous in medical ethics.

PubMed

Kottow, M H

1990-09-01

Supererogatory acts are considered by some to be part of medicine, whereas others accept supererogation to be a gratuitous virtue, to be extolled when present, but not to be demanded. The present paper sides with those contending that medicine is duty-bound to benefit patients and that supererogation/altruism must per definition remain outside and beyond any role-description of the profession. Medical ethics should be bound by rational ethics and steer away from separatist views which grant exclusive privileges but also create excessive demands, way beyond what physicians perform or are willing and able to offer.

Communication: An exact bound on the bridge function in integral equation theories.

PubMed

Kast, Stefan M; Tomazic, Daniel

2012-11-07

We show that the formal solution of the general closure relation occurring in Ornstein-Zernike-type integral equation theories in terms of the Lambert W function leads to an exact relation between the bridge function and correlation functions, most notably to an inequality that bounds possible bridge values. The analytical results are illustrated on the example of the Lennard-Jones fluid for which the exact bridge function is known from computer simulations under various conditions. The inequality has consequences for the development of bridge function models and rationalizes numerical convergence issues.

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

PubMed

Djulbegovic, Benjamin; Elqayam, Shira

2017-10-01

Given that more than 30% of healthcare costs are wasted on inappropriate care, suboptimal care is increasingly connected to the quality of medical decisions. It has been argued that personal decisions are the leading cause of death, and 80% of healthcare expenditures result from physicians' decisions. Therefore, improving healthcare necessitates improving medical decisions, ie, making decisions (more) rational. Drawing on writings from The Great Rationality Debate from the fields of philosophy, economics, and psychology, we identify core ingredients of rationality commonly encountered across various theoretical models. Rationality is typically classified under umbrella of normative (addressing the question how people "should" or "ought to" make their decisions) and descriptive theories of decision-making (which portray how people actually make their decisions). Normative theories of rational thought of relevance to medicine include epistemic theories that direct practice of evidence-based medicine and expected utility theory, which provides the basis for widely used clinical decision analyses. Descriptive theories of rationality of direct relevance to medical decision-making include bounded rationality, argumentative theory of reasoning, adaptive rationality, dual processing model of rationality, regret-based rationality, pragmatic/substantive rationality, and meta-rationality. For the first time, we provide a review of wide range of theories and models of rationality. We showed that what is "rational" behaviour under one rationality theory may be irrational under the other theory. We also showed that context is of paramount importance to rationality and that no one model of rationality can possibly fit all contexts. We suggest that in context-poor situations, such as policy decision-making, normative theories based on expected utility informed by best research evidence may provide the optimal approach to medical decision-making, whereas in the context-rich circumstances other types of rationality, informed by human cognitive architecture and driven by intuition and emotions such as the aim to minimize regret, may provide better solution to the problem at hand. The choice of theory under which we operate is important as it determines both policy and our individual decision-making. © 2017 The Authors Journal of Evaluation in Clinical Practice Published by John Wiley & Sons Ltd.

Imprudent Gastro-protective Approach in Majority of Specialists’ Clinics of a Tertiary Hospital

PubMed Central

Patel, Hardik Rameshbhai

2016-01-01

Introduction One out of four prescriptions in out-patient departments contains a gastro-protective drug (APUD) - PPI/ H2 Blockers/ Antacids/ Ulcer Protective’s. These drugs should be prescribed only when there is a justified indication. To assess the prescriptions of gastro-protective agents for appropriateness and rationality, in a tertiary care hospital setup. Materials and Methods It was a cross-sectional observational study conducted from Aug 2013 to Dec 2013 at OPDs of a Tertiary Care Teaching Hospital, Pune. A total of 260 prescriptions containing gastro-protective agents were analysed for appropriateness and rationality. Rationality of drug use was assessed by referring to standard textbooks and guidelines. Cost difference data was analysed by Wilcoxon signed rank test using GraphPad Prism 6. Results Most common class of gastro-protective agents was Proton pump inhibitors (PPIs)-73.77% (Pantoprazole & Dexrabeprazole). Only 37.3% prescriptions had an adequate indication for these drugs {GI prophylaxis (29.6%) and Acid Peptic Disease treatment (7.7%)}. Two irrational Fixed dose combinations found in the study were PPI with prokinetic agent (n=65) and Proton Pump Inhibitor + NSAID combination (n=2). Formulation, spelling and strength errors were found with 75 prescribed drugs. Medication instructions were lacking with most of the drugs. Drug interactions with co-prescribed drugs could be anticipated in 79 cases. Injudicious use of anti-peptic ulcer agents significantly increased the cost of prescriptions (p<0.0001). Conclusion Anti-ulcer drugs are overenthusiastically prescribed by all specialties which can predispose to adverse effects, drug interactions, increased cost and even erroneous prescriptions. PMID:27134889

The concept of rational suicide.

PubMed

Mayo, D J

1986-05-01

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

Emerging Perspectives on Planning and Change Processes.

ERIC Educational Resources Information Center

Beach, Robert H.

1993-01-01

During the past 50 years, educational planning has evolved into a recognized, somewhat esoteric field of study. The four major planning models are rationalism (comprehensive and bounded), incrementalism (or muddling through), mixed or environmental scanning, and goal-free (developmental) planning. Sound educational planning is people-oriented and…

The anatomy of choice: active inference and agency

PubMed Central

Friston, Karl; Schwartenbeck, Philipp; FitzGerald, Thomas; Moutoussis, Michael; Behrens, Timothy; Dolan, Raymond J.

2013-01-01

This paper considers agency in the setting of embodied or active inference. In brief, we associate a sense of agency with prior beliefs about action and ask what sorts of beliefs underlie optimal behavior. In particular, we consider prior beliefs that action minimizes the Kullback–Leibler (KL) divergence between desired states and attainable states in the future. This allows one to formulate bounded rationality as approximate Bayesian inference that optimizes a free energy bound on model evidence. We show that constructs like expected utility, exploration bonuses, softmax choice rules and optimism bias emerge as natural consequences of this formulation. Previous accounts of active inference have focused on predictive coding and Bayesian filtering schemes for minimizing free energy. Here, we consider variational Bayes as an alternative scheme that provides formal constraints on the computational anatomy of inference and action—constraints that are remarkably consistent with neuroanatomy. Furthermore, this scheme contextualizes optimal decision theory and economic (utilitarian) formulations as pure inference problems. For example, expected utility theory emerges as a special case of free energy minimization, where the sensitivity or inverse temperature (of softmax functions and quantal response equilibria) has a unique and Bayes-optimal solution—that minimizes free energy. This sensitivity corresponds to the precision of beliefs about behavior, such that attainable goals are afforded a higher precision or confidence. In turn, this means that optimal behavior entails a representation of confidence about outcomes that are under an agent's control. PMID:24093015

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

PubMed Central

Elqayam, Shira

2017-01-01

Abstract Given that more than 30% of healthcare costs are wasted on inappropriate care, suboptimal care is increasingly connected to the quality of medical decisions. It has been argued that personal decisions are the leading cause of death, and 80% of healthcare expenditures result from physicians' decisions. Therefore, improving healthcare necessitates improving medical decisions, ie, making decisions (more) rational. Drawing on writings from The Great Rationality Debate from the fields of philosophy, economics, and psychology, we identify core ingredients of rationality commonly encountered across various theoretical models. Rationality is typically classified under umbrella of normative (addressing the question how people “should” or “ought to” make their decisions) and descriptive theories of decision‐making (which portray how people actually make their decisions). Normative theories of rational thought of relevance to medicine include epistemic theories that direct practice of evidence‐based medicine and expected utility theory, which provides the basis for widely used clinical decision analyses. Descriptive theories of rationality of direct relevance to medical decision‐making include bounded rationality, argumentative theory of reasoning, adaptive rationality, dual processing model of rationality, regret‐based rationality, pragmatic/substantive rationality, and meta‐rationality. For the first time, we provide a review of wide range of theories and models of rationality. We showed that what is “rational” behaviour under one rationality theory may be irrational under the other theory. We also showed that context is of paramount importance to rationality and that no one model of rationality can possibly fit all contexts. We suggest that in context‐poor situations, such as policy decision‐making, normative theories based on expected utility informed by best research evidence may provide the optimal approach to medical decision‐making, whereas in the context‐rich circumstances other types of rationality, informed by human cognitive architecture and driven by intuition and emotions such as the aim to minimize regret, may provide better solution to the problem at hand. The choice of theory under which we operate is important as it determines both policy and our individual decision‐making. PMID:28730671

Diversity of rationality affects the evolution of cooperation

NASA Astrophysics Data System (ADS)

Chen, Yu-Zhong; Huang, Zi-Gang; Wang, Sheng-Jun; Zhang, Yan; Wang, Ying-Hai

2009-05-01

By modifying the Fermi updating rule, we present the diversity of individual rationality to the evolutionary prisoner’s dilemma game, and our results shows that this diversity heavily influences the evolution of cooperation. Cluster-forming mechanism of cooperators can either be highly enhanced or severely deteriorated by different distributions of rationality. Slight change in the rationality distribution may transfer the whole system from the global absorbing state of cooperators to that of defectors. Based on mean-field argument, quantitative analysis of the stability of cooperative clusters reveals the critical role played by agents with moderate degree values in the evolution of the whole system. The inspiration from our work may provide us a deeper comprehension toward some social phenomena.

Kodiak: An Implementation Framework for Branch and Bound Algorithms

NASA Technical Reports Server (NTRS)

Smith, Andrew P.; Munoz, Cesar A.; Narkawicz, Anthony J.; Markevicius, Mantas

2015-01-01

Recursive branch and bound algorithms are often used to refine and isolate solutions to several classes of global optimization problems. A rigorous computation framework for the solution of systems of equations and inequalities involving nonlinear real arithmetic over hyper-rectangular variable and parameter domains is presented. It is derived from a generic branch and bound algorithm that has been formally verified, and utilizes self-validating enclosure methods, namely interval arithmetic and, for polynomials and rational functions, Bernstein expansion. Since bounds computed by these enclosure methods are sound, this approach may be used reliably in software verification tools. Advantage is taken of the partial derivatives of the constraint functions involved in the system, firstly to reduce the branching factor by the use of bisection heuristics and secondly to permit the computation of bifurcation sets for systems of ordinary differential equations. The associated software development, Kodiak, is presented, along with examples of three different branch and bound problem types it implements.

Problems of Change: Bounded Rationality--What do Teachers Really Do?

ERIC Educational Resources Information Center

Hatcher, Catherine W.

Through an integration of teacher effectiveness and reading research, this paper proposes ways for improving classroom reading instruction. The first part of the paper reviews teacher effectiveness research, noting the shifts that have occurred in that area from the early efforts, which focused on identifying and describing teacher characteristics…

Estimating the Volumes of Solid Figures with Curved Surfaces.

ERIC Educational Resources Information Center

Cohen, Donald

1991-01-01

Several examples of solid figures that calculus students can use to exercise their skills at estimating volume are presented. Although these figures are bounded by surfaces that are portions of regular cylinders, it is interesting to note that their volumes can be expressed as rational numbers. (JJK)

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.

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.

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2015-12-01

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

Balancing the stability and the catalytic specificities of OP hydrolases with enhanced V-agent activities.

PubMed

Reeves, T E; Wales, M E; Grimsley, J K; Li, P; Cerasoli, D M; Wild, J R

2008-06-01

Rational site-directed mutagenesis and biophysical analyses have been used to explore the thermodynamic stability and catalytic capabilities of organophosphorus hydrolase (OPH) and its genetically modified variants. There are clear trade-offs in the stability of modifications that enhance catalytic activities. For example, the H254R/H257L variant has higher turnover numbers for the chemical warfare agents VX (144 versus 14 s(-1) for the native enzyme (wild type) and VR (Russian VX, 465 versus 12 s(-1) for wild type). These increases are accompanied by a loss in stability in which the total Gibb's free energy for unfolding is 19.6 kcal/mol, which is 5.7 kcal/mol less than that of the wild-type enzyme. X-ray crystallographic studies support biophysical data that suggest amino acid residues near the active site contribute to the chemical and thermal stability through hydrophobic and cation-pi interactions. The cation-pi interactions appear to contribute an additional 7 kcal/mol to the overall global stability of the enzyme. Using rational design, it has been possible to make amino acid changes in this region that restored the stability, yet maintained effective V-agent activities, with turnover numbers of 68 and 36 s(-1) for VX and VR, respectively. This study describes the first rationally designed, stability/activity balance for an OPH enzyme with a legitimate V-agent activity, and its crystal structure.

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

PubMed

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

2013-05-18

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

Reasoning about instrumental and communicative agency in human infancy.

PubMed

Gergely, György; Jacob, Pierre

2012-01-01

Theoretical rationality and practical rationality are, respectively, properties of an individual's belief system and decision system. While reasoning about instrumental actions complies with practical rationality, understanding communicative actions complies with the principle of relevance. Section 2 reviews the evidence showing that young infants can reason about an agent's instrumental action by representing her subjective motivations and the episodic contents of her epistemic states (including false beliefs). Section 3 reviews the evidence showing special sensitivity in young human infants to some ostensive behavioral signals encoding an agent's communicative intention. We also address the puzzle of imitative learning of novel means actions by 1-year olds and argue that it can be resolved only by assuming that the infant construes the model's demonstration as a communicative, not an instrumental, action. Section 4 reviews the evidence for natural pedagogy, a species-unique social communicative learning mechanism that exploits human infants' receptivity to ostensive-communicative signals and enables infants to acquire kind-wide generalizations from the nonverbal demonstrations of communicative agents. We argue that the essentialist bias that has been shown to be involved in children's concepts of natural kinds also applies to infants' concepts of artifacts. We further examine how natural pedagogy may also boost inductive learning in human infancy.

Content modification attacks on consensus seeking multi-agent system with double-integrator dynamics.

PubMed

Dong, Yimeng; Gupta, Nirupam; Chopra, Nikhil

2016-11-01

In this paper, vulnerability of a distributed consensus seeking multi-agent system (MAS) with double-integrator dynamics against edge-bound content modification cyber attacks is studied. In particular, we define a specific edge-bound content modification cyber attack called malignant content modification attack (MCoMA), which results in unbounded growth of an appropriately defined group disagreement vector. Properties of MCoMA are utilized to design detection and mitigation algorithms so as to impart resilience in the considered MAS against MCoMA. Additionally, the proposed detection mechanism is extended to detect the general edge-bound content modification attacks (not just MCoMA). Finally, the efficacies of the proposed results are illustrated through numerical simulations.

Content modification attacks on consensus seeking multi-agent system with double-integrator dynamics

NASA Astrophysics Data System (ADS)

Dong, Yimeng; Gupta, Nirupam; Chopra, Nikhil

2016-11-01

In this paper, vulnerability of a distributed consensus seeking multi-agent system (MAS) with double-integrator dynamics against edge-bound content modification cyber attacks is studied. In particular, we define a specific edge-bound content modification cyber attack called malignant content modification attack (MCoMA), which results in unbounded growth of an appropriately defined group disagreement vector. Properties of MCoMA are utilized to design detection and mitigation algorithms so as to impart resilience in the considered MAS against MCoMA. Additionally, the proposed detection mechanism is extended to detect the general edge-bound content modification attacks (not just MCoMA). Finally, the efficacies of the proposed results are illustrated through numerical simulations.

[Rational drug use: an economic approach to decision making].

PubMed

Mota, Daniel Marques; da Silva, Marcelo Gurgel Carlos; Sudo, Elisa Cazue; Ortún, Vicente

2008-04-01

The present article approaches rational drug use (RDU) from the economical point of view. The implementation of RDU implies in costs and involves acquisition of knowledge and behavioral changes of several agents. The difficulties in implementing RDU may be due to shortage problems, information asymmetry, lack of information, uncertain clinical decisions, externalities, time-price, incentives for drug prescribers and dispensers, drug prescriber preferences and marginal utility. Health authorities, among other agencies, must therefore regularize, rationalize and control drug use to minimize inefficiency in pharmaceutical care and to prevent exposing the population to unnecessary health risks.

Against the magnanimous in medical ethics.

PubMed Central

Kottow, M H

1990-01-01

Supererogatory acts are considered by some to be part of medicine, whereas others accept supererogation to be a gratuitous virtue, to be extolled when present, but not to be demanded. The present paper sides with those contending that medicine is duty-bound to benefit patients and that supererogation/altruism must per definition remain outside and beyond any role-description of the profession. Medical ethics should be bound by rational ethics and steer away from separatist views which grant exclusive privileges but also create excessive demands, way beyond what physicians perform or are willing and able to offer. PMID:2231634

Runge-Lenz vector, accidental SU(2) symmetry, and unusual multiplets for motion on a cone

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

Al-Hashimi, M.H.; Wiese, U.-J.

2008-01-15

We consider a particle moving on a cone and bound to its tip by 1/r or harmonic oscillator potentials. When the deficit angle of the cone divided by 2{pi} is a rational number, all bound classical orbits are closed. Correspondingly, the quantum system has accidental degeneracies in the discrete energy spectrum. An accidental SU(2) symmetry is generated by the rotations around the tip of the cone as well as by a Runge-Lenz vector. Remarkably, some of the corresponding multiplets have fractional 'spin' and unusual degeneracies.

Vancomycin-modified Fe3O4@SiO2@Ag microflowers as effective antimicrobial agents.

PubMed

Wang, Chongwen; Zhang, Kehan; Zhou, Zhe; Li, Qingjun; Shao, Liting; Hao, Rong Zhang; Xiao, Rui; Wang, Shengqi

2017-01-01

Nanomaterials combined with antibiotics exhibit synergistic effects and have gained increasing interest as promising antimicrobial agents. In this study, vancomycin-modified magnetic-based silver microflowers (Van/Fe 3 O 4 @SiO 2 @Ag microflowers) were rationally designed and prepared to achieve strong bactericidal ability, a wide antimicrobial spectrum, and good recyclability. High-performance Fe 3 O 4 @SiO 2 @Ag microflowers served as a multifunction-supporting matrix and exhibited sufficient magnetic response property due to their 200 nm Fe 3 O 4 core. The microflowers also possessed a highly branched flower-like Ag shell that provided a large surface area for effective Ag ion release and bacterial contact. The modified-vancomycin layer was effectively bound to the cell wall of bacteria to increase the permeability of the cell membrane and facilitate the entry of the Ag ions into the bacterium, resulting in cell death. As such, the fabricated Van/Fe 3 O 4 @SiO 2 @Ag microflowers were predicted to be an effective and environment-friendly antibacterial agent. This hypothesis was verified through sterilization of Gram-negative Escherichia coli and Gram-positive methicillin-resistant Staphylococcus aureus , with minimum inhibitory concentrations of 10 and 20 μg mL -1 , respectively. The microflowers also showed enhanced effect compared with bare Fe 3 O 4 @SiO 2 @Ag microflowers and free-form vancomycin, confirming the synergistic effects of the combination of the two components. Moreover, the antimicrobial effect was maintained at more than 90% after five cycling assays, indicating the high stability of the product. These findings reveal that Van/Fe 3 O 4 @SiO 2 @Ag microflowers exhibit promising applications in the antibacterial fields.

Vancomycin-modified Fe3O4@SiO2@Ag microflowers as effective antimicrobial agents

PubMed Central

Wang, Chongwen; Zhang, Kehan; Zhou, Zhe; Li, Qingjun; Shao, Liting; Hao, Rong Zhang; Xiao, Rui; Wang, Shengqi

2017-01-01

Nanomaterials combined with antibiotics exhibit synergistic effects and have gained increasing interest as promising antimicrobial agents. In this study, vancomycin-modified magnetic-based silver microflowers (Van/Fe3O4@SiO2@Ag microflowers) were rationally designed and prepared to achieve strong bactericidal ability, a wide antimicrobial spectrum, and good recyclability. High-performance Fe3O4@SiO2@Ag microflowers served as a multifunction-supporting matrix and exhibited sufficient magnetic response property due to their 200 nm Fe3O4 core. The microflowers also possessed a highly branched flower-like Ag shell that provided a large surface area for effective Ag ion release and bacterial contact. The modified-vancomycin layer was effectively bound to the cell wall of bacteria to increase the permeability of the cell membrane and facilitate the entry of the Ag ions into the bacterium, resulting in cell death. As such, the fabricated Van/Fe3O4@SiO2@Ag microflowers were predicted to be an effective and environment-friendly antibacterial agent. This hypothesis was verified through sterilization of Gram-negative Escherichia coli and Gram-positive methicillin-resistant Staphylococcus aureus, with minimum inhibitory concentrations of 10 and 20 μg mL−1, respectively. The microflowers also showed enhanced effect compared with bare Fe3O4@SiO2@Ag microflowers and free-form vancomycin, confirming the synergistic effects of the combination of the two components. Moreover, the antimicrobial effect was maintained at more than 90% after five cycling assays, indicating the high stability of the product. These findings reveal that Van/Fe3O4@SiO2@Ag microflowers exhibit promising applications in the antibacterial fields. PMID:28450783

Tipping Points towards Regional Forest or Urban Transition in Stressed Rural Areas: An Agent-based Modelling Application of Socio-Economic Shifts in Rural Vermont US

NASA Astrophysics Data System (ADS)

Tsai, Y.; Turnbull, S.; Zia, A.

2015-12-01

In rural areas where farming competes with urban development and environmental amenities, urban and forest transitions occur simultaneously at different locales with different rates due to the underlying socio-economic shifts. Here we develop an interactive land use transition agent-based model (ILUTABM) in which farmers' land use decisions are made contingent on expansion and location choices of urban businesses and urban residences, as well as farmers' perceived ecosystem services produced by their land holdings. The ILUTABM simulates heterogeneity in land use decisions at parcel levels by differentiating decision making processes for agricultural and urban landowners. Landowners are simulated to make land-use transition decisions as bounded rational agents that maximize their partial expected utility functions under different underlying socio-economic conditions given the category of a landowner and the spatial characteristics of the landowner's landholdings. The ILUTABM is parameterized by spatial data sets such as National Land Cover Database (NLCD), zoning, parcels, property prices, US census, farmers surveys, building/facility characteristics, soil, slope and elevation. We then apply the ILUTABM to the rural Vermont landscape, located in the Northeast Arm District of Lake Champlain and the downstream sub-watersheds of Missisquoi River, to generate phase transitions of rural land towards urban land near peri-urban areas and towards forest land near financially stressed farmlands during 2001-2051. Possible tipping point trajectories of rural land towards regional forest or urban transition are simulated under three socio-economic scenarios: business as usual (ILUTABM calibrated to 2011 NLCD), increased incentives for conservation easements, and increased incentives for attracting urban residences and businesses.

Reversed enantioselectivity of diisopropyl fluorophosphatase against organophosphorus nerve agents by rational design.

PubMed

Melzer, Marco; Chen, Julian C-H; Heidenreich, Anne; Gäb, Jürgen; Koller, Marianne; Kehe, Kai; Blum, Marc-Michael

2009-12-02

Diisopropyl fluorophosphatase (DFPase) from Loligo vulgaris is an efficient and robust biocatalyst for the hydrolysis of a range of highly toxic organophosphorus compounds including the nerve agents sarin, soman, and cyclosarin. In contrast to the substrate diisopropyl fluorophosphate (DFP) the nerve agents possess an asymmetric phosphorus atom, which leads to pairs of enantiomers that display markedly different toxicities. Wild-type DFPase prefers the less toxic stereoisomers of the substrates which leads to slower detoxification despite rapid hydrolysis. Enzyme engineering efforts based on rational design yielded two quadruple enzyme mutants with reversed enantioselectivity and overall enhanced activity against tested nerve agents. The reversed stereochemical preference is explained through modeling studies and the crystal structures of the two mutants. Using the engineered mutants in combination with wild-type DFPase leads to significantly enhanced activity and detoxification, which is especially important for personal decontamination. Our findings may also be of relevance for the structurally related enzyme human paraoxonase (PON), which is of considerable interest as a potential catalytic in vivo scavenger in case of organophosphorus poisoning.

Modelling body weight, dieting and obesity traps

NASA Astrophysics Data System (ADS)

Barbieri, Paolo Nicola

2017-02-01

This paper presents a theoretical investigation into why losing weight is so difficult even in the absence of rational addiction, time-inconsistent preferences or bounded rationality. We add to the existing literature by focusing on the role that individual metabolism has on weight loss. The results from the theoretical model provide multiple steady states and a threshold revealing a situation of "obesity traps" that the individual must surpass in order to successfully lose weight. Any weight-loss efforts that the individual undertakes have to surpass such threshold in order to result in permanent weight loss, otherwise the individual will gradually regain weight and converge to his or her previous body weight.

Tuning the properties of conjugated polyelectrolytes and application in a biosensor platform

DOEpatents

Chen, Liaohai

2004-05-18

The present invention provides a method of detecting a biological agent including contacting a sample with a sensor including a polymer system capable of having an alterable measurable property from the group of luminescence, anisotropy, redox potential and uv/vis absorption, the polymer system including an ionic conjugated polymer and an electronically inert polyelectrolyte having a biological agent recognition element bound thereto, the electronically inert polyelectrolyte adapted for undergoing a conformational structural change upon exposure to a biological agent having affinity for binding to the recognition element bound to the electronically inert polyelectrolyte, and, detecting the detectable change in the alterable measurable property. A chemical moiety being the reaction product of (i) a polyelectrolyte monomer and (ii) a biological agent recognition element-substituted polyelectrolyte monomer is also provided.

A Perspective on Judgment and Choice: Mapping Bounded Rationality

ERIC Educational Resources Information Center

Kahneman, Daniel

2003-01-01

Early studies of intuitive judgment and decision making conducted with the late Amos Tversky are reviewed in the context of two related concepts: an analysis of accessibility, the ease with which thoughts come to mind; a distinction between effortless intuition and deliberate reasoning. Intuitive thoughts, like percepts, are highly accessible.…

Benzothiophene inhibitors of MK2. Part 2: Improvements in kinase selectivity and cell potency

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

Anderson, David R.; Meyers, Marvin J.; Kurumbail, Ravi G.

2010-10-01

Optimization of kinase selectivity for a set of benzothiophene MK2 inhibitors provided analogs with potencies of less than 500 nM in a cell based assay. The selectivity of the inhibitors can be rationalized by examination of X-ray crystal structures of inhibitors bound to MK2.

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…

Barriers to Energy Efficiency and the Uptake of Green Revolving Funds in Canadian Universities

ERIC Educational Resources Information Center

Maiorano, John; Savan, Beth

2015-01-01

Purpose: The purpose of this paper is to investigate the barriers to the implementation of energy efficiency projects in Canadian universities, including access to capital, bounded rationality, hidden costs, imperfect information, risk and split incentives. Methods to address these barriers are investigated, including evaluating the efficacy of…

The College-Choice Process of High Achieving Freshmen: A Comparative Case Study

ERIC Educational Resources Information Center

Dale, Amanda

2010-01-01

The purpose of this study was to examine the college-choice process of high achieving students. Employing current literature and previous research, it combined current models of college choice and the influential factors identified throughout the literature while utilizing the concept of bounded rationality to create a conceptual framework to…

A Hybrid Trust-Based Recommender System for Online Communities of Practice

ERIC Educational Resources Information Center

Zheng, Xiao-Lin; Chen, Chao-Chao; Hung, Jui-Long; He, Wu; Hong, Fu-Xing; Lin, Zhen

2015-01-01

The needs for life-long learning and the rapid development of information technologies promote the development of various types of online Community of Practices (CoPs). In online CoPs, bounded rationality and metacognition are two major issues, especially when learners face information overload and there is no knowledge authority within the…

A mechanism for social selection and successful altruism.

PubMed

Simon, H A

1990-12-21

Within the framework of neo-Darwinism, with its focus on fitness, it has been hard to account for altruism behavior that reduces the fitness of the altruist but increases average fitness in society. Many population biologists argue that, except for altruism to close relatives, human behavior that appears to be altruistic amounts to reciprocal altruism, behavior undertaken with an expectation of reciprocation, hence incurring no net cost to fitness. Herein is proposed a simple and robust mechanism, based on human docility and bounded rationality that can account for the evolutionary success of genuinely altruistic behavior. Because docility-receptivity to social influence-contributes greatly to fitness in the human species, it will be positively selected. As a consequence, society can impose a "tax" on the gross benefits gained by individuals from docility by inducing docile individuals to engage in altruistic behaviors. Limits on rationality in the face of environmental complexity prevent the individual from avoiding this "tax." An upper bound is imposed on altruism by the condition that there must remain a net fitness advantage for docile behavior after the cost to the individual of altruism has been deducted.

[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.

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.

Consumer Search, Rationing Rules, and the Consequence for Competition

NASA Astrophysics Data System (ADS)

Ruebeck, Christopher S.

Firms' conjectures about demand are consequential in oligopoly games. Through agent-based modeling of consumers' search for products, we can study the rationing of demand between capacity-constrained firms offering homogeneous products and explore the robustness of analytically solvable models' results. After algorithmically formalizing short-run search behavior rather than assuming a long-run average, this study predicts stronger competition in a two-stage capacity-price game.

Betting on the outcomes of measurements: a Bayesian theory of quantum probability

NASA Astrophysics Data System (ADS)

Pitowsky, Itamar

We develop a systematic approach to quantum probability as a theory of rational betting in quantum gambles. In these games of chance, the agent is betting in advance on the outcomes of several (finitely many) incompatible measurements. One of the measurements is subsequently chosen and performed and the money placed on the other measurements is returned to the agent. We show how the rules of rational betting imply all the interesting features of quantum probability, even in such finite gambles. These include the uncertainty principle and the violation of Bell's inequality among others. Quantum gambles are closely related to quantum logic and provide a new semantics for it. We conclude with a philosophical discussion on the interpretation of quantum mechanics.

Stock markets as Minority Games: cognitive heterogeneity and equilibrium emergence

NASA Astrophysics Data System (ADS)

Brandouy, O.

2005-04-01

Standard finance theory generally assumes homogeneous agents relatively to their preferences, heuristics and investment strategies. We propose to study, in an agent-based simulation, the emergence of equilibrium under various heterogeneous conditions. Market interaction is stylized with the Minority Game representation. It is shown that inductive rational equilibrium emerges even though agents do not share the same representations of the value. This may lead to consider again the roots of EMH and REH.

The neural basis of belief updating and rational decision making

PubMed Central

Achtziger, Anja; Hügelschäfer, Sabine; Steinhauser, Marco

2014-01-01

Rational decision making under uncertainty requires forming beliefs that integrate prior and new information through Bayes’ rule. Human decision makers typically deviate from Bayesian updating by either overweighting the prior (conservatism) or overweighting new information (e.g. the representativeness heuristic). We investigated these deviations through measurements of electrocortical activity in the human brain during incentivized probability-updating tasks and found evidence of extremely early commitment to boundedly rational heuristics. Participants who overweight new information display a lower sensibility to conflict detection, captured by an event-related potential (the N2) observed around 260 ms after the presentation of new information. Conservative decision makers (who overweight prior probabilities) make up their mind before new information is presented, as indicated by the lateralized readiness potential in the brain. That is, they do not inhibit the processing of new information but rather immediately rely on the prior for making a decision. PMID:22956673

The neural basis of belief updating and rational decision making.

PubMed

Achtziger, Anja; Alós-Ferrer, Carlos; Hügelschäfer, Sabine; Steinhauser, Marco

2014-01-01

Rational decision making under uncertainty requires forming beliefs that integrate prior and new information through Bayes' rule. Human decision makers typically deviate from Bayesian updating by either overweighting the prior (conservatism) or overweighting new information (e.g. the representativeness heuristic). We investigated these deviations through measurements of electrocortical activity in the human brain during incentivized probability-updating tasks and found evidence of extremely early commitment to boundedly rational heuristics. Participants who overweight new information display a lower sensibility to conflict detection, captured by an event-related potential (the N2) observed around 260 ms after the presentation of new information. Conservative decision makers (who overweight prior probabilities) make up their mind before new information is presented, as indicated by the lateralized readiness potential in the brain. That is, they do not inhibit the processing of new information but rather immediately rely on the prior for making a decision.

Continuous punishment and the potential of gentle rule enforcement.

PubMed

Erev, Ido; Ingram, Paul; Raz, Ornit; Shany, Dror

2010-05-01

The paper explores the conditions that determine the effect of rule enforcement policies that imply an attempt to punish all the visible violations of the rule. We start with a simple game-theoretic analysis that highlights the value of gentle COntinuous Punishment (gentle COP) policies. If the subjects of the rule are rational, gentle COP can eliminate violations even when the rule enforcer has limited resources. The second part of the paper uses simulations to examine the robustness of gentle COP policies to likely deviations from rationality. The results suggest that when the probability of detecting violations is sufficiently high, gentle COP policies can be effective even when the subjects of the rule are boundedly rational adaptive learners. The paper concludes with experimental studies that clarify the value of gentle COP policies in the lab, and in attempt to eliminate cheating in exams. Copyright (c) 2009 Elsevier B.V. All rights reserved.

Crystal structure of checkpoint kinase 2 in complex with NSC 109555, a potent and selective inhibitor

PubMed Central

Lountos, George T; Tropea, Joseph E; Zhang, Di; Jobson, Andrew G; Pommier, Yves; Shoemaker, Robert H; Waugh, David S

2009-01-01

Checkpoint kinase 2 (Chk2), a ser/thr kinase involved in the ATM-Chk2 checkpoint pathway, is activated by genomic instability and DNA damage and results in either arrest of the cell cycle to allow DNA repair to occur or apoptosis if the DNA damage is severe. Drugs that specifically target Chk2 could be beneficial when administered in combination with current DNA-damaging agents used in cancer therapy. Recently, a novel inhibitor of Chk2, NSC 109555, was identified that exhibited high potency (IC50 = 240 nM) and selectivity. This compound represents a new chemotype and lead for the development of novel Chk2 inhibitors that could be used as therapeutic agents for the treatment of cancer. To facilitate the discovery of new analogs of NSC 109555 with even greater potency and selectivity, we have solved the crystal structure of this inhibitor in complex with the catalytic domain of Chk2. The structure confirms that the compound is an ATP-competitive inhibitor, as the electron density clearly reveals that it occupies the ATP-binding pocket. However, the mode of inhibition differs from that of the previously studied structure of Chk2 in complex with debromohymenialdisine, a compound that inhibits both Chk1 and Chk2. A unique hydrophobic pocket in Chk2, located very close to the bound inhibitor, presents an opportunity for the rational design of compounds with higher binding affinity and greater selectivity. PMID:19177354

Physical characteristics of lanthanide complexes that act as magnetization transfer (MT) contrast agents

NASA Astrophysics Data System (ADS)

Zhang, Shanrong; Sherry, A. Dean

2003-02-01

Rapid water exchange is normally considered a prerequisite for efficient Gd3+-based MRI contrast agents. Yet recent measures of exchange rates in some Gd3+ complexes have shown that water exchange can become limiting when such complexes are attached to larger macromolecular structures. A new class of lanthanide complexes that display unusually slow water exchange (bound water lifetimes (τM298) > 10 μs) has recently been reported. This apparent disadvantage may be taken advantage of by switching the metal ion from gadolinium(III) to a lanthanide that shifts the bound water resonance substantially away from bulk water. Given appropriate water exchange kinetics, one can then alter the intensity of the bulk water signal by selective presaturation of this highly shifted, Ln3+-bound water resonance. This provides the basis of a new method to alter MR image contrast in tissue. We have synthesized a variety of DOTA-tetra(amide) ligands to evaluate as potential magnetization transfer (MT) contrast agents and found that the bound water lifetimes in these complexes are sensitive to both ligand structure (a series of Eu3+ complexes have τM298 values that range from 1 to 1300 μs) and the identity of the paramagnetic Ln3+ cation (from 3 to 800 μs for a single ligand). This demonstrates that it may be possible either to fine-tune the ligand structure or to select proper lanthanide cation to create an optimal MT agent for any clinical imaging field.

Learning What to Want: Context-Sensitive Preference Learning

PubMed Central

Srivastava, Nisheeth; Schrater, Paul

2015-01-01

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

Out of Bounds

ERIC Educational Resources Information Center

Davis, Noah

2007-01-01

Due to improper contact between agents and players as well as agent infractions that have occurred and hit universities, states and colleges are increasingly turning to the courts to help protect the integrity of big-time college athletics. Universities such as Oregon now hold "agent days" to educate players about appropriate conduct. States are…

Better with Byzantine: Manipulation-Optimal Mechanisms

NASA Astrophysics Data System (ADS)

Othman, Abraham; Sandholm, Tuomas

A mechanism is manipulable if it is in some agents’ best interest to misrepresent their private information. The revelation principle establishes that, roughly, anything that can be accomplished by a manipulable mechanism can also be accomplished with a truthful mechanism. Yet agents often fail to play their optimal manipulations due to computational limitations or various flavors of incompetence and cognitive biases. Thus, manipulable mechanisms in particular should anticipate byzantine play. We study manipulation-optimal mechanisms: mechanisms that are undominated by truthful mechanisms when agents act fully rationally, and do better than any truthful mechanism if any agent fails to act rationally in any way. This enables the mechanism designer to do better than the revelation principle would suggest, and obviates the need to predict byzantine agents’ irrational behavior. We prove a host of possibility and impossibility results for the concept which have the impression of broadly limiting possibility. These results are largely in line with the revelation principle, although the considerations are more subtle and the impossibility not universal.

The prisoner’s dilemma on co-evolving networks under perfect rationality

NASA Astrophysics Data System (ADS)

Biely, Christoly; Dragosits, Klaus; Thurner, Stefan

2007-04-01

We consider the prisoner’s dilemma being played repeatedly on a dynamic network, where agents may choose their actions as well as their co-players. This leads to co-evolution of network structure and strategy patterns of the players. Individual decisions are made fully rationally and are based on local information only. They are made such that links to defecting agents are resolved and that cooperating agents build up new links. The exact form of the updating scheme is motivated by profit maximization and not by imitation. If players update their decisions in a synchronized way the system exhibits oscillatory dynamics: Periods of growing cooperation (and total linkage) alternate with periods of increasing defection. The cyclical behavior is reduced and the system stabilizes at significant total cooperation levels when players are less synchronized. In this regime we find emergent network structures resembling ‘complex’ and hierarchical topology. The exponent of the power-law degree distribution ( γ∼8.6) perfectly matches empirical results for human communication networks.

One-pot synthesis of MWW zeolite nanosheets using a rationally designed organic structure-directing agent

DOE PAGES

Luo, Helen Y.; Michaelis, Vladimir K.; Hodges, Sydney; ...

2015-07-22

A new material MIT-1 comprised of delaminated MWW zeolite nanosheets is synthesized in one-pot using a rationally designed organic structure-directing agent (OSDA). The OSDA is comprised of a hydrophilic head segment that resembles the OSDA used to synthesize the zeolite precursor MCM22(P), a hydrophobic tail segment that resembles the swelling agent used to swell MCM22(P), and a di-quaternary ammonium linker that connects both segments. MIT-1 features high crystallinity and surface areas exceeding 500 m 2g -1, and can be synthesized over a wide synthesis window that includes Si/Al ratios ranging from 13 to 67. Characterization data reveal high mesoporosity andmore » acid strength with no detectable amorphous silica phases. In conclusion, compared to MCM-22 and MCM-56, MIT-1 shows a three-fold increase in catalytic activity for the Friedel-Crafts alkylation of benzene with benzyl alcohol.« less

On the Psychology of the Recognition Heuristic: Retrieval Primacy as a Key Determinant of Its Use

ERIC Educational Resources Information Center

Pachur, Thorsten; Hertwig, Ralph

2006-01-01

The recognition heuristic is a prime example of a boundedly rational mind tool that rests on an evolved capacity, recognition, and exploits environmental structures. When originally proposed, it was conjectured that no other probabilistic cue reverses the recognition-based inference (D. G. Goldstein & G. Gigerenzer, 2002). More recent studies…

Teaching as Goal-Less and Reflective Design: A Conversation with Herbert A. Simon and Donald Schon

ERIC Educational Resources Information Center

Go, Johnny C.

2012-01-01

This paper examines Donald Schon's critique of Herbert Simon's "science of design" to determine whether later developments in Simon's thought--particularly, his theories of "bounded rationality" and "goal-less designing"--can contribute to an appreciation of Schon's notion of reflective practice. The paper then argues, that viewed through the…

Fluency Heuristic: A Model of How the Mind Exploits a By-Product of Information Retrieval

ERIC Educational Resources Information Center

Hertwig, Ralph; Herzog, Stefan M.; Schooler, Lael J.; Reimer, Torsten

2008-01-01

Boundedly rational heuristics for inference can be surprisingly accurate and frugal for several reasons. They can exploit environmental structures, co-opt complex capacities, and elude effortful search by exploiting information that automatically arrives on the mental stage. The fluency heuristic is a prime example of a heuristic that makes the…

Rational discovery of dengue type 2 non-competitive inhibitors.

PubMed

Heh, Choon H; Othman, Rozana; Buckle, Michael J C; Sharifuddin, Yusrizam; Yusof, Rohana; Rahman, Noorsaadah A

2013-07-01

Various works have been carried out in developing therapeutics against dengue. However, to date, no effective vaccine or anti-dengue agent has yet been discovered. The development of protease inhibitors is considered as a promising option, but most previous works have involved competitive inhibition. In this study, we focused on rational discovery of potential anti-dengue agents based on non-competitive inhibition of DEN-2 NS2B/NS3 protease. A homology model of the DEN-2 NS2B/NS3 protease (using West Nile Virus NS2B/NS3 protease complex, 2FP7, as the template) was used as the target, and pinostrobin, a flavanone, was used as the standard ligand. Virtual screening was performed involving a total of 13 341 small compounds, with the backbone structures of chalcone, flavanone, and flavone, available in the ZINC database. Ranking of the resulting compounds yielded compounds with higher binding affinities compared with the standard ligand. Inhibition assay of the selected top-ranking compounds against DEN-2 NS2B/NS3 proteolytic activity resulted in significantly better inhibition compared with the standard and correlated well with in silico results. In conclusion, via this rational discovery technique, better inhibitors were identified. This method can be used in further work to discover lead compounds for anti-dengue agents. © 2013 John Wiley & Sons A/S.

Perceived Animacy Influences the Processing of Human-Like Surface Features in the Fusiform Gyrus

PubMed Central

Shultz, Sarah; McCarthya, Gregory

2014-01-01

While decades of research have demonstrated that a region of the right fusiform gyrus (FG) responds selectively to faces, a second line of research suggests that the FG responds to a range of animacy cues, including biological motion and goal-directed actions, even in the absence of faces or other human-like surface features. These findings raise the question of whether the FG is indeed sensitive to faces or to the more abstract category of animate agents. The current study uses fMRI to examine whether the FG responds to all faces in a category-specific way or whether the FG is especially sensitive to the faces of animate agents. Animate agents are defined here as intentional agents with the capacity for rational goal-directed actions. Specifically, we examine how the FG responds to an entity that looks like an animate agent but that lacks the capacity for goal-directed, rational action. Region-of-interest analyses reveal that the FG activates more strongly to the animate compared with the inanimate entity, even though the surface features of both animate and inanimate entities were identical. These results suggest that the FG does not respond to all faces in a category-specific way, and is instead especially sensitive to whether an entity is animate. PMID:24905285

New Hardness Results for Diophantine Approximation

NASA Astrophysics Data System (ADS)

Eisenbrand, Friedrich; Rothvoß, Thomas

We revisit simultaneous Diophantine approximation, a classical problem from the geometry of numbers which has many applications in algorithms and complexity. The input to the decision version of this problem consists of a rational vector α ∈ ℚ n , an error bound ɛ and a denominator bound N ∈ ℕ + . One has to decide whether there exists an integer, called the denominator Q with 1 ≤ Q ≤ N such that the distance of each number Q ·α i to its nearest integer is bounded by ɛ. Lagarias has shown that this problem is NP-complete and optimization versions have been shown to be hard to approximate within a factor n c/ loglogn for some constant c > 0. We strengthen the existing hardness results and show that the optimization problem of finding the smallest denominator Q ∈ ℕ + such that the distances of Q·α i to the nearest integer are bounded by ɛ is hard to approximate within a factor 2 n unless {textrm{P}} = NP.

Quadrature formula for evaluating left bounded Hadamard type hypersingular integrals

NASA Astrophysics Data System (ADS)

Bichi, Sirajo Lawan; Eshkuvatov, Z. K.; Nik Long, N. M. A.; Okhunov, Abdurahim

2014-12-01

Left semi-bounded Hadamard type Hypersingular integral (HSI) of the form H(h,x) = 1/π √{1+x/1-x }∫-1 **1√{1-t/1+t }h(t)/(t-x)2 dt,x∈(-1.1), Where h(t) is a smooth function is considered. The automatic quadrature scheme (AQS) is constructed by approximating the density function h(t) by the truncated Chebyshev polynomials of the fourth kind. Numerical results revealed that the proposed AQS is highly accurate when h(t) is choosing to be the polynomial and rational functions. The results are in line with the theoretical findings.

The effect of chemical agents on the turnover of the bound phosphate associated with the sodium-and-potassium ion-stimulated adenosine triphosphatase in ox brain microsomes

PubMed Central

Rodnight, R.

1970-01-01

1. The effect of chemical agents on the turnover of the Na+-dependent bound phosphate and the simultaneous Na+-dependent hydrolysis of ATP by a membrane preparation from ox brain was studied at an ATP/protein ratio of 12.5pmol/μg. 2. The agents were added immediately after phosphorylation of the preparation in a medium containing 50mm-sodium chloride and 2.5μm-[γ-32P]ATP. 3. Concentrations of sodium chloride above 150mm, calcium chloride to 20mm and suramin to 1.4mm inhibited both phosphorylation and dephosphorylation and concomitantly slowed ATP hydrolysis. At 125mm-sodium chloride dephosphorylation and hydrolysis were slightly slowed without affecting phosphorylation. 4. Ethanol to 1.6m concentration inhibited dephosphorylation without affecting phosphorylation; the bound phosphate was increased and ATP hydrolysis slowed. 5. Ouabain to 4mm concentration partially inhibited ATP hydrolysis and caused a transient (1–2s) rise in bound phosphate followed by a rapid fall to a lower plateau value, which eventually declined to zero by the time ATP hydrolysis was complete. 6. Of the detergents examined Lubrol W, Triton X-100 and sodium deoxycholate had no significant effect on turnover. Sodium dodecyl sulphate and sodium decyl sulphate to 3.5mm and 20mm respectively completely inhibited turnover and ATP hydrolysis and stabilized the bound phosphate. PMID:4250238

Advancing cancer drug discovery towards more agile development of targeted combination therapies.

PubMed

Carragher, Neil O; Unciti-Broceta, Asier; Cameron, David A

2012-01-01

Current drug-discovery strategies are typically 'target-centric' and are based upon high-throughput screening of large chemical libraries against nominated targets and a selection of lead compounds with optimized 'on-target' potency and selectivity profiles. However, high attrition of targeted agents in clinical development suggest that combinations of targeted agents will be most effective in treating solid tumors if the biological networks that permit cancer cells to subvert monotherapies are identified and retargeted. Conventional drug-discovery and development strategies are suboptimal for the rational design and development of novel drug combinations. In this article, we highlight a series of emerging technologies supporting a less reductionist, more agile, drug-discovery and development approach for the rational design, validation, prioritization and clinical development of novel drug combinations.

Constant Price of Anarchy in Network Creation Games via Public Service Advertising

NASA Astrophysics Data System (ADS)

Demaine, Erik D.; Zadimoghaddam, Morteza

Network creation games have been studied in many different settings recently. These games are motivated by social networks in which selfish agents want to construct a connection graph among themselves. Each node wants to minimize its average or maximum distance to the others, without paying much to construct the network. Many generalizations have been considered, including non-uniform interests between nodes, general graphs of allowable edges, bounded budget agents, etc. In all of these settings, there is no known constant bound on the price of anarchy. In fact, in many cases, the price of anarchy can be very large, namely, a constant power of the number of agents. This means that we have no control on the behavior of network when agents act selfishly. On the other hand, the price of stability in all these models is constant, which means that there is chance that agents act selfishly and we end up with a reasonable social cost.

Commanding and Controlling Satellite Clusters (IEEE Intelligent Systems, November/December 2000)

DTIC Science & Technology

2000-01-01

real - time operating system , a message-passing OS well suited for distributed...ground Flight processors ObjectAgent RTOS SCL RTOS RDMS Space command language Real - time operating system Rational database management system TS-21 RDMS...engineer with Princeton Satellite Systems. She is working with others to develop ObjectAgent software to run on the OSE Real Time Operating System .

A New Consequence of Simpson's Paradox: Stable Cooperation in One-Shot Prisoner's Dilemma from Populations of Individualistic Learners

ERIC Educational Resources Information Center

Chater, Nick; Vlaev, Ivo; Grinberg, Maurice

2008-01-01

Theories of choice in economics typically assume that interacting agents act individualistically and maximize their own utility. Specifically, game theory proposes that rational players should defect in one-shot prisoners' dilemmas (PD). Defection also appears to be the inevitable outcome for agents who learn by reinforcement of past choices,…

Collagen solubility correlates with skin optical clearing.

PubMed

Hirshburg, Jason; Choi, Bernard; Nelson, J Stuart; Yeh, Alvin T

2006-01-01

Biomedical optics and photomedicine applications are challenged by the turbidity of most biological tissue systems. Nonreactive, biocompatible chemical agents can induce a reversible reduction in optical scattering of collagenous tissues such as human skin. Herein we show that a chemical agent's tissue optical clearing potential is directly related to its collagen solubility, providing a rational design basis for effective, percutaneous formulations.

Persuasion Model and Its Evaluation Based on Positive Change Degree of Agent Emotion

NASA Astrophysics Data System (ADS)

Jinghua, Wu; Wenguang, Lu; Hailiang, Meng

For it can meet needs of negotiation among organizations take place in different time and place, and for it can make its course more rationality and result more ideal, persuasion based on agent can improve cooperation among organizations well. Integrated emotion change in agent persuasion can further bring agent advantage of artificial intelligence into play. Emotion of agent persuasion is classified, and the concept of positive change degree is given. Based on this, persuasion model based on positive change degree of agent emotion is constructed, which is explained clearly through an example. Finally, the method of relative evaluation is given, which is also verified through a calculation example.

Rational and mechanistic perspectives on reinforcement learning.

PubMed

Chater, Nick

2009-12-01

This special issue describes important recent developments in applying reinforcement learning models to capture neural and cognitive function. But reinforcement learning, as a theoretical framework, can apply at two very different levels of description: mechanistic and rational. Reinforcement learning is often viewed in mechanistic terms--as describing the operation of aspects of an agent's cognitive and neural machinery. Yet it can also be viewed as a rational level of description, specifically, as describing a class of methods for learning from experience, using minimal background knowledge. This paper considers how rational and mechanistic perspectives differ, and what types of evidence distinguish between them. Reinforcement learning research in the cognitive and brain sciences is often implicitly committed to the mechanistic interpretation. Here the opposite view is put forward: that accounts of reinforcement learning should apply at the rational level, unless there is strong evidence for a mechanistic interpretation. Implications of this viewpoint for reinforcement-based theories in the cognitive and brain sciences are discussed.

Application of Asymmetric Flow Field-Flow Fractionation hyphenations for liposome-antimicrobial peptide interaction.

PubMed

Iavicoli, Patrizia; Urbán, Patricia; Bella, Angelo; Ryadnov, Maxim G; Rossi, François; Calzolai, Luigi

2015-11-27

Asymmetric Flow Field-Flow Fractionation (AF4) combined with multidetector analysis form a promising technique in the field of nanoparticle characterization. This system is able to measure the dimensions and physicochemical properties of nanoparticles with unprecedented accuracy and precision. Here, for the first time, this technique is optimized to characterize the interaction between an archetypal antimicrobial peptide and synthetic membranes. By using charged and neutral liposomes it is possible to mimic some of the charge characteristics of biological membranes. The use of AF4 system allows determining, in a single analysis, information regarding the selectivity of the peptides, the quantity of peptides bound to each liposome, the induced change in the size distribution and morphology of the liposomes. The results obtained provide relevant information for the study of structure-activity relationships in the context of membrane-induced antimicrobial action. This information will contribute to the rational design of potent antimicrobial agents in the future. Moreover, the application of this method to other liposome systems is straightforward and would be extremely useful for a comprehensive characterization with regard to size distribution and protein interaction in the nanomedicine field. Copyright © 2015. Published by Elsevier B.V.

Dynamics of bounded confidence opinion in heterogeneous social networks: Concord against partial antagonism

NASA Astrophysics Data System (ADS)

Kurmyshev, Evguenii; Juárez, Héctor A.; González-Silva, Ricardo A.

2011-08-01

Bounded confidence models of opinion dynamics in social networks have been actively studied in recent years, in particular, opinion formation and extremism propagation along with other aspects of social dynamics. In this work, after an analysis of limitations of the Deffuant-Weisbuch (DW) bounded confidence, relative agreement model, we propose the mixed model that takes into account two psychological types of individuals. Concord agents (C-agents) are friendly people; they interact in a way that their opinions always get closer. Agents of the other psychological type show partial antagonism in their interaction (PA-agents). Opinion dynamics in heterogeneous social groups, consisting of agents of the two types, was studied on different social networks: Erdös-Rényi random graphs, small-world networks and complete graphs. Limit cases of the mixed model, pure C- and PA-societies, were also studied. We found that group opinion formation is, qualitatively, almost independent of the topology of networks used in this work. Opinion fragmentation, polarization and consensus are observed in the mixed model at different proportions of PA- and C-agents, depending on the value of initial opinion tolerance of agents. As for the opinion formation and arising of “dissidents”, the opinion dynamics of the C-agents society was found to be similar to that of the DW model, except for the rate of opinion convergence. Nevertheless, mixed societies showed dynamics and bifurcation patterns notably different to those of the DW model. The influence of biased initial conditions over opinion formation in heterogeneous social groups was also studied versus the initial value of opinion uncertainty, varying the proportion of the PA- to C-agents. Bifurcation diagrams showed an impressive evolution of collective opinion, in particular, radical changes of left to right consensus or vice versa at an opinion uncertainty value equal to 0.7 in the model with the PA/C mixture of population near 50/50.

Discovery of a small-molecule HIV-1 integrase inhibitor-binding site | Center for Cancer Research

Cancer.gov

The lowest energy-binding conformation of an inhibitor bound to the dimeric interface of HIV-1 integrase core domain. The yellow region represents a unique allosteric binding site identified by affinity labeling and mass spectrometry and validated through mutagenesis. This site can provide a potential platform for the rational design of inhibitors selective for disruption of

Stochastic Evolution Dynamic of the Rock-Scissors-Paper Game Based on a Quasi Birth and Death Process

NASA Astrophysics Data System (ADS)

Yu, Qian; Fang, Debin; Zhang, Xiaoling; Jin, Chen; Ren, Qiyu

2016-06-01

Stochasticity plays an important role in the evolutionary dynamic of cyclic dominance within a finite population. To investigate the stochastic evolution process of the behaviour of bounded rational individuals, we model the Rock-Scissors-Paper (RSP) game as a finite, state dependent Quasi Birth and Death (QBD) process. We assume that bounded rational players can adjust their strategies by imitating the successful strategy according to the payoffs of the last round of the game, and then analyse the limiting distribution of the QBD process for the game stochastic evolutionary dynamic. The numerical experiments results are exhibited as pseudo colour ternary heat maps. Comparisons of these diagrams shows that the convergence property of long run equilibrium of the RSP game in populations depends on population size and the parameter of the payoff matrix and noise factor. The long run equilibrium is asymptotically stable, neutrally stable and unstable respectively according to the normalised parameters in the payoff matrix. Moreover, the results show that the distribution probability becomes more concentrated with a larger population size. This indicates that increasing the population size also increases the convergence speed of the stochastic evolution process while simultaneously reducing the influence of the noise factor.

Stochastic Evolution Dynamic of the Rock-Scissors-Paper Game Based on a Quasi Birth and Death Process.

PubMed

Yu, Qian; Fang, Debin; Zhang, Xiaoling; Jin, Chen; Ren, Qiyu

2016-06-27

Stochasticity plays an important role in the evolutionary dynamic of cyclic dominance within a finite population. To investigate the stochastic evolution process of the behaviour of bounded rational individuals, we model the Rock-Scissors-Paper (RSP) game as a finite, state dependent Quasi Birth and Death (QBD) process. We assume that bounded rational players can adjust their strategies by imitating the successful strategy according to the payoffs of the last round of the game, and then analyse the limiting distribution of the QBD process for the game stochastic evolutionary dynamic. The numerical experiments results are exhibited as pseudo colour ternary heat maps. Comparisons of these diagrams shows that the convergence property of long run equilibrium of the RSP game in populations depends on population size and the parameter of the payoff matrix and noise factor. The long run equilibrium is asymptotically stable, neutrally stable and unstable respectively according to the normalised parameters in the payoff matrix. Moreover, the results show that the distribution probability becomes more concentrated with a larger population size. This indicates that increasing the population size also increases the convergence speed of the stochastic evolution process while simultaneously reducing the influence of the noise factor.

Endogenous Market-Clearing Prices and Reference Point Adaptation

NASA Astrophysics Data System (ADS)

Dragicevic, Arnaud Z.

When prices depend on the submitted bids, i.e. with endogenous market-clearing prices in repeated-round auction mechanisms, the assumption of independent private values that underlines the property of incentive-compatibility is to be brought into question; even if these mechanisms provide active involvement and market learning. In its orthodox view, adaptive bidding behavior imperils incentive-compatibility. We relax the assumption of private values' independence in the repeated-round auctions, when the market-clearing prices are made public at the end of each round. Instead of using game-theory learning models, we introduce a behavioral model that shows that bidders bid according to the anchoring-and-adjustment heuristic, which neither ignores the rationality and incentive-compatibility constraints, nor rejects the posted prices issued from others' bids. Bidders simply weight information at their disposal and adjust their discovered value using reference points encoded in the sequential price weighting function. Our model says that bidders and offerers are sincere boundedly rational utility maximizers. It lies between evolutionary dynamics and adaptive heuristics and we model the concept of inertia as high weighting of the anchor, which stands for truthful bidding and high regard to freshly discovered preferences. Adjustment means adaptive rule based on adaptation of the reference point in the direction of the posted price. It helps a bidder to maximize her expected payoff, which is after all the only purpose that matters to rationality. The two components simply suggest that sincere bidders are boundedly rational. Furthermore, by deviating from their anchor in the direction of the public signal, bidders operate in a correlated equilibrium. The correlation between bids comes from the commonly observed history of play and each bidder's actions are determined by the history. Bidders are sincere if they have limited memory and confine their reference point adaptation to their anchor and the latest posted price. S-shaped weighting mechanism reflects such a bidding strategy.

Comparative effectiveness research as choice architecture: the behavioral law and economics solution to the health care cost crisis.

PubMed

Korobkin, Russell

2014-02-01

With the Patient Protection and Affordable Care Act ("ACA") set to dramatically increase access to medical care, the problem of rising costs will move center stage in health law and policy discussions. "Consumer directed health care" proposals, which provide patients with financial incentives to equate marginal costs and benefits of care at the point of treatment, demand more decisionmaking ability from consumers than is plausible due to bounded rationality. Proposals that seek to change the incentives of health care providers threaten to create conflicts of interest between doctors and patients. New approaches are desperately needed. This Article proposes a government-facilitated but market-based approach to improving efficiency in the private market for medical care that I call "relative value health insurance." This approach focuses on the "choice architecture" necessary to enable even boundedly rational patients to contract for an efficient level of health care services through their health insurance purchase decisions. It uses comparative effectiveness research, which the ACA funds at a significant level for the first time, to rate medical treatments on a scale of one to ten based on their relative value, taking into account expected costs and benefits. These relative value ratings would enable consumers to contract with insurers for different levels of medical care at different prices, reflecting different cost-quality trade-offs. The Article describes both the benefits of relative value health insurance and the impediments to its implementation. It concludes with a brief discussion of how relative value ratings could also help to rationalize expenditures on public health insurance programs.

Hybrid learning in signalling games

NASA Astrophysics Data System (ADS)

Barrett, Jeffrey A.; Cochran, Calvin T.; Huttegger, Simon; Fujiwara, Naoki

2017-09-01

Lewis-Skyrms signalling games have been studied under a variety of low-rationality learning dynamics. Reinforcement dynamics are stable but slow and prone to evolving suboptimal signalling conventions. A low-inertia trial-and-error dynamical like win-stay/lose-randomise is fast and reliable at finding perfect signalling conventions but unstable in the context of noise or agent error. Here we consider a low-rationality hybrid of reinforcement and win-stay/lose-randomise learning that exhibits the virtues of both. This hybrid dynamics is reliable, stable and exceptionally fast.

Zero-point energy effects in anion solvation shells.

PubMed

Habershon, Scott

2014-05-21

By comparing classical and quantum-mechanical (path-integral-based) molecular simulations of solvated halide anions X(-) [X = F, Cl, Br and I], we identify an ion-specific quantum contribution to anion-water hydrogen-bond dynamics; this effect has not been identified in previous simulation studies. For anions such as fluoride, which strongly bind water molecules in the first solvation shell, quantum simulations exhibit hydrogen-bond dynamics nearly 40% faster than the corresponding classical results, whereas those anions which form a weakly bound solvation shell, such as iodide, exhibit a quantum effect of around 10%. This observation can be rationalized by considering the different zero-point energy (ZPE) of the water vibrational modes in the first solvation shell; for strongly binding anions, the ZPE of bound water molecules is larger, giving rise to faster dynamics in quantum simulations. These results are consistent with experimental investigations of anion-bound water vibrational and reorientational motion.

Game theory in models of pedestrian room evacuation

NASA Astrophysics Data System (ADS)

Bouzat, S.; Kuperman, M. N.

2014-03-01

We analyze the pedestrian evacuation of a rectangular room with a single door considering a lattice gas scheme with the addition of behavioral aspects of the pedestrians. The movement of the individuals is based on random and rational choices and is affected by conflicts between two or more agents that want to advance to the same position. Such conflicts are solved according to certain rules closely related to the concept of strategies in game theory, cooperation and defection. We consider game rules analogous to those from the Prisoner's Dilemma and Stag Hunt games, with payoffs associated to the probabilities of the individuals to advance to the selected site. We find that, even when defecting is the rational choice for any agent, under certain conditions, cooperators can take advantage from mutual cooperation and leave the room more rapidly than defectors.

Game theory in models of pedestrian room evacuation.

PubMed

Bouzat, S; Kuperman, M N

2014-03-01

We analyze the pedestrian evacuation of a rectangular room with a single door considering a lattice gas scheme with the addition of behavioral aspects of the pedestrians. The movement of the individuals is based on random and rational choices and is affected by conflicts between two or more agents that want to advance to the same position. Such conflicts are solved according to certain rules closely related to the concept of strategies in game theory, cooperation and defection. We consider game rules analogous to those from the Prisoner's Dilemma and Stag Hunt games, with payoffs associated to the probabilities of the individuals to advance to the selected site. We find that, even when defecting is the rational choice for any agent, under certain conditions, cooperators can take advantage from mutual cooperation and leave the room more rapidly than defectors.

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.

Role of Humic-Bound Iron as an Electron Transfer Agent in Dissimilatory Fe(III) Reduction

PubMed Central

Lovley, Derek R.; Blunt-Harris, Elizabeth L.

1999-01-01

The dissimilatory Fe(III) reducer Geobacter metallireducens reduced Fe(III) bound in humic substances, but the concentrations of Fe(III) in a wide range of highly purified humic substances were too low to account for a significant portion of the electron-accepting capacities of the humic substances. Furthermore, once reduced, the iron in humic substances could not transfer electrons to Fe(III) oxide. These results suggest that other electron-accepting moieties in humic substances, such as quinones, are the important electron-accepting and shuttling agents under Fe(III)-reducing conditions. PMID:10473447

Distributed Synchronization Control of Multiagent Systems With Unknown Nonlinearities.

PubMed

Su, Shize; Lin, Zongli; Garcia, Alfredo

2016-01-01

This paper revisits the distributed adaptive control problem for synchronization of multiagent systems where the dynamics of the agents are nonlinear, nonidentical, unknown, and subject to external disturbances. Two communication topologies, represented, respectively, by a fixed strongly-connected directed graph and by a switching connected undirected graph, are considered. Under both of these communication topologies, we use distributed neural networks to approximate the uncertain dynamics. Decentralized adaptive control protocols are then constructed to solve the cooperative tracker problem, the problem of synchronization of all follower agents to a leader agent. In particular, we show that, under the proposed decentralized control protocols, the synchronization errors are ultimately bounded, and their ultimate bounds can be reduced arbitrarily by choosing the control parameter appropriately. Simulation study verifies the effectiveness of our proposed protocols.

More Fair Play in an Ultimatum Game after Resettlement in Zimbabwe: A Field Experiment and a Structural Model

PubMed Central

Kohler, Stefan

2013-01-01

Zimbabwean villagers of distinct background have resettled in government-organized land reforms for more than three decades. Against this backdrop, I assess the level of social cohesion in some of the newly established communities by estimating the average preferences for fairness in a structural model of bounded rationality. The estimations are based on behavioral data from an ultimatum game field experiment played by 234 randomly selected households in 6 traditional and 14 resettled villages almost two decades after resettlement. Equal or higher degrees of fairness are estimated in all resettlement schemes. In one, or arguably two, out of three distinct resettlement schemes studied, the resettled villagers exhibit significantly higher degrees of fairness ( ) and rationality ( ) than those who live in traditional villages. Overall, villagers appear similarly rational, but the attitude toward fairness is significantly stronger in resettled communities ( ). These findings are consistent with the idea of an increased need for cooperation required in recommencement. PMID:23724095

More fair play in an ultimatum game after resettlement in Zimbabwe: a field experiment and a structural model.

PubMed

Kohler, Stefan

2013-01-01

Zimbabwean villagers of distinct background have resettled in government-organized land reforms for more than three decades. Against this backdrop, I assess the level of social cohesion in some of the newly established communities by estimating the average preferences for fairness in a structural model of bounded rationality. The estimations are based on behavioral data from an ultimatum game field experiment played by 234 randomly selected households in 6 traditional and 14 resettled villages almost two decades after resettlement. Equal or higher degrees of fairness are estimated in all resettlement schemes. In one, or arguably two, out of three distinct resettlement schemes studied, the resettled villagers exhibit significantly higher degrees of fairness (p ≤ 0.11) and rationality (p ≤ 0.04) than those who live in traditional villages. Overall, villagers appear similarly rational, but the attitude toward fairness is significantly stronger in resettled communities (p ≤ 0.01). These findings are consistent with the idea of an increased need for cooperation required in recommencement.

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

A DESCRIPTION OF HANKEL OPERATORS OF CLASS \\mathfrak{S}_p FOR p>0, AN INVESTIGATION OF THE RATE OF RATIONAL APPROXIMATION, AND OTHER APPLICATIONS

NASA Astrophysics Data System (ADS)

Peller, V. V.

1985-02-01

The main result is the following description of Hankel operators in the Schatten-von Neumann class \\mathfrak{S}_p when 0: \\displaystyle \\Gamma_\\varphi\\in\\mathfrak{S}_p\\Leftrightarrow \\varphi\\in B_p^{1/p},where \\Gamma_\\varphi is the Hankel operator with symbol \\varphi, and B_p^{1/p} is the Besov class. This result extends results obtained earlier for 1\\leqslant p<+\\infty by the author to the case 0. Also described are the Hankel operators in the Schatten-Lorentz classes \\mathfrak{S}_{pq}, 0, 0. Precise descriptions of classes of functions defined in terms of rational approximation in the bounded mean oscillation norm are given as an application, along with a complete investigation of the case where the decrease is of power order, and some precise results on rational approximation in the L^\\infty-norm. Certain other applications are also considered.Bibliography: 57 titles.

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.

An analytic study on bounds for the associated Legendre functions. [for truncation of geopotential series in spherical harmonics in orbital analyses

NASA Technical Reports Server (NTRS)

Payne, M. H.

1973-01-01

The bounds for the normalized associated Legendre functions P sub nm were studied to provide a rational basis for the truncation of the geopotential series in spherical harmonics in various orbital analyses. The conjecture is made that the largest maximum of the normalized associated Legendre function lies in the interval which indicates the greatest integer function. A procedure is developed for verifying this conjecture. An on-line algebraic manipulator, IAM, is used to implement the procedure and the verification is carried out for all n equal to or less than 2m, for m = 1 through 6. A rigorous proof of the conjecture is not available.

Development of a scale to assess Hwa-Byung, a Korean culture-bound syndrome, using the Korean MMPI-2.

PubMed

Roberts, Miguel E; Han, Kyunghee; Weed, Nathan C

2006-09-01

This study documents the development of an MMPI-2 scale designed to assess features of the Korean culture-bound syndrome, Hwa-Byung (HB). An American research team and psychiatric practitioners in Korea created an 18-item HB scale via rational item selection and psycho-metric refinement. Principal components analysis of scale items revealed four components, reflecting content domains of general health, gastrointestinal symptoms, hopelessness, and anger. This four-component solution applied well to both Korean men and women, but not to an American sample. Although some findings were encouraging, future studies employing clinical samples are needed to provide further validation of this scale.

The evolving cobweb of relations among partially rational investors

PubMed Central

DiMeglio, Anna; Garofalo, Franco; Lo Iudice, Francesco

2017-01-01

To overcome the limitations of neoclassical economics, researchers have leveraged tools of statistical physics to build novel theories. The idea was to elucidate the macroscopic features of financial markets from the interaction of its microscopic constituents, the investors. In this framework, the model of the financial agents has been kept separate from that of their interaction. Here, instead, we explore the possibility of letting the interaction topology emerge from the model of the agents’ behavior. Then, we investigate how the emerging cobweb of relationship affects the overall market dynamics. To this aim, we leverage tools from complex systems analysis and nonlinear dynamics, and model the network of mutual influence as the output of a dynamical system describing the edge evolution. In this work, the driver of the link evolution is the relative reputation between possibly coupled agents. The reputation is built differently depending on the extent of rationality of the investors. The continuous edge activation or deactivation induces the emergence of leaders and of peculiar network structures, typical of real influence networks. The subsequent impact on the market dynamics is investigated through extensive numerical simulations in selected scenarios populated by partially rational investors. PMID:28196144

What matters when judging intentionality-moral content or normative status? Testing the rational scientist model of the side-effect.

PubMed

Papadopoulos, C; Hayes, B K

2018-06-01

Previous work has demonstrated a "side-effect effect," such that intentionality is more likely to be attributed to agents who bring about negatively valenced as opposed to positively valenced side effects. The rational-scientist model explains this by suggesting that norm-violating side effects are more informative for inferring intentionality than norm-conforming side effects. In the present study we reexamined this account, addressing limitations of previous empirical tests (e.g., Uttich & Lombrozo, Cognition 116: 87-100, 2010). Side-effect valence and norm status were manipulated factorially, enabling an examination of the impact of norm status on intentionality judgments in both positively and negatively valenced side effects. Additionally, the impact of side-effect norm status on the perceived valences of side effects and agents was examined. Effects of norm status were found for both positive and negative side effects. Violation of an ostensibly neutral norm led to negative perceptions of the side effect. However, a norm status effect on intentionality judgments persisted when these effects were controlled. These results support the view that the side-effect effect is the result of the rational use of social-cognitive evidence.

Rational Discovery of (+) (S) Abscisic Acid as a Potential Antifungal Agent: a Repurposing Approach.

PubMed

Khedr, Mohammed A; Massarotti, Alberto; Mohamed, Maged E

2018-06-04

Fungal infections are spreading widely worldwide, and the types of treatment are limited due to the lack of diverse therapeutic agents and their associated side effects and toxicity. The discovery of new antifungal classes is vital and critical. We discovered the antifungal activity of abscisic acid through a rational drug design methodology that included the building of homology models for fungal chorismate mutases and a pharmacophore model derived from a transition state inhibitor. Ligand-based virtual screening resulted in some hits that were filtered using molecular docking and molecular dynamic simulations studies. Both in silico methods and in vitro antifungal assays were used as tools to select and validate the abscisic acid repurposing. Abscisic acid inhibition assays confirmed the inhibitory effect of abscisic acid on chorismate mutase through the inhibition of phenylpyruvate production. The repositioning of abscisic acid, the well-known and naturally occurring plant growth regulator, as a potential antifungal agent because of its suggested action as an inhibitor to several fungal chorismate mutases was the main result of this work.

Cosmographic analysis with Chebyshev polynomials

NASA Astrophysics Data System (ADS)

Capozziello, Salvatore; D'Agostino, Rocco; Luongo, Orlando

2018-05-01

The limits of standard cosmography are here revised addressing the problem of error propagation during statistical analyses. To do so, we propose the use of Chebyshev polynomials to parametrize cosmic distances. In particular, we demonstrate that building up rational Chebyshev polynomials significantly reduces error propagations with respect to standard Taylor series. This technique provides unbiased estimations of the cosmographic parameters and performs significatively better than previous numerical approximations. To figure this out, we compare rational Chebyshev polynomials with Padé series. In addition, we theoretically evaluate the convergence radius of (1,1) Chebyshev rational polynomial and we compare it with the convergence radii of Taylor and Padé approximations. We thus focus on regions in which convergence of Chebyshev rational functions is better than standard approaches. With this recipe, as high-redshift data are employed, rational Chebyshev polynomials remain highly stable and enable one to derive highly accurate analytical approximations of Hubble's rate in terms of the cosmographic series. Finally, we check our theoretical predictions by setting bounds on cosmographic parameters through Monte Carlo integration techniques, based on the Metropolis-Hastings algorithm. We apply our technique to high-redshift cosmic data, using the Joint Light-curve Analysis supernovae sample and the most recent versions of Hubble parameter and baryon acoustic oscillation measurements. We find that cosmography with Taylor series fails to be predictive with the aforementioned data sets, while turns out to be much more stable using the Chebyshev approach.

Where do moral decisions come from?

PubMed

Crigger, Bette-Jane

1996-01-01

[Mark] Johnson asks us to take seriously theory as an imaginative construction that offers, not an objective account of the world, but a dynamic, intersubjective construal of it....A common feature [of the four books discussed] is the conviction that moral universals are somehow bound up with dynamic processes that have their origin in the human form, not with disembodied rules or rational arguments per se.

Modeling of the financial market using the two-dimensional anisotropic Ising model

NASA Astrophysics Data System (ADS)

Lima, L. S.

2017-09-01

We have used the two-dimensional classical anisotropic Ising model in an external field and with an ion single anisotropy term as a mathematical model for the price dynamics of the financial market. The model presented allows us to test within the same framework the comparative explanatory power of rational agents versus irrational agents with respect to the facts of financial markets. We have obtained the mean price in terms of the strong of the site anisotropy term Δ which reinforces the sensitivity of the agent's sentiment to external news.

Neutron diffraction of acetazolamide-bound human carbonic anhydrase II reveals atomic details of drug binding

PubMed Central

Fisher, S. Zoë; Aggarwal, Mayank; Kovalevsky, Andrey Y.; Silverman, David N.; McKenna, Robert

2012-01-01

Carbonic anhydrases (CAs) catalyze the hydration of CO2 forming HCO3− and a proton, an important reaction for many physiological processes including respiration, fluid secretion, and pH regulation. As such, CA isoforms are prominent clinical targets for treating various diseases. The clinically used acetazolamide (AZM) is a sulfonamide that binds with high affinity to human CA isoform II (HCA II). There are several X-ray structures available of AZM bound to various CA isoforms, but these complexes do not show the charged state of AZM, or hydrogen (H) atom positions of the protein and solvent. Neutron diffraction is a useful technique for directly observing H atoms and the mapping of H-bonding networks that can greatly contribute to rational drug design. To this end the neutron structure of H/D exchanged HCA II crystals in complex with AZM was determined. The structure reveals the molecular details of AZM binding and the charged state of the bound drug. This represents the first determined neutron structure of a clinically used drug bound to its target. PMID:22928733

N-cyanoimidazole and diimidazole imine: water-soluble condensing agents for the formation of the phosphodiester bond

NASA Technical Reports Server (NTRS)

Ferris, J. P.; Huang, C. H.; Hagan, W. J. Jr

1989-01-01

The reaction of BrCN with imidazole results in the formation of N-cyanoimidazole and diimidazole imine. These compounds were shown to be useful condensing agents for the formation of the phosphodiester bound in aqueous solution.

A rational eating model of binges, diets and obesity.

PubMed

Dragone, Davide

2009-07-01

This paper addresses the rapid diffusion of obesity and the existence of different individual patterns of food consumption between non-dieters and chronic dieters. I propose a rational eating model where a forward-looking agent optimizes the intertemporal satisfaction from eating, taking into account the cost of changing consumption habits and the negative health consequences of having a non-optimal body weight. Consistent with the evidence, I show that the intertemporal maximization problem leads to a condition of overweightness, and that heterogeneity in the individual relevance of habits in consumption can determine the observed differences in the individual intertemporal patterns of food consumption and body weight. Sufficient conditions for determining when the convergence to the steady state implies oscillations or is monotonic are given. In the former case, the agent optimally alternates diets and binges until the steady state is reached, in the latter a regular intertemporal pattern of food consumption is optimal.

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.

Overcoming resistance to molecularly targeted anticancer therapies: Rational drug combinations based on EGFR and MAPK inhibition for solid tumours and haematologic malignancies.

PubMed

Tortora, Giampaolo; Bianco, Roberto; Daniele, Gennaro; Ciardiello, Fortunato; McCubrey, James A; Ricciardi, Maria Rosaria; Ciuffreda, Ludovica; Cognetti, Francesco; Tafuri, Agostino; Milella, Michele

2007-06-01

Accumulating evidence suggests that cancer can be envisioned as a "signaling disease", in which alterations in the cellular genome affect the expression and/or function of oncogenes and tumour suppressor genes. This ultimately disrupts the physiologic transmission of biochemical signals that normally regulate cell growth, differentiation and programmed cell death (apoptosis). From a clinical standpoint, signal transduction inhibition as a therapeutic strategy for human malignancies has recently achieved remarkable success. However, as additional drugs move forward into the clinical arena, intrinsic and acquired resistance to "targeted" agents becomes an issue for their clinical utility. One way to overcome resistance to targeted agents is to identify genetic and epigenetic aberrations underlying sensitivity/resistance, thus enabling the selection of patients that will most likely benefit from a specific therapy. Since resistance often ensues as a result of the concomitant activation of multiple, often overlapping, signaling pathways, another possibility is to interfere with multiple, cross-talking pathways involved in growth and survival control in a rational, mechanism-based, fashion. These concepts may be usefully applied, among others, to agents that target two major signal transduction pathways: the one initiated by epidermal growth factor receptor (EGFR) signaling and the one converging on mitogen-activated protein kinase (MAPK) activation. Here, we review the molecular mechanisms of sensitivity/resistance to EGFR inhibitors, as well as the rationale for combining them with other targeted agents, in an attempt to overcome resistance. In the second part of the paper, we review MAPK-targeted agents, focusing on their therapeutic potential in haematologic malignancies, and examine the prospects for combinations of MAPK inhibitors with cytotoxic agents or other signal transduction-targeted agents to obtain synergistic anti-tumour effects.

Overcoming resistance to molecularly targeted anticancer therapies: rational drug combinations based on EGFR and MAPK inhibition for solid tumours and haematologic malignancies

PubMed Central

Tortora, Giampaolo; Bianco, Roberto; Daniele, Gennaro; Ciardiello, Fortunato; McCubrey, James A; Ricciardi, Maria Rosaria; Ciuffreda, Ludovica; Cognetti, Francesco; Tafuri, Agostino; Milella, Michele

2007-01-01

Accumulating evidence suggests that cancer can be envisioned as a “signaling disease”, in which alterations in the cellular genome affect the expression and/or function of oncogenes and tumour suppressor genes. This ultimately disrupts the physiologic transmission of biochemical signals that normally regulate cell growth, differentiation and programmed cell death (apoptosis). From a clinical standpoint, signal transduction inhibition as a therapeutic strategy for human malignancies has recently achieved remarkable success. However, as additional drugs move forward into the clinical arena, intrinsic and acquired resistance to “targeted” agents becomes an issue for their clinical utility. One way to overcome resistance to targeted agents is to identify genetic and epigenetic aberrations underlying sensitivity/resistance, thus enabling the selection of patients that will most likely benefit from a specific therapy. Since resistance often ensues as a result of the concomitant activation of multiple, often overlapping, signaling pathways, another possibility is to interfere with multiple, cross-talking pathways involved in growth and survival control in a rational, mechanism-based, fashion. These concepts may be usefully applied, among others, to agents that target two major signal transduction pathways: the one initiated by epidermal growth factor receptor (EGFR) signaling and the one converging on mitogen-activated protein kinase (MAPK) activation. Here we review the molecular mechanisms of sensitivity/resistance to EGFR inhibitors, as well as the rationale for combining them with other targeted agents, in an attempt to overcome resistance. In the second part of the paper, we review MAPK-targeted agents, focusing on their therapeutic potential in hematologic malignancies, and examine the prospects for combinations of MAPK inhibitors with cytotoxic agents or other signal transduction-targeted agents to obtain synergistic anti-tumour effects. PMID:17482503

Evasion in the plane

NASA Technical Reports Server (NTRS)

Leitmann, G.; Liu, H. S.

1977-01-01

Dynamic systems were considered subject to control by two agents, one of whom desires that no trajectory of the system emanating from outside a given set, intersects that set no matter what the admissible actions of the other agent. Constructive conditions sufficient to yield a feedback control for the agent seeking avoidance were employed to deduce an evader control for the planar pursuit-evasion problem with bounded normal accelerations.

Bound Rationality and Organizational Learning.

DTIC Science & Technology

1989-09-23

psychology of people living In an organizational environment. The complaint was usually registered by sociologists, and was not without merit. We need...species of what Bill Starbuck has called "knowledge intensive organizations." Let us take the case of a university that wants to innovate along some...control gear would be an example, a considerable fraction of Ideas for new products originates with a knowledge or customers ’ needs and problems - the

Adaptability: Time to Start Thinking about Thinking

DTIC Science & Technology

2015-05-21

larger whole.66 An example of a paradox is one cannot be happy if one is sad, but these two emotions are really part of an overall state of being...which triggers bodily responses; those bodily responses have implications on cognitive processes like working memory, flexibility, and creativity...Kahneman, Thinking, Fast and Slow (New York: Farrar, Straus and Giroux, 2011), 3. 99 Daniel Kahneman, “ Maps of Bounded Rationality: Psychology for

The structure of a market containing boundedly rational firms

NASA Astrophysics Data System (ADS)

Ibrahim, Adyda; Zura, Nerda; Saaban, Azizan

2017-11-01

The structure of a market is determined by the number of active firms in it. Over time, this number is affected by the exit of existing firms, called incumbents, and entries of new firms, called entrant. In this paper, we considered a market governed by the Cobb-Douglas utility function such that the demand function is isoelastic. Each firm is assumed to produce a single homogenous product under a constant unit cost. Furthermore, firms are assumed to be boundedly rational in adjusting their outputs at each period. A firm is considered to exit the market if its output is negative. In this paper, the market is assumed to have zero barrier-to-entry. Therefore, the exiting firm can reenter the market if its output is positive again, and new firms can enter the market easily. Based on these assumptions and rules, a mathematical model was developed and numerical simulations were run using Matlab. By setting certain values for the parameters in the model, initial numerical simulations showed that in the long run, the number of firms that manages to survive the market varies between zero to 30. This initial result is consistent with the idea that a zero barrier-to-entry may produce a perfectly competitive market.

Design and application of a CA-BDI model to determine farmers' land-use behavior.

PubMed

Liang, Xiaoying; Chen, Hai; Wang, Yanni; Song, Shixiong

2016-01-01

The belief-desire-intention (BDI) model has been widely used to construct reasoning systems for complex tasks in dynamic environments. We have designed a capabilities and abilities (CA)-BDI farmer decision-making model, which is an extension of the BDI architecture and includes internal representations for farmer household Capabilities and Abilities. This model is used to explore farmer learning mechanisms and to simulate the bounded rational decisions made by farmer households. Our case study focuses on the Gaoqu Commune of Mizhi County, Shaanxi Province, China, where scallion is one of the main cash crops. After comparing the differences between actual land-use changes from 2007 to 2009 and the simulation results, we analyze the validity of the model and discuss the potential and limitations of the farmer land-use decision-making model under three scenarios. Based on the design and implementation of the model, the following conclusions can be drawn: (1) the CA-BDI framework is an appropriate model for exploring learning mechanisms and simulating bounded rational decisions; and (2) local governments should encourage scallion planting by assisting scallion farmer cooperatives and farmers to understand the market risk, standardize the rules of their cooperation, and supervise the contracts made between scallion cooperatives and farmers.

Approximating the 0-1 Multiple Knapsack Problem with Agent Decomposition and Market Negotiation

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

Smolinski, B.

The 0-1 multiple knapsack problem appears in many domains from financial portfolio management to cargo ship stowing. Methods for solving it range from approximate algorithms, such as greedy algorithms, to exact algorithms, such as branch and bound. Approximate algorithms have no bounds on how poorly they perform and exact algorithms can suffer from exponential time and space complexities with large data sets. This paper introduces a market model based on agent decomposition and market auctions for approximating the 0-1 multiple knapsack problem, and an algorithm that implements the model (M(x)). M(x) traverses the solution space rather than getting caught inmore » a local maximum, overcoming an inherent problem of many greedy algorithms. The use of agents ensures that infeasible solutions are not considered while traversing the solution space and that traversal of the solution space is not just random, but is also directed. M(x) is compared to a bound and bound algorithm (BB) and a simple greedy algorithm with a random shuffle (G(x)). The results suggest that M(x) is a good algorithm for approximating the 0-1 Multiple Knapsack problem. M(x) almost always found solutions that were close to optimal in a fraction of the time it took BB to run and with much less memory on large test data sets. M(x) usually performed better than G(x) on hard problems with correlated data.« less

Identification and calculation of the universal asymptote for drag reduction by polymers in wall bounded turbulence.

PubMed

Benzi, Roberto; De Angelis, Elisabetta; L'vov, Victor S; Procaccia, Itamar

2005-11-04

Drag reduction by polymers in wall turbulence is bounded from above by a universal maximal drag reduction (MDR) velocity profile that is a log law, estimated experimentally by Virk as V+(y+) approximately 11.7logy+ - 17. Here V+(y+) and y+ are the mean streamwise velocity and the distance from the wall in "wall" units. In this Letter we propose that this MDR profile is an edge solution of the Navier-Stokes equations (with an effective viscosity profile) beyond which no turbulent solutions exist. This insight rationalizes the universality of the MDR and provides a maximum principle which allows an ab initio calculation of the parameters in this law without any viscoelastic experimental input.

Flocking with connectivity preservation for disturbed nonlinear multi-agent systems by output feedback

NASA Astrophysics Data System (ADS)

Li, Ping; Zhang, Baoyong; Ma, Qian; Xu, Shengyuan; Chen, Weimin; Zhang, Zhengqiang

2018-05-01

This paper considers the problem of flocking with connectivity preservation for a class of disturbed nonlinear multi-agent systems. In order to deal with the nonlinearities in the dynamic of all agents, some auxiliary variables are introduced into the state observer for stability analysis. By proposing a bounded potential function and using adaptive theory, a novel output feedback consensus algorithm is developed to guarantee that the states of all agents achieve flocking with connectivity preservation.

Aggregate age-at-marriage patterns from individual mate-search heuristics.

PubMed

Todd, Peter M; Billari, Francesco C; Simão, Jorge

2005-08-01

The distribution of age at first marriage shows well-known strong regularities across many countries and recent historical periods. We accounted for these patterns by developing agent-based models that simulate the aggregate behavior of individuals who are searching for marriage partners. Past models assumed fully rational agents with complete knowledge of the marriage market; our simulated agents used psychologically plausible simple heuristic mate search rules that adjust aspiration levels on the basis of a sequence of encounters with potential partners. Substantial individual variation must be included in the models to account for the demographically observed age-at-marriage patterns.

Incorporating BDI Agents into Human-Agent Decision Making Research

NASA Astrophysics Data System (ADS)

Kamphorst, Bart; van Wissen, Arlette; Dignum, Virginia

Artificial agents, people, institutes and societies all have the ability to make decisions. Decision making as a research area therefore involves a broad spectrum of sciences, ranging from Artificial Intelligence to economics to psychology. The Colored Trails (CT) framework is designed to aid researchers in all fields in examining decision making processes. It is developed both to study interaction between multiple actors (humans or software agents) in a dynamic environment, and to study and model the decision making of these actors. However, agents in the current implementation of CT lack the explanatory power to help understand the reasoning processes involved in decision making. The BDI paradigm that has been proposed in the agent research area to describe rational agents, enables the specification of agents that reason in abstract concepts such as beliefs, goals, plans and events. In this paper, we present CTAPL: an extension to CT that allows BDI software agents that are written in the practical agent programming language 2APL to reason about and interact with a CT environment.

Cottonseed meal, dehydrated grass and ascorbic acid as dietary factors preventing toxicity of vanadium for the chick

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

Berg, L.R.; Lawrence, W.W.

1971-01-01

Studies have been conducted which show that the replacement of 5% sucrose in a sucrose-fish meal diet for chicks with degossypolized cottonseed meal prevents the toxicity of 20 ppm added vanadium. The addition of 5% dehydrated grass to the same ration markedly reduced the toxicity symptoms. No such reduction in vanadium toxicity resulted when soybean meal, corn gluten meal, meat meal, fish meal, casein, isolated soybean protein, zein or wheat gluten were added to the ration. No evidence was found that the gossypol remaining in the cottonseed meal was the detoxifying agent. The addition of 0.25 to 0.50% ascorbic acidmore » to the sucrose-fish meal basal ration prevented the toxic symptoms resulting from the addition of 20 ppm vanadium derived from HN/sub 4/VO/sub 3/. The vanadium derived from VOSO/sub 4/ and VOCl/sub 2/ (vanadium valence 4) was as toxic as vanadium derived from HN/sub 4/VO/sub 3/ (V = valence 5). This leads one to question that the action of ascorbic acid in reducing vanadium toxicity is through its property of a reducing agent which might change the vanadium in VH/sub 4/VO/sub 3/ to a lower valence, presumably less toxic.« less

From Wald to Savage: homo economicus becomes a Bayesian statistician.

PubMed

Giocoli, Nicola

2013-01-01

Bayesian rationality is the paradigm of rational behavior in neoclassical economics. An economic agent is deemed rational when she maximizes her subjective expected utility and consistently revises her beliefs according to Bayes's rule. The paper raises the question of how, when and why this characterization of rationality came to be endorsed by mainstream economists. Though no definitive answer is provided, it is argued that the question is of great historiographic importance. The story begins with Abraham Wald's behaviorist approach to statistics and culminates with Leonard J. Savage's elaboration of subjective expected utility theory in his 1954 classic The Foundations of Statistics. The latter's acknowledged fiasco to achieve a reinterpretation of traditional inference techniques along subjectivist and behaviorist lines raises the puzzle of how a failed project in statistics could turn into such a big success in economics. Possible answers call into play the emphasis on consistency requirements in neoclassical theory and the impact of the postwar transformation of U.S. business schools. © 2012 Wiley Periodicals, Inc.

Undecidability in macroeconomics

NASA Technical Reports Server (NTRS)

Chandra, Siddharth; Chandra, Tushar Deepak

1993-01-01

In this paper we study the difficulty of solving problems in economics. For this purpose, we adopt the notion of undecidability from recursion theory. We show that certain problems in economics are undecidable, i.e., cannot be solved by a Turing Machine, a device that is at least as powerful as any computational device that can be constructed. In particular, we prove that even in finite closed economies subject to a variable initial condition, in which a social planner knows the behavior of every agent in the economy, certain important social planning problems are undecidable. Thus, it may be impossible to make effective policy decisions. Philosophically, this result formally brings into question the Rational Expectations Hypothesis which assumes that each agent is able to determine what it should do if it wishes to maximize its utility. We show that even when an optimal rational forecast exists for each agency (based on the information currently available to it), agents may lack the ability to make these forecasts. For example, Lucas describes economic models as 'mechanical, artificial world(s), populated by ... interacting robots'. Since any mechanical robot can be at most as computationally powerful as a Turing Machine, such economies are vulnerable to the phenomenon of undecidability.

Rational Degenerations of M-Curves, Totally Positive Grassmannians and KP2-Solitons

NASA Astrophysics Data System (ADS)

Abenda, Simonetta; Grinevich, Petr G.

2018-03-01

We establish a new connection between the theory of totally positive Grassmannians and the theory of M-curves using the finite-gap theory for solitons of the KP equation. Here and in the following KP equation denotes the Kadomtsev-Petviashvili 2 equation [see (1)], which is the first flow from the KP hierarchy. We also assume that all KP times are real. We associate to any point of the real totally positive Grassmannian Gr^{tp} (N,M) a reducible curve which is a rational degeneration of an M-curve of minimal genus {g=N(M-N)} , and we reconstruct the real algebraic-geometric data á la Krichever for the underlying real bounded multiline KP soliton solutions. From this construction, it follows that these multiline solitons can be explicitly obtained by degenerating regular real finite-gap solutions corresponding to smooth M-curves. In our approach, we rule the addition of each new rational component to the spectral curve via an elementary Darboux transformation which corresponds to a section of a specific projection Gr^{tp} (r+1,M-N+r+1)\\mapsto Gr^{tp} (r,M-N+r).

RNA synthetic mechanisms employed by diverse families of RNA viruses.

PubMed

McDonald, Sarah M

2013-01-01

RNA viruses are ubiquitous in nature, infecting every known organism on the planet. These viruses can also be notorious human pathogens with significant medical and economic burdens. Central to the lifecycle of an RNA virus is the synthesis of new RNA molecules, a process that is mediated by specialized virally encoded enzymes called RNA-dependent RNA polymerases (RdRps). RdRps directly catalyze phosphodiester bond formation between nucleoside triphosphates in an RNA-templated manner. These enzymes are strikingly conserved in their structural and functional features, even among diverse RNA viruses belonging to different families. During host cell infection, the activities of viral RdRps are often regulated by viral cofactor proteins. Cofactors can modulate the type and timing of RNA synthesis by directly engaging the RdRp and/or by indirectly affecting its capacity to recognize template RNA. High-resolution structures of RdRps as apoenzymes, bound to RNA templates, in the midst of catalysis, and/or interacting with regulatory cofactor proteins, have dramatically increased our understanding of viral RNA synthetic mechanisms. Combined with elegant biochemical studies, such structures are providing a scientific platform for the rational design of antiviral agents aimed at preventing and treating RNA virus-induced diseases. Copyright © 2013 John Wiley & Sons, Ltd.

Co-Binding of Pharmaceutical Compounds at Mineral Surfaces: Molecular Investigations of Dimer Formation at Goethite/Water Interfaces.

PubMed

Xu, Jing; Marsac, Rémi; Costa, Dominique; Cheng, Wei; Wu, Feng; Boily, Jean-François; Hanna, Khalil

2017-08-01

The emergence of antibiotic and anti-inflammatory agents in aquatic and terrestrial systems is becoming a serious threat to human and animal health worldwide. Because pharmaceutical compounds rarely exist individually in nature, interactions between various compounds can have unforeseen effects on their binding to mineral surfaces. This work demonstrates this important possibility for the case of two typical antibiotic and anti-inflammatory agents (nalidixic acid (NA) and niflumic acid (NFA)) bound at goethite (α-FeOOH) used as a model mineral surface. Our multidisciplinary study, which makes use of batch sorption experiments, vibration spectroscopy and periodic density functional theory calculations, reveals enhanced binding of the otherwise weakly bound NFA caused by unforeseen intermolecular interactions with mineral-bound NA. This enhancement is ascribed to the formation of a NFA-NA dimer whose energetically favored formation (-0.5 eV compared to free molecules) is predominantly driven by van der Waals interactions. A parallel set of efforts also showed that no cobinding occurred with sulfamethoxazole (SMX) because of the lack of molecular interactions with coexisting contaminants. As such, this article raises the importance of recognizing drug cobinding, and lack of cobinding, for predicting and developing policies on the fate of complex mixtures of antibiotics and anti-inflammatory agents in nature.

[Antiseptics and disinfectants: aiming at rational use. Recommendations of the Advisory Committee on Healthcare Associated Infections. Sociedad Chilena de Infectología].

PubMed

Diomedi, Alexis; Chacón, Eiiana; Delpiano, Luis; Hervé, Beatrice; Jemenao, M Irene; Medel, Myriam; Quintanilla, Marcela; Riedel, Gisela; Tinoco, Javier; Cifuentes, Marcela

2017-04-01

Proper use of antiseptics and disinfectants, is an essential tool to prevent the spread of infectious agents and to control of healthcare-associated infections (HAI). Given the increasing importance of environmental aspects, as well as several advances and updates in the field of its proper use at local and intemational level, the SOCHINF HAI Advisory Committee considers that it is necessary to develop a guide for the rational use of antiseptics and disinfectants, which it will provide consistent scientific basis with that purpose.

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.

Mill and the right to remain uninformed.

PubMed

Strasser, M

1986-08-01

In a recent article in the Journal of Medicine and Philosophy, David Ost (1984) claims that patients do not have a right to waive their right to information. He argues that patients cannot make informed rational decisions without full information and thus, a right to waive information would involve a right to avoid one's responsibility to act as an autonomous moral agent. In support of his position, Ost cites a passage from Mill. Yet, a correct interpretation of the passage in question would support one's right to remain uninformed in certain situations. If the information would hurt one's chances for survival or hurt one's ability to make calm, rational decisions, then one not only does not have a duty to find out the information, but one's exercising one's right to remain uninformed may be the only rational course of action to take.

Laws of cognition and the cognition of law.

PubMed

Kahan, Dan M

2015-02-01

This paper presents a compact synthesis of the study of cognition in legal decisionmaking. Featured dynamics include the story-telling model (Pennington & Hastie, 1986), lay prototypes (Smith, 1991), motivated cognition (Sood, 2012), and coherence-based reasoning (Simon, Pham, Le, & Holyoak, 2001). Unlike biases and heuristics understood to bound or constrain rationality, these dynamics identify how information shapes a variety of cognitive inputs-from prior beliefs to perceptions of events to the probative weight assigned new information-that rational decisionmaking presupposes. The operation of these mechanisms can be shown to radically alter the significance that jurors give to evidence, and hence the conclusions they reach, within a Bayesian framework of information processing. How these dynamics interact with the professional judgment of lawyers and judges, the paper notes, remains in need of investigation. Copyright © 2014 Elsevier B.V. All rights reserved.

PAYING FOR PERFORMANCE: THE POWER OF INCENTIVES OVER HABITS

PubMed Central

Sindelar, Jody L.

2010-01-01

New evidence suggests that individuals do not always make rational decisions, especially with regard to health habits. Smoking, misuse of alcohol, overeating and illicit drug use are leading causes of morbidity and mortality. Thus, influencing health habits is critical for improving overall health and well-being. This editorial argues that economists should take a more active role in shaping individuals’ health habits. Two recent innovations in economic theory pave the way. One change is that some economists now view rationality as bounded and willpower in short supply. Another, related to the first, is a more accepting perspective on paternalism, authorizing economists to help individuals make better choices when the neoclassical model breaks down. Findings from psychology offer incentive-based approaches; specifically, contingency management (CM). Economists could use this approach as a basis for developing public and private policies. PMID:18348117

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

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

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

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

Heterocyclic periphery in the design of carbonic anhydrase inhibitors: 1,2,4-Oxadiazol-5-yl benzenesulfonamides as potent and selective inhibitors of cytosolic hCA II and membrane-bound hCA IX isoforms.

PubMed

Krasavin, Mikhail; Shetnev, Anton; Sharonova, Tatyana; Baykov, Sergey; Tuccinardi, Tiziano; Kalinin, Stanislav; Angeli, Andrea; Supuran, Claudiu T

2018-02-01

A series of novel aromatic primary sulfonamides decorated with diversely substituted 1,2,4-oxadiazole periphery groups has been prepared using a parallel chemistry approach. The compounds displayed a potent inhibition of cytosolic hCA II and membrane-bound hCA IX isoforms. Due to a different cellular localization of the two target enzymes, the compounds can be viewed as selective inhibition tools for either isoform, depending on the cellular permeability profile. The SAR findings revealed in this study has been well rationalized by docking simulation of the key compounds against the crystal structures of the relevant hCA isoforms. Copyright © 2017. Published by Elsevier Inc.

Quantum Speedup for Active Learning Agents

NASA Astrophysics Data System (ADS)

Paparo, Giuseppe Davide; Dunjko, Vedran; Makmal, Adi; Martin-Delgado, Miguel Angel; Briegel, Hans J.

2014-07-01

Can quantum mechanics help us build intelligent learning agents? A defining signature of intelligent behavior is the capacity to learn from experience. However, a major bottleneck for agents to learn in real-life situations is the size and complexity of the corresponding task environment. Even in a moderately realistic environment, it may simply take too long to rationally respond to a given situation. If the environment is impatient, allowing only a certain time for a response, an agent may then be unable to cope with the situation and to learn at all. Here, we show that quantum physics can help and provide a quadratic speedup for active learning as a genuine problem of artificial intelligence. This result will be particularly relevant for applications involving complex task environments.

A Markov Chain Approach to Probabilistic Swarm Guidance

NASA Technical Reports Server (NTRS)

Acikmese, Behcet; Bayard, David S.

2012-01-01

This paper introduces a probabilistic guidance approach for the coordination of swarms of autonomous agents. The main idea is to drive the swarm to a prescribed density distribution in a prescribed region of the configuration space. In its simplest form, the probabilistic approach is completely decentralized and does not require communication or collabo- ration between agents. Agents make statistically independent probabilistic decisions based solely on their own state, that ultimately guides the swarm to the desired density distribution in the configuration space. In addition to being completely decentralized, the probabilistic guidance approach has a novel autonomous self-repair property: Once the desired swarm density distribution is attained, the agents automatically repair any damage to the distribution without collaborating and without any knowledge about the damage.

Wealth distribution, Pareto law, and stretched exponential decay of money: Computer simulations analysis of agent-based models

NASA Astrophysics Data System (ADS)

Aydiner, Ekrem; Cherstvy, Andrey G.; Metzler, Ralf

2018-01-01

We study by Monte Carlo simulations a kinetic exchange trading model for both fixed and distributed saving propensities of the agents and rationalize the person and wealth distributions. We show that the newly introduced wealth distribution - that may be more amenable in certain situations - features a different power-law exponent, particularly for distributed saving propensities of the agents. For open agent-based systems, we analyze the person and wealth distributions and find that the presence of trap agents alters their amplitude, leaving however the scaling exponents nearly unaffected. For an open system, we show that the total wealth - for different trap agent densities and saving propensities of the agents - decreases in time according to the classical Kohlrausch-Williams-Watts stretched exponential law. Interestingly, this decay does not depend on the trap agent density, but rather on saving propensities. The system relaxation for fixed and distributed saving schemes are found to be different.

Environmental Agency in Read-Alouds

ERIC Educational Resources Information Center

Oliveira, Alandeom W.; Rogers, Patterson; Quigley, Cassie F.; Samburskiy, Denis; Barss, Kimberly; Rivera, Seema

2015-01-01

Despite growing interest in helping students become agents of environmental change who can, through informed decision-making and action-taking, transform environmentally detrimental forms of human activity, science educators have reduced agency to rationality by overlooking sociocultural influences such as norms and values. We tackle this issue by…

Focusing on relationships, not information, respects autonomy during antenatal consultations.

PubMed

Gaucher, Nathalie; Payot, Antoine

2017-01-01

Policy statements regarding antenatal consultations for preterm labour are guided by physicians' concerns for upholding the legal doctrine of informed consent, through the provision of standardised homogeneous medical information. This approach, led by classical in-control conceptions of patient autonomy, conceives moral agents as rational, independent, self-sufficient decision-makers. Recent studies on these antenatal consultations have explored patients' perspectives, and these differ from guidelines' suggestions. Relational autonomy - which understands moral agents as rational, emotional, creative and interdependent - resonates impressively with these new data. A model for antenatal consultations is proposed. This approach encourages clinicians to explore individual patients' lived experiences and engage in trusting empowering relationships. Moreover, it calls on physicians to enhance patients' relational autonomy by becoming advocates for their patients within healthcare institutions and professional organisations, while calling for broadscale policy changes to encourage further funding and support in investigations of the patient's voice. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

What does the Sr-substituted 2.1 Å resolution crystal structure of photosystem II reveal about the water oxidation mechanism?

PubMed

Terrett, Richard; Petrie, Simon; Pace, Ron J; Stranger, Robert

2014-03-25

A density functional study of the Sr-substituted photosystem II water oxidising complex demonstrates that its recent X-ray crystal structure is consistent with a (Mn(III))4 oxidation state pattern, and with a Sr-bound hydroxide ion. The Sr-water-hydroxide interactions rationalize differences in the exchange rates of substrate water and kinetics of dioxygen bond formation relative to the Ca-containing structure.

Rational design of orally-active, pyrrolidine-based progesterone receptor partial agonists

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

Thompson, Scott K.; Washburn, David G.; Frazee, James S.

2010-09-03

Using the X-ray crystal structure of an amide-based progesterone receptor (PR) partial agonist bound to the PR ligand binding domain, a novel PR partial agonist class containing a pyrrolidine ring was designed. Members of this class of N-alkylpyrrolidines demonstrate potent and highly selective partial agonism of the progesterone receptor, and one of these analogs was shown to be efficacious upon oral dosing in the OVX rat model of estrogen opposition.

Controllable reductive method for synthesizing metal-containing particles

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

Moon, Ji-Won; Jung, Hyunsung; Phelps, Tommy Joe

The invention is directed to a method for producing metal-containing particles, the method comprising subjecting an aqueous solution comprising a metal salt, E.sub.h, lowering reducing agent, pH adjusting agent, and water to conditions that maintain the E.sub.h value of the solution within the bounds of an E.sub.h-pH stability field corresponding to the composition of the metal-containing particles to be produced, and producing said metal-containing particles in said aqueous solution at a selected E.sub.h value within the bounds of said E.sub.h-pH stability field. The invention is also directed to the resulting metal-containing particles as well as devices in which they aremore » incorporated.« less

The impact of loss sensitivity on a mobile phone supply chain system stability based on the chaos theory

NASA Astrophysics Data System (ADS)

Ma, Junhai; Xie, Lei

2018-02-01

This paper, based on the China's communications and the current situation of the mobile phone industry, focuses on the stability of a supply chain system that consists of one supplier and one bounded rational retailer. We explore the influence of the decision makers' loss sensitivity and decision adjustment speed on the stability of the supply chain. It is found that when the retailer is not sensitive to the loss or adjusts decisions cautiously, the system can be stable. The single-retailer model is extended to a multi-retailer one to study the influence of competition on the system stability. The results show that the market share of each retailer does not affect the system stability when it is fixed. The decision of each retailer does not affect that of any other retailer and the system stability. We present two decision adjustment rules (;bounded rationality expectation (BRE); and "adaptive exponential smoothing (AES)") and compare their performances on the system stability, and find that the AES rule does not affect the system stability, while the BRE rule will make the system stability be sensitive to the retailers' loss sensitivity and the decision adjustment speed. We also reveal the unstable system's negative impact on the retailers' decisions and profits, to emphasize the importance to maintain the system stability.

On one-dimensional compressible Navier-Stokes equations for a reacting mixture in unbounded domains

NASA Astrophysics Data System (ADS)

Li, Siran

2017-10-01

In this paper we consider the one-dimensional Navier-Stokes system for a heat-conducting, compressible reacting mixture which describes the dynamic combustion of fluids of mixed kinds on unbounded domains. This model has been discussed on bounded domains by Chen (SIAM J Math Anal 23:609-634, 1992) and Chen-Hoff-Trivisa (Arch Ration Mech Anal 166:321-358, 2003), among others, in which the reaction rate function is a discontinuous function obeying the Arrhenius' law of thermodynamics. We prove the global existence of weak solutions to this model on one-dimensional unbounded domains with large initial data in H^1. Moreover, the large-time behaviour of the weak solution is identified. In particular, the uniform-in-time bounds for the temperature and specific volume have been established via energy estimates. For this purpose we utilise techniques developed by Kazhikhov-Shelukhin (cf. Kazhikhov in Siber Math J 23:44-49, 1982; Solonnikov and Kazhikhov in Annu Rev Fluid Mech 13:79-95, 1981) and refined by Jiang (Commun Math Phys 200:181-193, 1999, Proc R Soc Edinb Sect A 132:627-638, 2002), as well as a crucial estimate in the recent work by Li-Liang (Arch Ration Mech Anal 220:1195-1208, 2016). Several new estimates are also established, in order to treat the unbounded domain and the reacting terms.

Influences of Agents with a Self-Reputation Awareness Component in an Evolutionary Spatial IPD Game

PubMed Central

Huang, Chung-Yuan; Lee, Chun-Liang

2014-01-01

Iterated prisoner’s dilemma (IPD) researchers have shown that strong positive reputations plus an efficient reputation evaluation system encourages both sides to pursue long-term collaboration and to avoid falling into mutual defection cycles. In agent-based environments with reliable reputation rating systems, agents interested in maximizing their private interests must show concern for other agents as well as their own self-reputations–an important capability that standard IPD game agents lack. Here we present a novel learning agent model possessing self-reputation awareness. Agents in our proposed model are capable of evaluating self-behaviors based on a mix of public and private interest considerations, and of testing various solutions aimed at meeting social standards. Simulation results indicate multiple outcomes from the addition of a small percentage of self-reputation awareness agents: faster cooperation, faster movement toward stability in an agent society, a higher level of public interest in the agent society, the resolution of common conflicts between public and private interests, and a lower potential for rational individual behavior to transform into irrational group behavior. PMID:24945966

Environmental agency in read-alouds

NASA Astrophysics Data System (ADS)

Oliveira, Alandeom W.; Rogers, Patterson; Quigley, Cassie F.; Samburskiy, Denis; Barss, Kimberly; Rivera, Seema

2015-06-01

Despite growing interest in helping students become agents of environmental change who can, through informed decision-making and action-taking, transform environmentally detrimental forms of human activity, science educators have reduced agency to rationality by overlooking sociocultural influences such as norms and values. We tackle this issue by examining how elementary teachers and students negotiate and attribute responsibility, credit, or blame for environmental events during three environmental read-alouds. Our verbal analysis and visual representation of meta-agentive discourse revealed varied patterns of agential attribution. First, humans were simultaneously attributed negative agentive roles (agents of endangerment and imbalance) and positive agentive roles (agents of prevention, mitigation, and balance). Second, while wolves at Yellowstone were constructed as intentional (human-like) agents when they crossed over into the human world to kill livestock in nearby farms, polar bears in the Arctic were denied any form of agential responsibility when they approached people's homes. Third, anthropogenic causation of global warming was constructed as distal and indirect chains of cause and effect (i.e., sophisticated sequences of ripple effects), whereas its mitigation and prevention assumed the form of simple and unidirectional causative links (direct and proximal causality). Fourth, the notion of balance of nature was repeatedly used as a justification for environmental conservation but its cause and dynamic nature remained unclear. And, fifth, while one teacher promoted environmental agency by encouraging students to experience positive emotions such as love of nature, freedom, and oneness with nature, the other teachers encouraged students to experience negative emotions such as self-blame and guilt. This study's main significance is that it highlights the need for environmental educators who set out to promote environmental agency to expand the focus of their instructional efforts beyond rational argumentation and reasoning. It also underscores the importance of increasing school teachers' awareness of implicit discursive messages in particular patterns of environmental agency attribution when discussing environmental issues with students and implementing pedagogical strategies centered on oral deliberation such as read-alouds.

Developmental Liberalism

ERIC Educational Resources Information Center

Curren, Randall

2006-01-01

In this essay, Randall Curren identifies a type of liberalism that incorporates empirical claims about the development of agency and rationality, and responds to the criticism that liberalism rests on an incoherent conception of "autonomous agency." He argues that moral agents did indeed "become ghosts" somewhere en route from Aristotle to Kant,…

Distributed adaptive neural network control for a class of heterogeneous nonlinear multi-agent systems subject to actuation failures

NASA Astrophysics Data System (ADS)

Cui, Bing; Zhao, Chunhui; Ma, Tiedong; Feng, Chi

2017-02-01

In this paper, the cooperative adaptive consensus tracking problem for heterogeneous nonlinear multi-agent systems on directed graph is addressed. Each follower is modelled as a general nonlinear system with the unknown and nonidentical nonlinear dynamics, disturbances and actuator failures. Cooperative fault tolerant neural network tracking controllers with online adaptive learning features are proposed to guarantee that all agents synchronise to the trajectory of one leader with bounded adjustable synchronisation errors. With the help of linear quadratic regulator-based optimal design, a graph-dependent Lyapunov proof provides error bounds that depend on the graph topology, one virtual matrix and some design parameters. Of particular interest is that if the control gain is selected appropriately, the proposed control scheme can be implemented in a unified framework no matter whether there are faults or not. Furthermore, the fault detection and isolation are not needed to implement. Finally, a simulation is given to verify the effectiveness of the proposed method.

Improved exogenous DNA uptake in bovine spermatozoa and gene expression in embryos using membrane destabilizing agents in ICSI-SMGT.

PubMed

Sánchez-Villalba, Esther; Arias, María Elena; Zambrano, Fabiola; Loren, Pía; Felmer, Ricardo

2018-02-01

Sperm-mediated gene transfer (SMGT) is a simple, fast, and economical biotechnological tool for producing transgenic animals. However, transgene expression with this technique in bovine embryos is still inefficient due to low uptake and binding of exogenous DNA in spermatozoa. The present study evaluated the effects of sperm membrane destabilization on the binding capacity, location and quantity of bound exogenous DNA in cryopreserved bovine spermatozoa using Triton X-100 (TX-100), lysolecithin (LL) and sodium hydroxide (NaOH). Effects of these treatments were also evaluated by intracytoplasmic sperm injection (ICSI)-SMGT. Results showed that all treatments bound exogenous DNA to spermatozoa including the control. Spermatozoa treated with different membrane destabilizing agents bound the exogenous DNA throughout the head and tail of spermatozoa, compared with the control, in which binding occurred mainly in the post-acrosomal region and tail. The amount of exogenous DNA bound to spermatozoa was much higher for the different sperm treatments than the control (P < 0.05), most likely due to the damage induced by these treatments to the plasma and acrosomal membranes. Exogenous gene expression in embryos was also improved by these treatments. These results demonstrated that sperm membrane destabilization could be a novel strategy in bovine SMGT protocols for the generation of transgenic embryos by ICSI.

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

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.

Effect of the antitumoral alkylating agent 3-bromopyruvate on mitochondrial respiration: role of mitochondrially bound hexokinase.

PubMed

Rodrigues-Ferreira, Clara; da Silva, Ana Paula Pereira; Galina, Antonio

2012-02-01

The alkylating agent 3-Bromopyruvate (3-BrPA) has been used as an anti-tumoral drug due to its anti-proliferative property in hepatomas cells. This propriety is believed to disturb glycolysis and respiration, which leads to a decreased rate of ATP synthesis. In this study, we evaluated the effects of the alkylating agent 3-BrPA on the respiratory states and the metabolic steps of the mitochondria of mice liver, brain and in human hepatocarcinoma cell line HepG2. The mitochondrial membrane potential (ΔΨ(m)), O(2) consumption and dehydrogenase activities were rapidly dissipated/or inhibited by 3-BrPA in respiration medium containing ADP and succinate as respiratory substrate. 3-BrPA inhibition was reverted by reduced glutathione (GSH). Respiration induced by yeast soluble hexokinase (HK) was rapidly inhibited by 3-BrPA. Similar results were observed using mice brain mitochondria that present HK naturally bound to the outer mitochondrial membrane. When the adenine nucleotide transporter (ANT) was blocked by the carboxyatractiloside, the 3-BrPA effect was significantly delayed. In permeabilized human hepatoma HepG2 cells that present HK type II bound to mitochondria (mt-HK II), the inhibiting effect occurred faster when the endogenous HK activity was activated by 2-deoxyglucose (2-DOG). Inhibition of mt-HK II by glucose-6-phosphate retards the mitochondria to react with 3-BrPA. The HK activities recovered in HepG2 cells treated or not with 3-BrPA were practically the same. These results suggest that mitochondrially bound HK supporting the ADP/ATP exchange activity levels facilitates the 3-BrPA inhibition reaction in tumors mitochondria by a proton motive force-dependent dynamic equilibrium between sensitive and less sensitive SDH in the electron transport system.

[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.

Monitoring the effects of chelating agents and electrical fields on active forms of Pb and Zn in contaminated soil.

PubMed

Tahmasbian, Iman; Safari Sinegani, Ali Akbar

2013-11-01

The application of electrical fields and chelating agents is an innovative hybrid technology used for the decontamination of soil polluted by heavy metals. The effects of four center-oriented electrical fields and chelating agents on active fractions of lead and zinc were investigated in this pot experiment. Ethylenediaminetetraacetic acid (EDTA) as a synthetic chelator and cow manure extract (CME) and poultry manure extract (PME) as natural chelators were applied to the pots (2 g kg(-1)) 30 days after the first irrigation. Two weeks later, four center-oriented electrical fields were applied in each pot (in three levels of 0, 10, and 30 V) for 1 h each day for 14 days. The soil near the cathode and anodes was collected and analyzed as cathodic and anodic soil, respectively. Results indicated that the soluble-exchangeable fraction of lead and zinc were decreased in the cathodic soil, while the carbonate-bound fractions were increased. In the anodic soil, however, the opposite result was observed. EDTA enhanced the soluble-exchangeable form of the metals in both anodic and cathodic soils. Furthermore, the amounts of carbonate-bound heavy metals were increased by the application of CME in both soils. The organic-bound fraction of the metals was increased by the application of natural chelators, while electrical fields had no significant impacts on this fraction.

Extending Romanovski polynomials in quantum mechanics

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

Quesne, C.

2013-12-15

Some extensions of the (third-class) Romanovski polynomials (also called Romanovski/pseudo-Jacobi polynomials), which appear in bound-state wavefunctions of rationally extended Scarf II and Rosen-Morse I potentials, are considered. For the former potentials, the generalized polynomials satisfy a finite orthogonality relation, while for the latter an infinite set of relations among polynomials with degree-dependent parameters is obtained. Both types of relations are counterparts of those known for conventional polynomials. In the absence of any direct information on the zeros of the Romanovski polynomials present in denominators, the regularity of the constructed potentials is checked by taking advantage of the disconjugacy properties ofmore » second-order differential equations of Schrödinger type. It is also shown that on going from Scarf I to Scarf II or from Rosen-Morse II to Rosen-Morse I potentials, the variety of rational extensions is narrowed down from types I, II, and III to type III only.« less

Bounded rationality in volunteering public goods games.

PubMed

Xu, Zhaojin; Wang, Zhen; Zhang, Lianzhong

2010-05-07

It is one of the fundamental problems in biology and social sciences how to maintain high levels of cooperation among selfish individuals. Theorists present an effective mechanism promoting cooperation by allowing for voluntary participation in public goods games. But Nash's theory predicts that no one can do better or worse than loners (players unwilling to join the public goods game) in the long run, and that the frequency of participants is independent of loners' payoff. In this paper, we introduce a degree of rationality and investigate the model by means of an approximate best response dynamics. Our research shows that the payoffs of the loners have a significant effect in anonymous voluntary public goods games by this introduction and that the dynamics will drive the system to a fixed point, which is different from the Nash equilibrium. In addition, we also qualitatively explain the existing experimental results. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Modulating bacterial and gut mucosal interactions with engineered biofilm matrix proteins.

PubMed

Duraj-Thatte, Anna M; Praveschotinunt, Pichet; Nash, Trevor R; Ward, Frederick R; Joshi, Neel S

2018-02-22

Extracellular appendages play a significant role in mediating communication between bacteria and their host. Curli fibers are a class of bacterial fimbria that is highly amenable to engineering. We demonstrate the use of engineered curli fibers to rationally program interactions between bacteria and components of the mucosal epithelium. Commensal E. coli strains were engineered to produce recombinant curli fibers fused to the trefoil family of human cytokines. Biofilms formed from these strains bound more mucins than those producing wild-type curli fibers, and modulated mucin rheology as well. When treated with bacteria producing the curli-trefoil fusions mammalian cells behaved identically in terms of their migration behavior as when they were treated with the corresponding soluble trefoil factors. Overall, this demonstrates the potential utility of curli fibers as a scaffold for the display of bioactive domains and an untapped approach to rationally modulating host-microbe interactions using bacterial matrix proteins.

A geometric modeler based on a dual-geometry representation polyhedra and rational b-splines

NASA Technical Reports Server (NTRS)

Klosterman, A. L.

1984-01-01

For speed and data base reasons, solid geometric modeling of large complex practical systems is usually approximated by a polyhedra representation. Precise parametric surface and implicit algebraic modelers are available but it is not yet practical to model the same level of system complexity with these precise modelers. In response to this contrast the GEOMOD geometric modeling system was built so that a polyhedra abstraction of the geometry would be available for interactive modeling without losing the precise definition of the geometry. Part of the reason that polyhedra modelers are effective is that all bounded surfaces can be represented in a single canonical format (i.e., sets of planar polygons). This permits a very simple and compact data structure. Nonuniform rational B-splines are currently the best representation to describe a very large class of geometry precisely with one canonical format. The specific capabilities of the modeler are described.

The original risk: overtheologizing ethics and undertheologizing sin.

PubMed

Müller, Denis

2007-01-01

The project of articulating a theological ethics on the basis of liturgical anthropology is bound to fail if the necessary consequence is that one has to quit the forum of critical modern rationality. The risk of Engelhardt's approach is to limit rationality to a narrow vision of reason. Sin is not to be understood as the negation of human holiness, but as the negation of divine holiness. The only way to renew theological ethics is to understand sin as the anthropological and ethical expression of the biblical message of the justification by faith only. Sin is therefore a secondary category, which can only by interpreted in light of the positive manifestation of liberation, justification, and grace. The central issue of Christian ethics is not ritual purity or morality, but experience, confession and recognition of our own injustice in our dealing with God and men.

A parallel-machine scheduling problem with two competing agents

NASA Astrophysics Data System (ADS)

Lee, Wen-Chiung; Chung, Yu-Hsiang; Wang, Jen-Ya

2017-06-01

Scheduling with two competing agents has become popular in recent years. Most of the research has focused on single-machine problems. This article considers a parallel-machine problem, the objective of which is to minimize the total completion time of jobs from the first agent given that the maximum tardiness of jobs from the second agent cannot exceed an upper bound. The NP-hardness of this problem is also examined. A genetic algorithm equipped with local search is proposed to search for the near-optimal solution. Computational experiments are conducted to evaluate the proposed genetic algorithm.

Rational design of avian metapneumovirus live attenuated vaccines by inhibiting viral messenger RNA cap methyltransferase

USDA-ARS?s Scientific Manuscript database

Avian metapneumovirus (aMPV), also known as avian pneumovirus or turkey rhinotracheitis, is a non-segmented negative-sense RNA virus belonging to the family of Paramyxoviridae, the subfamily Pneumovirinae, and the genus Metapneumovirus. aMPV is the causative agent of respiratory tract infection and ...

Design of a doubly-hydrophilic block copolypeptide that directs the formation of calcium carbonate microspheres.

PubMed

Euliss, Larken E; Trnka, Tina M; Deming, Timothy J; Stucky, Galen D

2004-08-07

The crystallization of calcium carbonate into microspheres has been accomplished using the rationally-designed, doubly-hydrophilic block copolypeptide poly(Nepsilon-2[2-(2-methoxyethoxy)ethoxy]acetyl-L-lysine)(100)-b-poly(L-aspartate sodium salt)30 as a structure-directing agent.

Pattern Analysis in Social Networks with Dynamic Connections

NASA Astrophysics Data System (ADS)

Wu, Yu; Zhang, Yu

In this paper, we explore how decentralized local interactions of autonomous agents in a network relate to collective behaviors. Most existing work in this area models social network in which agent relations are fixed; instead, we focus on dynamic social networks where agents can rationally adjust their neighborhoods based on their individual interests. We propose a new connection evaluation rule called the Highest Weighted Reward (HWR) rule, with which agents dynamically choose their neighbors in order to maximize their own utilities based on the rewards from previous interactions. Our experiments show that in the 2-action pure coordination game, our system will stabilize to a clustering state where all relationships in the network are rewarded with the optimal payoff. Our experiments also reveal additional interesting patterns in the network.

Topological defects in mixtures of superconducting condensates with different charges

NASA Astrophysics Data System (ADS)

Garaud, Julien; Babaev, Egor

2014-06-01

We investigate the topological defects in phenomenological models describing mixtures of charged condensates with commensurate electric charges. Such situations are expected to appear for example in liquid metallic deuterium. This is modeled by a multicomponent Ginzburg-Landau theory where the condensates are coupled to the same gauge field by different coupling constants whose ratio is a rational number. We also briefly discuss the case where electric charges are incommensurate. Flux quantization and finiteness of the energy per unit length dictate that the different condensates have different winding and thus different number of (fractional) vortices. Competing attractive and repulsive interactions lead to molecule-like bound states between fractional vortices. Such bound states have finite energy and carry integer flux quanta. These can be characterized by the CP1 topological invariant that motivates their denomination as skyrmions.

Modular constraints on conformal field theories with currents

NASA Astrophysics Data System (ADS)

Bae, Jin-Beom; Lee, Sungjay; Song, Jaewon

2017-12-01

We study constraints coming from the modular invariance of the partition function of two-dimensional conformal field theories. We constrain the spectrum of CFTs in the presence of holomorphic and anti-holomorphic currents using the semi-definite programming. In particular, we find the bounds on the twist gap for the non-current primaries depend dramatically on the presence of holomorphic currents, showing numerous kinks and peaks. Various rational CFTs are realized at the numerical boundary of the twist gap, saturating the upper limits on the degeneracies. Such theories include Wess-Zumino-Witten models for the Deligne's exceptional series, the Monster CFT and the Baby Monster CFT. We also study modular constraints imposed by W -algebras of various type and observe that the bounds on the gap depend on the choice of W -algebra in the small central charge region.

Lower bound buckling loads for design of laminate composite cylinders

NASA Astrophysics Data System (ADS)

Croll, James G. A.; Wang, Hongtao

2017-01-01

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

Targeted therapy in advanced gastric carcinoma: the future is beginning.

PubMed

Schinzari, G; Cassano, A; Orlandi, A; Basso, M; Barone, C

2014-01-01

Gastric cancer represents one of the most common cancer worldwide. Unfortunately, the majority of patients present in advanced stage and outcome still remains poor with high mortality rate despite decreasing incidence and new diagnostic and therapeutic strategies. Although utility of classical chemotherapy agents has been widely explored, advances have been slow and the efficacy of these agents has reached a plateau of median overall survival not higher than 12 months. Therefore, researchers focused their attention on better understanding molecular biology of carcinogenesis and deeper knowledge of the cancer cell phenotype, as well on development of rationally designed drugs that would target specific molecular aberrancies in signal transduction pathways. These targets include cell surface receptors, circulating growth and angiogenic factors and other molecules involved in downstream intracellular signaling pathways, including receptor tyrosine kinases. However, therapeutic advances in gastric cancer are not so encouraging when compared to other solid organ malignancies such as breast and colorectal cancer. This article reviews the role of targeted agents in gastric cancer as single-agent therapy or in combination regimens, including their rational and emerging mechanism of action, current and emerging data. We focused our attention mainly on published phase III studies, therefore cornerstone clinical trials with trastuzumab and bevacizumab have been largely discussed. Phase III studies presented in important international meetings are also reviewed as well phase II published studies and promising new therapies investigated in preclinical or phase I studies. Today, in first-line treatment only trastuzumab has shown significantly increased survival in combination with chemotherapy, whereas ramucirumab as single agent resulted effective in progressing patients, but - despite several disappointing results - these are the proof of principle that targeting the proper molecular aberration is the best way for implementing outcome of therapy.

Robust allocation of a defensive budget considering an attacker's private information.

PubMed

Nikoofal, Mohammad E; Zhuang, Jun

2012-05-01

Attackers' private information is one of the main issues in defensive resource allocation games in homeland security. The outcome of a defense resource allocation decision critically depends on the accuracy of estimations about the attacker's attributes. However, terrorists' goals may be unknown to the defender, necessitating robust decisions by the defender. This article develops a robust-optimization game-theoretical model for identifying optimal defense resource allocation strategies for a rational defender facing a strategic attacker while the attacker's valuation of targets, being the most critical attribute of the attacker, is unknown but belongs to bounded distribution-free intervals. To our best knowledge, no previous research has applied robust optimization in homeland security resource allocation when uncertainty is defined in bounded distribution-free intervals. The key features of our model include (1) modeling uncertainty in attackers' attributes, where uncertainty is characterized by bounded intervals; (2) finding the robust-optimization equilibrium for the defender using concepts dealing with budget of uncertainty and price of robustness; and (3) applying the proposed model to real data. © 2011 Society for Risk Analysis.

Structures of human ADAR2 bound to dsRNA reveal base-flipping mechanism and basis for site selectivity

DOE PAGES

Matthews, Melissa M.; Thomas, Justin M.; Zheng, Yuxuan; ...

2016-04-11

Adenosine deaminases acting on RNA (ADARs) are editing enzymes that convert adenosine to inosine in duplex RNA, a modification reaction with wide-ranging consequences in RNA function. Understanding of the ADAR reaction mechanism, the origin of editing-site selectivity, and the effect of mutations is limited by the lack of high-resolution structural data for complexes of ADARs bound to substrate RNAs. In this paper, we describe four crystal structures of the human ADAR2 deaminase domain bound to RNA duplexes bearing a mimic of the deamination reaction intermediate. These structures, together with structure-guided mutagenesis and RNA-modification experiments, explain the basis of the ADARmore » deaminase domain's dsRNA specificity, its base-flipping mechanism, and its nearest-neighbor preferences. In addition, we identified an ADAR2-specific RNA-binding loop near the enzyme active site, thus rationalizing differences in selectivity observed between different ADARs. In conclusion, our results provide a structural framework for understanding the effects of ADAR mutations associated with human disease.« less

Discovery and gram-scale synthesis of BMS-593214, a potent, selective FVIIa inhibitor

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

Priestley, E. Scott; De Lucca, Indawati; Zhou, Jinglan

A 6-amidinotetrahydroquinoline screening hit was driven to a structurally novel, potent, and selective FVIIa inhibitor through a combination of library synthesis and rational design. An efficient gram-scale synthesis of the active enantiomer BMS-593214 was developed, which required significant optimization of the key Povarov annulation. Importantly, BMS-593214 showed antithrombotic efficacy in a rabbit arterial thrombosis model. A crystal structure of BMS-593214 bound to FVIIa highlights key contacts with Asp 189, Lys 192, and the S2 pocket.

On the dynamics of disobedience: experimental investigations of defying unjust authority

PubMed Central

Bocchiaro, Piero; Zimbardo, Philip

2017-01-01

Across six Experimental conditions with university student participants (N=600), we examined some of the dynamics underlying expressed defiance to unjust authority. Results revealed disobedience was best enacted by participants low in right-wing authoritarianism and was more likely to occur when: 1) in physical proximity of other rebels, 2) the authority made two demanding requests instead of one, and 3) there had been an earlier opposition to injustice. Results are discussed within the theoretical framework of bounded rationality. PMID:28761383

On the dynamics of disobedience: experimental investigations of defying unjust authority.

PubMed

Bocchiaro, Piero; Zimbardo, Philip

2017-01-01

Across six Experimental conditions with university student participants (N=600), we examined some of the dynamics underlying expressed defiance to unjust authority. Results revealed disobedience was best enacted by participants low in right-wing authoritarianism and was more likely to occur when: 1) in physical proximity of other rebels, 2) the authority made two demanding requests instead of one, and 3) there had been an earlier opposition to injustice. Results are discussed within the theoretical framework of bounded rationality.

The Changing Strategic Balance and US Defense Planning.

DTIC Science & Technology

1984-02-01

that ’,+, :., -nuclear war is unthinkable and that the application of force is V 3 prima facie evidence of failure of rational analysis and patient...University. Dr. Kennedy served on active duty briefly with the Army and !hen with the Air Force from 1958 to 1971 and is currently a reserve officer...pursuing a war-winning capability designed to give them a strategic advantage they woule be " duty bound" to exploit." In the wake of his participation

A smart T(1)-weighted MRI contrast agent for uranyl cations based on a DNAzyme-gadolinium conjugate.

PubMed

Xu, Weichen; Xing, Hang; Lu, Yi

2013-11-07

Rational design of smart MRI contrast agents with high specificity for metal ions remains a challenge. Here, we report a general strategy for the design of smart MRI contrast agents for detecting metal ions based on conjugation of a DNAzyme with a gadolinium complex. The 39E DNAzyme, which has high selectivity for UO2(2+), was conjugated to Gd(III)-DOTA and streptavidin. The binding of UO2(2+) to its 39E DNAzyme resulted in the dissociation of Gd(III)-DOTA from the large streptavidin, leading to a decrease of the T1 correlation time, and a change in the MRI signal.

Detoxification of organophosphate nerve agents by bacterial phosphotriesterase

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

Ghanem, Eman; Raushel, Frank M.

2005-09-01

Organophosphates have been widely used as insecticides and chemical warfare agents. The health risks associated with these agents have necessitated the need for better detoxification and bioremediation tools. Bacterial enzymes capable of hydrolyzing the lethal organophosphate nerve agents are of special interest. Phosphotriesterase (PTE) isolated from the soil bacteria Pseudomonas diminuta displays a significant rate enhancement and substrate promiscuity for the hydrolysis of organophosphate triesters. Directed evolution and rational redesign of the active site of PTE have led to the identification of new variants with enhanced catalytic efficiency and stereoselectivity toward the hydrolysis of organophosphate neurotoxins. PTE has been utilizedmore » to protect against organophosphate poisoning in vivo. Biotechnological applications of PTE for detection and decontamination of insecticides and chemical warfare agents are developing into useful tools. In this review, the catalytic properties and potential applications of this remarkable enzyme are discussed.« less

X-ray structures define human P2X3 receptor gating cycle and antagonist action

PubMed Central

Mansoor, Steven E.; Lü, Wei; Oosterheert, Wout; Shekhar, Mrinal; Tajkhorshid, Emad; Gouaux, Eric

2016-01-01

Summary P2X receptors are trimeric, non-selective cation channels activated by ATP that play important roles in cardiovascular, neuronal and immune systems. Despite their central function in human physiology and as potential targets of therapeutic agents, there are no structures of human P2X receptors. Mechanisms of receptor desensitization and ion permeation, principles of antagonism, and complete structure of the pore-forming transmembrane domains remain unclear. We report x-ray crystal structures of human P2X3 receptor in apo/resting, agonist-bound/open-pore, agonist-bound/desensitized and antagonist-bound closed states. The open state structure harbors an intracellular motif we term the “cytoplasmic cap”, that stabilizes the open state of the ion channel pore and creates lateral, phospholipid-lined cytoplasmic fenestrations for water and ion egress. Competitive antagonists TNP-ATP and A-317491 stabilize the apo/resting state and reveal the interactions responsible for competitive inhibition. These structures illuminate the conformational rearrangements underpinning P2X receptor gating and provide a foundation for development of new pharmacologic agents. PMID:27626375

Observer-based distributed adaptive fault-tolerant containment control of multi-agent systems with general linear dynamics.

PubMed

Ye, Dan; Chen, Mengmeng; Li, Kui

2017-11-01

In this paper, we consider the distributed containment control problem of multi-agent systems with actuator bias faults based on observer method. The objective is to drive the followers into the convex hull spanned by the dynamic leaders, where the input is unknown but bounded. By constructing an observer to estimate the states and bias faults, an effective distributed adaptive fault-tolerant controller is developed. Different from the traditional method, an auxiliary controller gain is designed to deal with the unknown inputs and bias faults together. Moreover, the coupling gain can be adjusted online through the adaptive mechanism without using the global information. Furthermore, the proposed control protocol can guarantee that all the signals of the closed-loop systems are bounded and all the followers converge to the convex hull with bounded residual errors formed by the dynamic leaders. Finally, a decoupled linearized longitudinal motion model of the F-18 aircraft is used to demonstrate the effectiveness. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

Polymer blend compositions and methods of preparation

DOEpatents

Naskar, Amit K.

2016-09-27

A polymer blend material comprising: (i) a first polymer containing hydrogen bond donating groups having at least one hydrogen atom bound to a heteroatom selected from oxygen, nitrogen, and sulfur, or an anionic version of said first polymer wherein at least a portion of hydrogen atoms bound to a heteroatom is absent and replaced with at least one electron pair; (ii) a second polymer containing hydrogen bond accepting groups selected from nitrile, halogen, and ether functional groups; and (iii) at least one modifying agent selected from carbon particles, ether-containing polymers, and Lewis acid compounds; wherein, if said second polymer contains ether functional groups, then said at least one modifying agent is selected from carbon particles and Lewis acid compounds. Methods for producing the polymer blend, molded forms thereof, and articles thereof, are also described.

Chemical Peels in Melasma: A Review with Consensus Recommendations by Indian Pigmentary Expert Group.

PubMed

Sarkar, Rashmi; Arsiwala, Shehnaz; Dubey, Neha; Sonthalia, Sidharth; Das, Anupam; Arya, Latika; Gokhale, Narendra; Torsekar, R G; Somani, V K; Majid, Imran; Godse, Kiran; Ravichandran, G; Singh, Mohan; Aurangabadkar, Sanjeev; Salim, T; Shah, Swapnil; Sinha, Surabhi

2017-01-01

Melasma is a notorious dermatosis, often resistant to treatment. Chemical peeling constitutes an acceptable option of management of melasma (of any type and duration). In this article, as a group of experts from Pigmentary Disorders Society (PDS) in collaboration with South Asian Pigmentary Forum (SPF), we have tried to elaborate the various chemical peeling agents for the treatment of melasma. Besides, we have reviewed the indications, mechanism of action, rationality and the detailed procedure of peeling. The evidence in favor of various peeling agents have been summarized as well.

Price dynamics of the financial markets using the stochastic differential equation for a potential double well

NASA Astrophysics Data System (ADS)

Lima, L. S.; Miranda, L. L. B.

2018-01-01

We have used the Itô's stochastic differential equation for the double well with additive white noise as a mathematical model for price dynamics of the financial market. We have presented a model which allows us to test within the same framework the comparative explanatory power of rational agents versus irrational agents, with respect to the facts of financial markets. We have obtained the mean price in terms of the β parameter that represents the force of the randomness term of the model.

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

PubMed

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

2012-11-01

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

Inhibition of Btk with CC-292 provides early pharmacodynamic assessment of activity in mice and humans.

PubMed

Evans, Erica K; Tester, Richland; Aslanian, Sharon; Karp, Russell; Sheets, Michael; Labenski, Matthew T; Witowski, Steven R; Lounsbury, Heather; Chaturvedi, Prasoon; Mazdiyasni, Hormoz; Zhu, Zhendong; Nacht, Mariana; Freed, Martin I; Petter, Russell C; Dubrovskiy, Alex; Singh, Juswinder; Westlin, William F

2013-08-01

Targeted therapies that suppress B cell receptor (BCR) signaling have emerged as promising agents in autoimmune disease and B cell malignancies. Bruton's tyrosine kinase (Btk) plays a crucial role in B cell development and activation through the BCR signaling pathway and represents a new target for diseases characterized by inappropriate B cell activity. N-(3-(5-fluoro-2-(4-(2-methoxyethoxy)phenylamino)pyrimidin-4-ylamino)phenyl)acrylamide (CC-292) is a highly selective, covalent Btk inhibitor and a sensitive and quantitative assay that measures CC-292-Btk engagement has been developed. This translational pharmacodynamic assay has accompanied CC-292 through each step of drug discovery and development. These studies demonstrate the quantity of Btk bound by CC-292 correlates with the efficacy of CC-292 in vitro and in the collagen-induced arthritis model of autoimmune disease. Recently, CC-292 has entered human clinical trials with a trial design that has provided rapid insight into safety, pharmacokinetics, and pharmacodynamics. This first-in-human healthy volunteer trial has demonstrated that a single oral dose of 2 mg/kg CC-292 consistently engaged all circulating Btk protein and provides the basis for rational dose selection in future clinical trials. This targeted covalent drug design approach has enabled the discovery and early clinical development of CC-292 and has provided support for Btk as a valuable drug target for B-cell mediated disorders.

Synthetic Motors and Nanomachines.

NASA Astrophysics Data System (ADS)

Flood, Amar

2006-03-01

A bistable and palindromically-constituted [3]rotaxane incorporating two mechanically-mobile rings interlocked around a linear dumbbell component, has been designed to operate like the sarcomeres of skeletal muscle. Contraction and extension occurs when the inter-ring distance of the two rings switch, ideally, between 4.2 and 1.4 nm upon redox stimulation either chemically or electrochemically in the solution phase. When the mobile rings of these artificial molecular muscles are bound onto the tops of gold-coated, micron-scale cantilever beams, their controllable nanometer motions have a chance to be amplified along the long axis of each cantilever. It turns out that ˜6 billion of the self-assembled [3]rotaxanes can bend the cantilevers in a bistable manner concomitant with the cycled addition of redox agents. The extent of bending is commensurate with 10's of pN of force per [3]rotaxane. Recent studies on a set of ``single-shot'' control [2]rotaxanes have provided additional evidence for the origins of the force generation as it arises from a molecule-based electrostatic repulsion energy of about 10 kcal/mol at 300 K. These findings will be presented in terms of the underlying thermodynamics and kinetics that have been utilized extensively to direct the design and synthesis of artificial molecular machines and which may also serve as a guide for the rational design of unidirectional molecular motors.

Robust Architectures for Complex Multi-Agent Heterogeneous Systems

DTIC Science & Technology

2014-07-23

establish the tradeoff between the control performance and the QoS of the communications network . We also derived the performance bound on the difference...accomplished within this time period leveraged the prior accomplishments in the area of networked multi-agent systems. The past work (prior to 2011...distributed control of uncertain networked systems [3]. Additionally, a preliminary collision avoidance algorithm has been developed for a team of

Integrated Optic Chemical-Biological Sensors

DTIC Science & Technology

1999-02-26

response. In this process, an enzyme ( urease ) acts as a catalyst, converting a specific substrate (urea) to a specific product (ammonia). Implementing...a sandwich assay, a urease labeled antibody is introduced to a surface bound antigen. This complex is exposed to urea, generating ammonia. Using a...containing suspected agents. After agent binding to the antibody-coated beads, an appropriate enzyme labeled antibody (an antibody with a urease label

A Rational Analysis of the Effects of Memory Biases on Serial Reproduction

ERIC Educational Resources Information Center

Xu, Jing; Griffiths, Thomas L.

2010-01-01

Many human interactions involve pieces of information being passed from one person to another, raising the question of how this process of information transmission is affected by the cognitive capacities of the agents involved. Bartlett (1932) explored the influence of memory biases on the "serial reproduction" of information, in which one…

Family Background, Self-Confidence and Economic Outcomes

ERIC Educational Resources Information Center

Filippin, Antonio; Paccagnella, Marco

2012-01-01

In this paper we analyze the role played by self-confidence, modeled as beliefs about one's ability, in shaping task choices. We propose a model in which fully rational agents exploit all the available information to update their beliefs using Bayes' rule, eventually learning their true type. We show that when the learning process does not…

Metabolism and Resistance of Fusarium spp. to the Manzamine Alkaloids via a Putative Retro Pictet-Spengler Reaction and Utility of the Rational Design of Antimalarial and Antifungal Agents

PubMed Central

Farr, Lorelei Lucas; Gholipour, Abbas; Wedge, David E.; Hamann, Mark T.

2014-01-01

As a part of our continuing investigation of the manzamine alkaloids we studied the in vitro activity of the β-carboline containing manzamine alkaloids against Fusarium solani, Fusarium oxysporium, and Fusarium proliferatum by employing several bioassay techniques including one-dimensional direct bioautography, dilution, and plate susceptibility, and microtiter broth assays. In addition, we also studied the metabolism of the manzamine alkaloids by Fusarium spp. in order to facilitate the redesign of the compounds to prevent resistance of Fusarium spp. through metabolism. The present research reveals that the manzamine alkaloids are inactive against Fusarium spp. and the fungi transform manzamines via hydrolysis, reduction, and a retro Pictet-Spengler reaction. This is the first report to demonstrate an enzymatically retro Pictet-Spengler reaction. The results of this study reveal the utility of the rational design of metabolically stable antifungal agents from this class and the development of manzamine alkaloids as antimalarial drugs through the utilization of Fusarium’s metabolic products to reconstruct the molecule. PMID:24553735

Evolving the capacity to understand actions, intentions, and goals.

PubMed

Hauser, Marc; Wood, Justin

2010-01-01

We synthesize the contrasting predictions of motor simulation and teleological theories of action comprehension and present evidence from a series of studies showing that monkeys and apes-like humans-extract the meaning of an event by (a) going beyond the surface appearance of actions, attributing goals and intentions to the agent; (b) using details about the environment to infer when an action is rational or irrational; (c) making predictions about an agent's goal and the most probable action to obtain the goal, within the constraints of the situation; (d) predicting the most probable outcome of actions even when they are physiologically incapable of producing the actions; and (e) combining information about means and outcomes to make decisions about social interactions, some with moral relevance. These studies reveal the limitations of motor simulation theories, especially those that rely on the notion of direct matching and mirror neuron activation. They provide support, however, for a teleological theory, rooted in an inferential process that extracts information about action means, potential goals, and the environmental constraints that limit rational action.

Interaction of staphylococcal delta-toxin and synthetic analogues with erythrocytes and phospholipid vesicles. Biological and physical properties of the amphipathic peptides.

PubMed

Alouf, J E; Dufourcq, J; Siffert, O; Thiaudiere, E; Geoffroy, C

1989-08-01

Staphylococcal delta-toxin, a 26-residue amphiphilic peptide is lytic for cells and phospholipid vesicles and is assumed to insert as an amphipathic helix and oligomerize in membranes. For the first time, the relationship between these properties and toxin structure is investigated by means of eight synthetic peptides, one identical in sequence to the natural toxin, five 26-residue analogues and two shorter peptides corresponding to residues 1-11 and 11-26. These peptides were designed by the Edmundson wheel axial projection in order to maintain: (a) the hydrophilic/hydrophobic balance while rationalizing the sequence, (b) the alpha-helical configuration and (c) the common epitopic structure. The fluorescence of the single Trp residue was used to monitor the behaviour of the natural toxin and analogues. All 26-residue analogues were hemolytically active although to a lesser extent than natural toxin. The peptide of residues 11-26 bound lipids weakly and was hemolytic at high concentration. The peptide of residues 1-11 did not bind lipids and was hemolytically inactive. All peptides except the latter cross-reacted in immunoprecipitation tests with the natural toxin. The study of a 26-residue analogue by circular dichroism revealed an alpha-helical configuration in both the free and lipid-bound state. Changes in the fluorescence of the peptides in the presence of lipid micelles and bilayers varied according to the position of the reporter group. When bound to lipids, Trp5, Trp16 and the Fmoc-1 positions of the analogues became buried while Trp15 of the natural toxin and its synthetic replicate remained more exposed. All changes are rationalized by the proposal of an amphipathic helix whose hydrophobic face is embedded within the apolar core of bilayers while the hydrophilic and charged face remains more exposed to solvent.

An Extended Chemical Plant Environmental Protection Game on Addressing Uncertainties of Human Adversaries.

PubMed

Zhu, Zhengqiu; Chen, Bin; Qiu, Sihang; Wang, Rongxiao; Chen, Feiran; Wang, Yiping; Qiu, Xiaogang

2018-03-27

Chemical production activities in industrial districts pose great threats to the surrounding atmospheric environment and human health. Therefore, developing appropriate and intelligent pollution controlling strategies for the management team to monitor chemical production processes is significantly essential in a chemical industrial district. The literature shows that playing a chemical plant environmental protection (CPEP) game can force the chemical plants to be more compliant with environmental protection authorities and reduce the potential risks of hazardous gas dispersion accidents. However, results of the current literature strictly rely on several perfect assumptions which rarely hold in real-world domains, especially when dealing with human adversaries. To address bounded rationality and limited observability in human cognition, the CPEP game is extended to generate robust schedules of inspection resources for inspection agencies. The present paper is innovative on the following contributions: (i) The CPEP model is extended by taking observation frequency and observation cost of adversaries into account, and thus better reflects the industrial reality; (ii) Uncertainties such as attackers with bounded rationality, attackers with limited observation and incomplete information (i.e., the attacker's parameters) are integrated into the extended CPEP model; (iii) Learning curve theory is employed to determine the attacker's observability in the game solver. Results in the case study imply that this work improves the decision-making process for environmental protection authorities in practical fields by bringing more rewards to the inspection agencies and by acquiring more compliance from chemical plants.

Concepts and Bounded Rationality: An Application of Niestegge's Approach to Conditional Quantum Probabilities

NASA Astrophysics Data System (ADS)

Blutner, Reinhard

2009-03-01

Recently, Gerd Niestegge developed a new approach to quantum mechanics via conditional probabilities developing the well-known proposal to consider the Lüders-von Neumann measurement as a non-classical extension of probability conditionalization. I will apply his powerful and rigorous approach to the treatment of concepts using a geometrical model of meaning. In this model, instances are treated as vectors of a Hilbert space H. In the present approach there are at least two possibilities to form categories. The first possibility sees categories as a mixture of its instances (described by a density matrix). In the simplest case we get the classical probability theory including the Bayesian formula. The second possibility sees categories formed by a distinctive prototype which is the superposition of the (weighted) instances. The construction of prototypes can be seen as transferring a mixed quantum state into a pure quantum state freezing the probabilistic characteristics of the superposed instances into the structure of the formed prototype. Closely related to the idea of forming concepts by prototypes is the existence of interference effects. Such inference effects are typically found in macroscopic quantum systems and I will discuss them in connection with several puzzles of bounded rationality. The present approach nicely generalizes earlier proposals made by authors such as Diederik Aerts, Andrei Khrennikov, Ricardo Franco, and Jerome Busemeyer. Concluding, I will suggest that an active dialogue between cognitive approaches to logic and semantics and the modern approach of quantum information science is mandatory.

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.

An Extended Chemical Plant Environmental Protection Game on Addressing Uncertainties of Human Adversaries

PubMed Central

Wang, Rongxiao; Chen, Feiran; Wang, Yiping; Qiu, Xiaogang

2018-01-01

Chemical production activities in industrial districts pose great threats to the surrounding atmospheric environment and human health. Therefore, developing appropriate and intelligent pollution controlling strategies for the management team to monitor chemical production processes is significantly essential in a chemical industrial district. The literature shows that playing a chemical plant environmental protection (CPEP) game can force the chemical plants to be more compliant with environmental protection authorities and reduce the potential risks of hazardous gas dispersion accidents. However, results of the current literature strictly rely on several perfect assumptions which rarely hold in real-world domains, especially when dealing with human adversaries. To address bounded rationality and limited observability in human cognition, the CPEP game is extended to generate robust schedules of inspection resources for inspection agencies. The present paper is innovative on the following contributions: (i) The CPEP model is extended by taking observation frequency and observation cost of adversaries into account, and thus better reflects the industrial reality; (ii) Uncertainties such as attackers with bounded rationality, attackers with limited observation and incomplete information (i.e., the attacker’s parameters) are integrated into the extended CPEP model; (iii) Learning curve theory is employed to determine the attacker’s observability in the game solver. Results in the case study imply that this work improves the decision-making process for environmental protection authorities in practical fields by bringing more rewards to the inspection agencies and by acquiring more compliance from chemical plants. PMID:29584679

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.

The role of noise in the spatial public goods game

NASA Astrophysics Data System (ADS)

Javarone, Marco Alberto; Battiston, Federico

2016-07-01

In this work we aim to analyze the role of noise in the spatial public goods game, one of the most famous games in evolutionary game theory. The dynamics of this game is affected by a number of parameters and processes, namely the topology of interactions among the agents, the synergy factor, and the strategy revision phase. The latter is a process that allows agents to change their strategy. Notably, rational agents tend to imitate richer neighbors, in order to increase the probability to maximize their payoff. By implementing a stochastic revision process, it is possible to control the level of noise in the system, so that even irrational updates may occur. In particular, in this work we study the effect of noise on the macroscopic behavior of a finite structured population playing the public goods game. We consider both the case of a homogeneous population, where the noise in the system is controlled by tuning a parameter representing the level of stochasticity in the strategy revision phase, and a heterogeneous population composed of a variable proportion of rational and irrational agents. In both cases numerical investigations show that the public goods game has a very rich behavior which strongly depends on the amount of noise in the system and on the value of the synergy factor. To conclude, our study sheds a new light on the relations between the microscopic dynamics of the public goods game and its macroscopic behavior, strengthening the link between the field of evolutionary game theory and statistical physics.

Do framing effects reveal irrational choice?

PubMed

Mandel, David R

2014-06-01

Framing effects have long been viewed as compelling evidence of irrationality in human decision making, yet that view rests on the questionable assumption that numeric quantifiers used to convey the expected values of choice options are uniformly interpreted as exact values. Two experiments show that when the exactness of such quantifiers is made explicit by the experimenter, framing effects vanish. However, when the same quantifiers are given a lower bound (at least) meaning, the typical framing effect is found. A 3rd experiment confirmed that most people spontaneously interpret the quantifiers in standard framing tests as lower bounded and that their interpretations strongly moderate the framing effect. Notably, in each experiment, a significant majority of participants made rational choices, either choosing the option that maximized expected value (i.e., lives saved) or choosing consistently across frames when the options were of equal expected value. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Designed Long‐Lived Emission from CdSe Quantum Dots through Reversible Electronic Energy Transfer with a Surface‐Bound Chromophore

PubMed Central

La Rosa, Marcello; Denisov, Sergey A.

2018-01-01

Abstract The size‐tunable emission of luminescent quantum dots (QDs) makes them highly interesting for applications that range from bioimaging to optoelectronics. For the same applications, engineering their luminescence lifetime, in particular, making it longer, would be as important; however, no rational approach to reach this goal is available to date. We describe a strategy to prolong the emission lifetime of QDs through electronic energy shuttling to the triplet excited state of a surface‐bound molecular chromophore. To implement this idea, we made CdSe QDs of different sizes and carried out self‐assembly with a pyrene derivative. We observed that the conjugates exhibit delayed luminescence, with emission decays that are prolonged by more than 3 orders of magnitude (lifetimes up to 330 μs) compared to the parent CdSe QDs. The mechanism invokes unprecedented reversible quantum dot to organic chromophore electronic energy transfer. PMID:29383800

Molecular targeting of growth factor receptor-bound 2 (Grb2) as an anti-cancer strategy.

PubMed

Dharmawardana, Pathirage G; Peruzzi, Benedetta; Giubellino, Alessio; Burke, Terrence R; Bottaro, Donald P

2006-01-01

Growth factor receptor-bound 2 (Grb2) is a ubiquitously expressed adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway. As such, it has been implicated in the oncogenesis of several important human malignancies. In addition to this function, research over the last decade has revealed other fundamental roles for Grb2 in cell motility and angiogenesis--processes that also contribute to tumor growth, invasiveness and metastasis. This functional profile makes Grb2 a high priority target for anti-cancer drug development. Knowledge of Grb2 protein structure, its component Src homology domains and their respective structure-function relationships has facilitated the rapid development of sophisticated drug candidates that can penetrate cells, bind Grb2 with high affinity and potently antagonize Grb2 signaling. These novel compounds offer considerable promise in our growing arsenal of rationally designed anti-cancer therapeutics.

Finite-time and fixed-time leader-following consensus for multi-agent systems with discontinuous inherent dynamics

NASA Astrophysics Data System (ADS)

Ning, Boda; Jin, Jiong; Zheng, Jinchuan; Man, Zhihong

2018-06-01

This paper is concerned with finite-time and fixed-time consensus of multi-agent systems in a leader-following framework. Different from conventional leader-following tracking approaches where inherent dynamics satisfying the Lipschitz continuous condition is required, a more generalised case is investigated: discontinuous inherent dynamics. By nonsmooth techniques, a nonlinear protocol is first proposed to achieve the finite-time leader-following consensus. Then, based on fixed-time stability strategies, the fixed-time leader-following consensus problem is solved. An upper bound of settling time is obtained by using a new protocol, and such a bound is independent of initial states, thereby providing additional options for designers in practical scenarios where initial conditions are unavailable. Finally, numerical simulations are provided to demonstrate the effectiveness of the theoretical results.

Exact solution of a modified El Farol's bar problem: Efficiency and the role of market impact

NASA Astrophysics Data System (ADS)

Marsili, Matteo; Challet, Damien; Zecchina, Riccardo

2000-06-01

We discuss a model of heterogeneous, inductive rational agents inspired by the El Farol Bar problem and the Minority Game. As in markets, agents interact through a collective aggregate variable - which plays a role similar to price - whose value is fixed by all of them. Agents follow a simple reinforcement-learning dynamics where the reinforcement, for each of their available strategies, is related to the payoff delivered by that strategy. We derive the exact solution of the model in the “thermodynamic” limit of infinitely many agents using tools of statistical physics of disordered systems. Our results show that the impact of agents on the market price plays a key role: even though price has a weak dependence on the behavior of each individual agent, the collective behavior crucially depends on whether agents account for such dependence or not. Remarkably, if the adaptive behavior of agents accounts even “infinitesimally” for this dependence they can, in a whole range of parameters, reduce global fluctuations by a finite amount. Both global efficiency and individual utility improve with respect to a “price taker” behavior if agents account for their market impact.

Uncertainty in a spatial evacuation model

NASA Astrophysics Data System (ADS)

Mohd Ibrahim, Azhar; Venkat, Ibrahim; Wilde, Philippe De

2017-08-01

Pedestrian movements in crowd motion can be perceived in terms of agents who basically exhibit patient or impatient behavior. We model crowd motion subject to exit congestion under uncertainty conditions in a continuous space and compare the proposed model via simulations with the classical social force model. During a typical emergency evacuation scenario, agents might not be able to perceive with certainty the strategies of opponents (other agents) owing to the dynamic changes entailed by the neighborhood of opponents. In such uncertain scenarios, agents will try to update their strategy based on their own rules or their intrinsic behavior. We study risk seeking, risk averse and risk neutral behaviors of such agents via certain game theory notions. We found that risk averse agents tend to achieve faster evacuation time whenever the time delay in conflicts appears to be longer. The results of our simulations also comply with previous work and conform to the fact that evacuation time of agents becomes shorter once mutual cooperation among agents is achieved. Although the impatient strategy appears to be the rational strategy that might lead to faster evacuation times, our study scientifically shows that the more the agents are impatient, the slower is the egress time.

Non-thermal transitions in a model inspired by moral decisions

NASA Astrophysics Data System (ADS)

Alamino, Roberto C.

2016-08-01

This work introduces a model in which agents of a network act upon one another according to three different kinds of moral decisions. These decisions are based on an increasing level of sophistication in the empathy capacity of the agent, a hierarchy which we name Piaget’s ladder. The decision strategy of the agents is non-rational, in the sense they are arbitrarily fixed, and the model presents quenched disorder given by the distribution of its defining parameters. An analytical solution for this model is obtained in the large system limit as well as a leading order correction for finite-size systems which shows that typical realisations of the model develop a phase structure with both continuous and discontinuous non-thermal transitions.

The impact of "omic" and imaging technologies on assessing the host immune response to biodefence agents.

PubMed

Tree, Julia A; Flick-Smith, Helen; Elmore, Michael J; Rowland, Caroline A

2014-01-01

Understanding the interactions between host and pathogen is important for the development and assessment of medical countermeasures to infectious agents, including potential biodefence pathogens such as Bacillus anthracis, Ebola virus, and Francisella tularensis. This review focuses on technological advances which allow this interaction to be studied in much greater detail. Namely, the use of "omic" technologies (next generation sequencing, DNA, and protein microarrays) for dissecting the underlying host response to infection at the molecular level; optical imaging techniques (flow cytometry and fluorescence microscopy) for assessing cellular responses to infection; and biophotonic imaging for visualising the infectious disease process. All of these technologies hold great promise for important breakthroughs in the rational development of vaccines and therapeutics for biodefence agents.

Novel Approaches for Targeting Antiviral Agents in the Treatment of Arena-, Bunya-, Flavi-, and Retroviral Infections

DTIC Science & Technology

1989-05-22

potentially useful antivirals (e... S-HMPA, selenazole, WIN 5177, arildone, phosphonoformic acid ) are currently under investigation. There are, however...by increasing dosage, this often results in toxicity. For example, a number of antiviral agents (ribavirin, adenine arabinoside, phosphonoformic acid ...Three possibilities exist for the activation of carrier bound drugs: 1) endocytosis and release in acidic endosomes; 2) extracellular activation at cell

Rational non-interventional paternalism: why doctors ought to make judgments of what is best for their patients.

PubMed

Savulescu, J

1995-12-01

This paper argues that doctors ought to make all things considered value judgments about what is best for their patients. It illustrates some of the shortcomings of the model of doctor as 'fact-provider'. The 'fact-provider' model fails to take account of the fact that practising medicine necessarily involves making value judgments; that medical practice is a moral practice and requires that doctors reflect on what ought to be done, and that patients can make choices which fail to express their autonomy and which are based on mistaken judgments of value. If doctors are properly to respect patient autonomy and to function as moral agents, they must make evaluations of what their patients ought to do, all things considered. This paper argues for 'rational, non-interventional paternalism'. This is a practice in which doctors form conceptions of what is best for their patients and argue rationally with them. It differs from old-style paternalism in that it is not committed to doing what is best.

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.

Influence of glucagon or 5-(tetradecyloxy)-2-furoic acid on binding to mitochondria and phosphorylation of ATP-citrate lyase.

PubMed

Janski, A M; Cornell, N W

1982-02-01

To study the binding to mitochondria and the phosphorylation of ATP-citrate lyase (EC 4.1.3.8), isolated rat hepatocytes were fractionated by exposure to digitonin. After incubation of hepatocytes with the hypolipidemic agent 5-(tetradecyloxy)-2-furoic acid, which decreases the cellular CoA, the amount of bound ATP-citrate lyase was increased, but the content of acid-stable phosphate in the enzyme was diminished. Glucagon, in contrast, decreased the amount of bound enzyme but increased phosphorylation. This inverse relationship might indicate either that the bound ATP-citrate lyase is less readily phosphorylated or that the phosphorylated enzyme binds less readily to mitochondria.

Chemical Peels in Melasma: A Review with Consensus Recommendations by Indian Pigmentary Expert Group

PubMed Central

Sarkar, Rashmi; Arsiwala, Shehnaz; Dubey, Neha; Sonthalia, Sidharth; Das, Anupam; Arya, Latika; Gokhale, Narendra; Torsekar, RG; Somani, VK; Majid, Imran; Godse, Kiran; Ravichandran, G.; Singh, Mohan; Aurangabadkar, Sanjeev; Salim, T; Shah, Swapnil; Sinha, Surabhi

2017-01-01

Melasma is a notorious dermatosis, often resistant to treatment. Chemical peeling constitutes an acceptable option of management of melasma (of any type and duration). In this article, as a group of experts from Pigmentary Disorders Society (PDS) in collaboration with South Asian Pigmentary Forum (SPF), we have tried to elaborate the various chemical peeling agents for the treatment of melasma. Besides, we have reviewed the indications, mechanism of action, rationality and the detailed procedure of peeling. The evidence in favor of various peeling agents have been summarized as well. PMID:29263530

Evolutionary Games in Multi-Agent Systems of Weighted Social Networks

NASA Astrophysics Data System (ADS)

Du, Wen-Bo; Cao, Xian-Bin; Zheng, Hao-Ran; Zhou, Hong; Hu, Mao-Bin

Much empirical evidence has shown realistic networks are weighted. Compared with those on unweighted networks, the dynamics on weighted network often exhibit distinctly different phenomena. In this paper, we investigate the evolutionary game dynamics (prisoner's dilemma game and snowdrift game) on a weighted social network consisted of rational agents and focus on the evolution of cooperation in the system. Simulation results show that the cooperation level is strongly affected by the weighted nature of the network. Moreover, the variation of time series has also been investigated. Our work may be helpful in understanding the cooperative behavior in the social systems.

Net-Centric Information and Knowledge Management and Dissemination for Data-to-Decision C2 Applications Using Intelligent Agents and Service-Oriented Architectures

DTIC Science & Technology

2011-11-01

data. s to make time rations. TITA lish and Subs ge messages i y FBCB2 and y gathering an rt tactical deci ontinuous asse s, including ions through...well as one ad from data-t y spans multip and control command (M red, Fused, a eports. (BCW) tric agent-bas y from TITA sts to dismoun...new ong all TITA current state of nit, and proces emination Sup ge transport s echelons a ort mechanis mentation of X le dynamic n alized or a pur

Clinical reasoning in the real world is mediated by bounded rationality: implications for diagnostic clinical practice guidelines.

PubMed

Bonilauri Ferreira, Ana Paula Ribeiro; Ferreira, Rodrigo Fernando; Rajgor, Dimple; Shah, Jatin; Menezes, Andrea; Pietrobon, Ricardo

2010-04-20

Little is known about the reasoning mechanisms used by physicians in decision-making and how this compares to diagnostic clinical practice guidelines. We explored the clinical reasoning process in a real life environment. This is a qualitative study evaluating transcriptions of sixteen physicians' reasoning during appointments with patients, clinical discussions between specialists, and personal interviews with physicians affiliated to a hospital in Brazil. FOUR MAIN THEMES WERE IDENTIFIED: simple and robust heuristics, extensive use of social environment rationality, attempts to prove diagnostic and therapeutic hypothesis while refuting potential contradictions using positive test strategy, and reaching the saturation point. Physicians constantly attempted to prove their initial hypothesis while trying to refute any contradictions. While social environment rationality was the main factor in the determination of all steps of the clinical reasoning process, factors such as referral letters and number of contradictions associated with the initial hypothesis had influence on physicians' confidence and determination of the threshold to reach a final decision. Physicians rely on simple heuristics associated with environmental factors. This model allows for robustness, simplicity, and cognitive energy saving. Since this model does not fit into current diagnostic clinical practice guidelines, we make some propositions to help its integration.

Clinical Reasoning in the Real World Is Mediated by Bounded Rationality: Implications for Diagnostic Clinical Practice Guidelines

PubMed Central

Bonilauri Ferreira, Ana Paula Ribeiro; Ferreira, Rodrigo Fernando; Rajgor, Dimple; Shah, Jatin; Menezes, Andrea; Pietrobon, Ricardo

2010-01-01

Background Little is known about the reasoning mechanisms used by physicians in decision-making and how this compares to diagnostic clinical practice guidelines. We explored the clinical reasoning process in a real life environment. Method This is a qualitative study evaluating transcriptions of sixteen physicians' reasoning during appointments with patients, clinical discussions between specialists, and personal interviews with physicians affiliated to a hospital in Brazil. Results Four main themes were identified: simple and robust heuristics, extensive use of social environment rationality, attempts to prove diagnostic and therapeutic hypothesis while refuting potential contradictions using positive test strategy, and reaching the saturation point. Physicians constantly attempted to prove their initial hypothesis while trying to refute any contradictions. While social environment rationality was the main factor in the determination of all steps of the clinical reasoning process, factors such as referral letters and number of contradictions associated with the initial hypothesis had influence on physicians' confidence and determination of the threshold to reach a final decision. Discussion Physicians rely on simple heuristics associated with environmental factors. This model allows for robustness, simplicity, and cognitive energy saving. Since this model does not fit into current diagnostic clinical practice guidelines, we make some propositions to help its integration. PMID:20421920

Sacred bounds on rational resolution of violent political conflict

PubMed Central

Ginges, Jeremy; Atran, Scott; Medin, Douglas; Shikaki, Khalil

2007-01-01

We report a series of experiments carried out with Palestinian and Israeli participants showing that violent opposition to compromise over issues considered sacred is (i) increased by offering material incentives to compromise but (ii) decreased when the adversary makes symbolic compromises over their own sacred values. These results demonstrate some of the unique properties of reasoning and decision-making over sacred values. We show that the use of material incentives to promote the peaceful resolution of political and cultural conflicts may backfire when adversaries treat contested issues as sacred values. PMID:17460042

Testing the Human Capital Development Model: The Case of Apprenticeships in Turkey

ERIC Educational Resources Information Center

Akpinar, Taner; Gün, Servet

2016-01-01

Human capital theory was developed to study how individual agents make rational choices or how they invest in human capital to maximize their welfare. One of the leading founders of this perspective, Becker, argues that schooling, on-the-job training, medical care, migration and searching for information about prices and incomes are different…

The management of anxiety, depression and insomnia in the acutely ill medically ill patient.

PubMed

Wise, T N

1994-06-01

Anxiety, depression and insomnia are common conditions among medically ill patients. Such disorders may be reactions to the hospital environment, categorical psychiatric disorders or symptoms of the medical condition. Treatment includes both psychotherapy and rational psychopharmacology that considers both the route of administration and side effects of the agent utilized.

Framework Stabilization of Si-Rich LTA Zeolite Prepared in Organic-Free Media

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

Conato, Marlon T.; Oleksiak, Matthew D.; McGrail, B. Peter

2014-10-16

Zeolite HOU-2 (LTA type) is prepared with the highest silica content (Si/Al = 2.1) reported for Na-LTA zeolites without the use of an organic structure-directing agent. The rational design of Si-rich zeolites has the potential to improve their thermal stability for applications in catalysis, gas storage, and selective separations.

Protein immobilization onto various surfaces using a polymer-bound isocyanate

NASA Astrophysics Data System (ADS)

Kang, Hyun-Jin; Cha, Eun Ji; Park, Hee-Deung

2015-01-01

Silane coupling agents have been widely used for immobilizing proteins onto inorganic surfaces. However, the immobilization method using silane coupling agents requires several treatment steps, and its application is limited to only surfaces containing hydroxyl groups. The aim of this study was to develop a novel method to overcome the limitations of the silane-based immobilization method using a polymer-bound isocyanate. Initially, polymer-bound isocyanate was dissolved in organic solvent and then was used to dip-coat inorganic surfaces. Proteins were then immobilized onto the dip-coated surfaces by the formation of urea bonds between the isocyanate groups of the polymer and the amine groups of the protein. The reaction was verified by FT-IR in which NCO stretching peaks disappeared, and CO and NH stretching peaks appeared after immobilization. The immobilization efficiency of the newly developed method was insensitive to reaction temperatures (4-50 °C), but the efficiency increased with reaction time and reached a maximum after 4 h. Furthermore, the method showed comparable immobilization efficiency to the silane-based immobilization method and was applicable to surfaces that cannot form hydroxyl groups. Taken together, the newly developed method provides a simple and efficient platform for immobilizing proteins onto surfaces.

X-ray structures define human P2X(3) receptor gating cycle and antagonist action.

PubMed

Mansoor, Steven E; Lü, Wei; Oosterheert, Wout; Shekhar, Mrinal; Tajkhorshid, Emad; Gouaux, Eric

2016-10-06

P2X receptors are trimeric, non-selective cation channels activated by ATP that have important roles in the cardiovascular, neuronal and immune systems. Despite their central function in human physiology and although they are potential targets of therapeutic agents, there are no structures of human P2X receptors. The mechanisms of receptor desensitization and ion permeation, principles of antagonism, and complete structures of the pore-forming transmembrane domains of these receptors remain unclear. Here we report X-ray crystal structures of the human P2X 3 receptor in apo/resting, agonist-bound/open-pore, agonist-bound/closed-pore/desensitized and antagonist-bound/closed states. The open state structure harbours an intracellular motif we term the 'cytoplasmic cap', which stabilizes the open state of the ion channel pore and creates lateral, phospholipid-lined cytoplasmic fenestrations for water and ion egress. The competitive antagonists TNP-ATP and A-317491 stabilize the apo/resting state and reveal the interactions responsible for competitive inhibition. These structures illuminate the conformational rearrangements that underlie P2X receptor gating and provide a foundation for the development of new pharmacological agents.

Leveraging structure determination with fragment screening for infectious disease drug targets: MECP synthase from Burkholderia pseudomallei

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

Begley, Darren W.; Hartley, Robert C.; Davies, Douglas R.

As part of the Seattle Structural Genomics Center for Infectious Disease, we seek to enhance structural genomics with ligand-bound structure data which can serve as a blueprint for structure-based drug design. We have adapted fragment-based screening methods to our structural genomics pipeline to generate multiple ligand-bound structures of high priority drug targets from pathogenic organisms. In this study, we report fragment screening methods and structure determination results for 2C-methyl-D-erythritol-2,4-cyclo-diphosphate (MECP) synthase from Burkholderia pseudomallei, the gram-negative bacterium which causes melioidosis. Screening by nuclear magnetic resonance spectroscopy as well as crystal soaking followed by X-ray diffraction led to the identification ofmore » several small molecules which bind this enzyme in a critical metabolic pathway. A series of complex structures obtained with screening hits reveal distinct binding pockets and a range of small molecules which form complexes with the target. Additional soaks with these compounds further demonstrate a subset of fragments to only bind the protein when present in specific combinations. This ensemble of fragment-bound complexes illuminates several characteristics of MECP synthase, including a previously unknown binding surface external to the catalytic active site. These ligand-bound structures now serve to guide medicinal chemists and structural biologists in rational design of novel inhibitors for this enzyme.« less

Modeling ligand recognition at the P2Y12 receptor in light of X-ray structural information

NASA Astrophysics Data System (ADS)

Paoletta, Silvia; Sabbadin, Davide; von Kügelgen, Ivar; Hinz, Sonja; Katritch, Vsevolod; Hoffmann, Kristina; Abdelrahman, Aliaa; Straßburger, Jens; Baqi, Younis; Zhao, Qiang; Stevens, Raymond C.; Moro, Stefano; Müller, Christa E.; Jacobson, Kenneth A.

2015-08-01

The G protein-coupled P2Y12 receptor (P2Y12R) is an important antithrombotic target and of great interest for pharmaceutical discovery. Its recently solved, highly divergent crystallographic structures in complex either with nucleotides (full or partial agonist) or with a nonnucleotide antagonist raise the question of which structure is more useful to understand ligand recognition. Therefore, we performed extensive molecular modeling studies based on these structures and mutagenesis, to predict the binding modes of major classes of P2Y12R ligands previously reported. Various nucleotide derivatives docked readily to the agonist-bound P2Y12R, but uncharged nucleotide-like antagonist ticagrelor required a hybrid receptor resembling the agonist-bound P2Y12R except for the top portion of TM6. Supervised molecular dynamics (SuMD) of ticagrelor binding indicated interactions with the extracellular regions of P2Y12R, defining possible meta-binding sites. Ureas, sulfonylureas, sulfonamides, anthraquinones and glutamic acid piperazines docked readily to the antagonist-bound P2Y12R. Docking dinucleotides at both agonist- and antagonist-bound structures suggested interactions with two P2Y12R pockets. Thus, our structure-based approach consistently rationalized the main structure-activity relationships within each ligand class, giving useful information for designing improved ligands.

The role of oxidative stress in organophosphate and nerve agent toxicity

PubMed Central

Pearson, Jennifer N.; Patel, Manisha

2016-01-01

Organophosphate nerve agents exert their toxicity through inhibition of acetylcholinesterase. The excessive stimulation of cholinergic receptors rapidly causes neuronal damage, seizures, death, and long-term neurological impairment in those that survive. Owing to the lethality of organophosphorus agents and the growing risk they pose, medical interventions that prevent organophosphate toxicity and the delayed injury response are much needed. Studies have shown that oxidative stress occurs in models of subacute, acute, and chronic exposure to organophosphate agents. Key findings of these studies include alterations in mitochondrial function and increased free radical–mediated injury, such as lipid peroxidation. This review focuses on the role of reactive oxygen species in organophosphate neurotoxicity and its dependence on seizure activity. Understanding the sources, mechanisms, and pathological consequences of organophosphate-induced oxidative stress can lead to the development of rational therapies for treating toxic exposures. PMID:27371936

The Analgesic Potential of Cannabinoids

PubMed Central

Elikottil, Jaseena; Gupta, Pankaj; Gupta, Kalpna

2013-01-01

Historically and anecdotally cannabinoids have been used as analgesic agents. In recent years, there has been an escalating interest in developing cannabis-derived medications to treat severe pain. This review provides an overview of the history of cannabis use in medicine, cannabinoid signaling pathways, and current data from preclinical as well as clinical studies on using cannabinoids as potential analgesic agents. Clinical and experimental studies show that cannabis-derived compounds act as anti-emetic, appetite modulating and analgesic agents. However, the efficacy of individual products is variable and dependent upon the route of administration. Since opioids are the only therapy for severe pain, analgesic ability of cannabinoids may provide a much-needed alternative to opioids. Moreover, cannabinoids act synergistically with opioids and act as opioid sparing agents, allowing lower doses and fewer side effects from chronic opioid therapy. Thus, rational use of cannabis based medications deserves serious consideration to alleviate the suffering of patients due to severe pain. PMID:20073408

New antithrombotic agents in the ambulatory setting.

PubMed

Gibbs, Neville M; Weightman, William M; Watts, Stephen A

2014-12-01

Many patients presenting for surgical or other procedures in an ambulatory setting are taking new antiplatelet or anticoagulant agents. This review assesses how the novel features of these new agents affect the management of antithrombotic therapy in the ambulatory setting. There have been very few studies investigating the relative risks of continuing or ceasing new antithrombotic agents. Recent reviews indicate that the new antithrombotic agents offer greater efficacy or ease of administration but are more difficult to monitor or reverse. They emphasize the importance of assessing the bleeding risk of the procedure, the thrombotic risk if the agent is ceased, and patient factors that increase the likelihood of bleeding. The timing of cessation of the agent, if required, depends on its pharmacokinetics and patients' bleeding risks. Patients at high risk of thrombotic complications may require bridging therapy. Once agreed upon, the perioperative plan should be made clear to all involved. As there are few clinical studies to guide management, clinicians must make rational decisions in relation to continuing or ceasing new antithrombotic agents. This requires knowledge of their pharmacokinetics, and a careful multidisciplinary assessment of the relative thrombotic and bleeding risks in individual patients.

Highly stabilized gadolinium chelates functionalized on metal nanoparticles as magnetic resonance imaging contrast agent

NASA Astrophysics Data System (ADS)

Siddiqui, Talha S.

Magnetic resonance imaging (MRI) is a non-invasive method for imaging and diagnosing tissue damage, organ function and the vascular system. Magnevist(TM) a complex of diethylenetriaminepentaacetic acid (DTPA) and Gd3+ is a clinically approved contrast agent for MRI. A derivative of DTPA was formed by the addition of two cysteine groups (DTPA-L-Cys) through amide linkage. The Gd complex of this ligand bonds with the silver surfaces through the cysteine thiols. GdDTPA-L-Cys was bound to ˜10nm diameter Ag nanoparticles for use as a multifunctional MRI contrast agent. The ligand and complex were characterized by 1H and 13C NMR, ESI-MS and IR spectroscopy. The silver construct was characterized by TEM, TGA and UV-Vis absorption spectra. The per metal complex r1 relaxivity of GdDTPA-L-Cys{Ag} greater than that of Magnavist(TM) with the same molarity for both compounds. The synthesis of a DTPA derivative is described that allows it to bind to silver or gold nanoparticles through a single thiol linkage (DTPASH). The resulting Gd complex, GdDTPASH, was bound to Ag nanoparticles to create a single monolayer on the surface. The construct was further stabilized in buffered solution with the addition of a thiolated PEG chain. The highly stabilized nanoparticle construct delivers a high payload of Gd compelex and is an effective T1 brightening agent. The production of this type of construct opens the way for engineered multimodal MRI contrast agents.

Model reduction for agent-based social simulation: coarse-graining a civil violence model.

PubMed

Zou, Yu; Fonoberov, Vladimir A; Fonoberova, Maria; Mezic, Igor; Kevrekidis, Ioannis G

2012-06-01

Agent-based modeling (ABM) constitutes a powerful computational tool for the exploration of phenomena involving emergent dynamic behavior in the social sciences. This paper demonstrates a computer-assisted approach that bridges the significant gap between the single-agent microscopic level and the macroscopic (coarse-grained population) level, where fundamental questions must be rationally answered and policies guiding the emergent dynamics devised. Our approach will be illustrated through an agent-based model of civil violence. This spatiotemporally varying ABM incorporates interactions between a heterogeneous population of citizens [active (insurgent), inactive, or jailed] and a population of police officers. Detailed simulations exhibit an equilibrium punctuated by periods of social upheavals. We show how to effectively reduce the agent-based dynamics to a stochastic model with only two coarse-grained degrees of freedom: the number of jailed citizens and the number of active ones. The coarse-grained model captures the ABM dynamics while drastically reducing the computation time (by a factor of approximately 20).

Model reduction for agent-based social simulation: Coarse-graining a civil violence model

NASA Astrophysics Data System (ADS)

Zou, Yu; Fonoberov, Vladimir A.; Fonoberova, Maria; Mezic, Igor; Kevrekidis, Ioannis G.

2012-06-01

Agent-based modeling (ABM) constitutes a powerful computational tool for the exploration of phenomena involving emergent dynamic behavior in the social sciences. This paper demonstrates a computer-assisted approach that bridges the significant gap between the single-agent microscopic level and the macroscopic (coarse-grained population) level, where fundamental questions must be rationally answered and policies guiding the emergent dynamics devised. Our approach will be illustrated through an agent-based model of civil violence. This spatiotemporally varying ABM incorporates interactions between a heterogeneous population of citizens [active (insurgent), inactive, or jailed] and a population of police officers. Detailed simulations exhibit an equilibrium punctuated by periods of social upheavals. We show how to effectively reduce the agent-based dynamics to a stochastic model with only two coarse-grained degrees of freedom: the number of jailed citizens and the number of active ones. The coarse-grained model captures the ABM dynamics while drastically reducing the computation time (by a factor of approximately 20).

Current and emerging treatment options in the management of lupus

PubMed Central

Jordan, Natasha; D’Cruz, David

2016-01-01

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with variable clinical manifestations. While the clearest guidelines for the treatment of SLE exist in the context of lupus nephritis, patients with other lupus manifestations such as neuropsychiatric, hematologic, musculoskeletal, and severe cutaneous lupus frequently require immunosuppression and/or biologic therapy. Conventional immunosuppressive agents such as mycophenolate mofetil, azathioprine, and cyclophosphamide are widely used in the management of SLE with current more rationalized treatment regimens optimizing the use of these agents while minimizing potential toxicity. The advent of biologic therapies has advanced the treatment of SLE particularly in patients with refractory disease. The CD20 monoclonal antibody rituximab and the anti-BLyS agent belimumab are now widely in use in clinical practice. Several other biologic agents are in ongoing clinical trials. While immunosuppressive and biologic agents are the foundation of inflammatory disease control in SLE, the importance of managing comorbidities such as cardiovascular risk factors, bone health, and minimizing susceptibility to infection should not be neglected. PMID:27529058

A new class of finite-time nonlinear consensus protocols for multi-agent systems

NASA Astrophysics Data System (ADS)

Zuo, Zongyu; Tie, Lin

2014-02-01

This paper is devoted to investigating the finite-time consensus problem for a multi-agent system in networks with undirected topology. A new class of global continuous time-invariant consensus protocols is constructed for each single-integrator agent dynamics with the aid of Lyapunov functions. In particular, it is shown that the settling time of the proposed new class of finite-time consensus protocols is upper bounded for arbitrary initial conditions. This makes it possible for network consensus problems that the convergence time is designed and estimated offline for a given undirected information flow and a group volume of agents. Finally, a numerical simulation example is presented as a proof of concept.

Distributed robust finite-time nonlinear consensus protocols for multi-agent systems

NASA Astrophysics Data System (ADS)

Zuo, Zongyu; Tie, Lin

2016-04-01

This paper investigates the robust finite-time consensus problem of multi-agent systems in networks with undirected topology. Global nonlinear consensus protocols augmented with a variable structure are constructed with the aid of Lyapunov functions for each single-integrator agent dynamics in the presence of external disturbances. In particular, it is shown that the finite settling time of the proposed general framework for robust consensus design is upper bounded for any initial condition. This makes it possible for network consensus problems to design and estimate the convergence time offline for a multi-agent team with a given undirected information flow. Finally, simulation results are presented to demonstrate the performance and effectiveness of our finite-time protocols.

Adsorbate-mediated strong metal–support interactions in oxide-supported Rh catalysts

DOE PAGES

Matsubu, John C.; Zhang, Shuyi; DeRita, Leo; ...

2016-09-19

The optimization of supported metal catalysts predominantly focuses on engineering the metal site, for which physical insights based on extensive theoretical and experimental contributions have enabled the rational design of active sites. Although it is well known that supports can influence the catalytic properties of metals, insights into how metal–support interactions can be exploited to optimize metal active-site properties are lacking. Here in this paper, we utilize in situ spectroscopy and microscopy to identify and characterize a support effect in oxide-supported heterogeneous Rh catalysts. This effect is characterized by strongly bound adsorbates (HCO x) on reducible oxide supports (TiO 2more » and Nb 2O 5) that induce oxygen-vacancy formation in the support and cause HCO x-functionalized encapsulation of Rh nanoparticles by the support. The encapsulation layer is permeable to reactants, stable under the reaction conditions and strongly influences the catalytic properties of Rh, which enables rational and dynamic tuning of CO 2-reduction selectivity.« less

Structure of the Escherichia coli phosphonate binding protein PhnD and rationally optimized phosphonate biosensors.

PubMed

Alicea, Ismael; Marvin, Jonathan S; Miklos, Aleksandr E; Ellington, Andrew D; Looger, Loren L; Schreiter, Eric R

2011-12-02

The phnD gene of Escherichia coli encodes the periplasmic binding protein of the phosphonate (Pn) uptake and utilization pathway. We have crystallized and determined structures of E. coli PhnD (EcPhnD) in the absence of ligand and in complex with the environmentally abundant 2-aminoethylphosphonate (2AEP). Similar to other bacterial periplasmic binding proteins, 2AEP binds near the center of mass of EcPhnD in a cleft formed between two lobes. Comparison of the open, unliganded structure with the closed 2AEP-bound structure shows that the two lobes pivot around a hinge by ~70° between the two states. Extensive hydrogen bonding and electrostatic interactions stabilize 2AEP, which binds to EcPhnD with low nanomolar affinity. These structures provide insight into Pn uptake by bacteria and facilitated the rational design of high signal-to-noise Pn biosensors based on both coupled small-molecule dyes and autocatalytic fluorescent proteins. Copyright © 2011 Elsevier Ltd. All rights reserved.

Structure of the Escherichia coli Phosphonate Binding Protein PhnD and Rationally Optimized Phosphonate Biosensors

PubMed Central

Alicea, Ismael; Marvin, Jonathan S.; Miklos, Aleksandr E.; Ellington, Andrew D.; Looger, Loren L.; Schreiter, Eric R.

2012-01-01

The phnD gene of Escherichia coli encodes the periplasmic binding protein of the phosphonate uptake and utilization pathway. We have crystallized and determined structures of E. coli PhnD (EcPhnD) in the absence of ligand and in complex with the environmentally abundant 2-aminoethylphosphonate (2AEP). Similar to other bacterial periplasmic binding proteins, 2AEP binds near the center of mass of EcPhnD in a cleft formed between two lobes. Comparison of the open, unliganded structure with the closed 2AEP-bound structure shows that the two lobes pivot around a hinge by ~70° between the two states. Extensive hydrogen bonding and electrostatic interactions stabilize 2AEP, which binds to EcPhnD with low nanomolar affinity. These structures provide insight into phosphonate uptake by bacteria and facilitated the rational design of high signal-to-noise phosphonate biosensors based both on coupled small molecule dyes and autocatalytic fluorescent proteins. PMID:22019591

Attention and choice: a review on eye movements in decision making.

PubMed

Orquin, Jacob L; Mueller Loose, Simone

2013-09-01

This paper reviews studies on eye movements in decision making, and compares their observations to theoretical predictions concerning the role of attention in decision making. Four decision theories are examined: rational models, bounded rationality, evidence accumulation, and parallel constraint satisfaction models. Although most theories were confirmed with regard to certain predictions, none of the theories adequately accounted for the role of attention during decision making. Several observations emerged concerning the drivers and down-stream effects of attention on choice, suggesting that attention processes plays an active role in constructing decisions. So far, decision theories have largely ignored the constructive role of attention by assuming that it is entirely determined by heuristics, or that it consists of stochastic information sampling. The empirical observations reveal that these assumptions are implausible, and that more accurate assumptions could have been made based on prior attention and eye movement research. Future decision making research would benefit from greater integration with attention research. Copyright © 2013 Elsevier B.V. All rights reserved.

Structure of the Escherichia coli Phosphonate Binding Protein PhnD and Rationally Optimized Phosphonate Biosensors

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

Alicea, Ismael; Marvin, Jonathan S.; Miklos, Aleksandr E.

2012-09-17

The phnD gene of Escherichia coli encodes the periplasmic binding protein of the phosphonate (Pn) uptake and utilization pathway. We have crystallized and determined structures of E. coli PhnD (EcPhnD) in the absence of ligand and in complex with the environmentally abundant 2-aminoethylphosphonate (2AEP). Similar to other bacterial periplasmic binding proteins, 2AEP binds near the center of mass of EcPhnD in a cleft formed between two lobes. Comparison of the open, unliganded structure with the closed 2AEP-bound structure shows that the two lobes pivot around a hinge by {approx}70{sup o} between the two states. Extensive hydrogen bonding and electrostatic interactionsmore » stabilize 2AEP, which binds to EcPhnD with low nanomolar affinity. These structures provide insight into Pn uptake by bacteria and facilitated the rational design of high signal-to-noise Pn biosensors based on both coupled small-molecule dyes and autocatalytic fluorescent proteins.« less

Therapeutic efficacy of ferrofluid bound anticancer agent

NASA Astrophysics Data System (ADS)

Alexiou, Ch.; Arnold, W.; Hulin, P.; Klein, R.; Schmidt, A.; Bergemannand, Ch.; Parak, F. G.

2001-09-01

Ferrofluids coated with starch polymers can be used as biocompatible carriers in a new field of locoregional tumor therapy called "magnetic drug targeting". Bound to medical drugs, such magnetic nanoparticles can be enriched in a desired body compartment using an external magnetic field. In the present study, we confirm the concentration of ferrofluids in VX2 squamous cell carcinoma tissue of the rabbit using histological investigations and MR imaging. The therapeutic efficacy of "magnetic drug targeting" was studied using the rabbit VX2 squamous cell carcinoma model. Mitoxantrone coupled ferrofluids were injected intraarterially into the artery supplying the tumor (femoral artery). The magnetic field (1.7 Tesla) was focused to the tumor placed at the medial portion of the hind limb of New Zealand White rabbits. Complete tumor remissions could be seen without any negative side effects by using only 20% of the normal systemic dosage of the chemotherapeutic agent mitoxantrone. Figs 3, Refs 14.

Swarming behaviors in multi-agent systems with nonlinear dynamics

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

Yu, Wenwu, E-mail: wenwuyu@gmail.com; School of Electrical and Computer Engineering, RMIT University, Melbourne VIC 3001; Chen, Guanrong

2013-12-15

The dynamic analysis of a continuous-time multi-agent swarm model with nonlinear profiles is investigated in this paper. It is shown that, under mild conditions, all agents in a swarm can reach cohesion within a finite time, where the upper bounds of the cohesion are derived in terms of the parameters of the swarm model. The results are then generalized by considering stochastic noise and switching between nonlinear profiles. Furthermore, swarm models with limited sensing range inducing changing communication topologies and unbounded repulsive interactions between agents are studied by switching system and nonsmooth analysis. Here, the sensing range of each agentmore » is limited and the possibility of collision among nearby agents is high. Finally, simulation results are presented to demonstrate the validity of the theoretical analysis.« less

Rational drug design for anti-cancer chemotherapy: multi-target QSAR models for the in silico discovery of anti-colorectal cancer agents.

PubMed

Speck-Planche, Alejandro; Kleandrova, Valeria V; Luan, Feng; Cordeiro, M Natália D S

2012-08-01

The discovery of new and more potent anti-cancer agents constitutes one of the most active fields of research in chemotherapy. Colorectal cancer (CRC) is one of the most studied cancers because of its high prevalence and number of deaths. In the current pharmaceutical design of more efficient anti-CRC drugs, the use of methodologies based on Chemoinformatics has played a decisive role, including Quantitative-Structure-Activity Relationship (QSAR) techniques. However, until now, there is no methodology able to predict anti-CRC activity of compounds against more than one CRC cell line, which should constitute the principal goal. In an attempt to overcome this problem we develop here the first multi-target (mt) approach for the virtual screening and rational in silico discovery of anti-CRC agents against ten cell lines. Here, two mt-QSAR classification models were constructed using a large and heterogeneous database of compounds. The first model was based on linear discriminant analysis (mt-QSAR-LDA) employing fragment-based descriptors while the second model was obtained using artificial neural networks (mt-QSAR-ANN) with global 2D descriptors. Both models correctly classified more than 90% of active and inactive compounds in training and prediction sets. Some fragments were extracted from the molecules and their contributions to anti-CRC activity were calculated using mt-QSAR-LDA model. Several fragments were identified as potential substructural features responsible for the anti-CRC activity and new molecules designed from those fragments with positive contributions were suggested and correctly predicted by the two models as possible potent and versatile anti-CRC agents. Copyright © 2012 Elsevier Ltd. All rights reserved.

Strategic Aspects of Communication

NASA Astrophysics Data System (ADS)

Hagen, Edward; Hammerstein, Peter; Hess, Nicole

Rarely do human behavioral scientists and scholars study language, music, and other forms of communication as strategies—a means to some end. Some even deny that communication is the primary function of these phenomena. Here we draw upon selections of our earlier work to briefly define the strategy concept and sketch how decision theory, developed to explain the behavior of rational actors, is applied to evolved agents. Communication can then be interpreted as a strategy that advances the "fitness interests" of such agents. When this perspective is applied to agents with conflicts of interest, deception emerges as an important aspect of communication. We briefly review costly signaling, one solution to the problem of honest communication among agents with conflicts of interest. We also explore the subversion of cooperative signals by parasites and by plants defending themselves against herbivores, and we touch on biases in human gossip. Experiments with artificial embodied and communicating agents confirm that when there are conflicts of interest among agents, deception readily evolves. Finally, we consider signaling among super-organisms and the possible implications for understanding human music and language.

Processing yields and meat flavor of broilers fed a mixture of narasin and nicarbazin as an anticoccidial agent.

PubMed

Peng, I C; Larsen, J E; Stadelman, W J; Jones, D J; Tonkinson, L V

1987-08-01

Processed yields (percent hot carcass) and cooked meat flavor of broilers fed 100 ppm of an anticoccidial agent (a mixture of 50 ppm narasin and 50 ppm nicarbazin) were compared with yields of birds fed a ration without the anticoccidial agent. Broilers were processed at 7 wk of age (49 days) after a 4-day withdrawal from the anticoccidial agent for the treated birds. The flavor of meat was evaluated by a 12-member sensory panel. Meat was either deep fat-fried or oven roasted. Sensory evaluations were made on freshly cooked samples and on cooked meat refrigerated for 24 h and reheated. The anticoccidial agent did not produce a difference (P greater than .05) in the hot carcass yields of the broilers as compared with control birds fed the nonmedicated diet. Analyses of triangle test data for flavor evaluations by two statistical methods indicated that there were no detectable differences (P greater than .05) in flavor between broilers fed the anticoccidial agent in the diet and those fed the control diet.

The problem with rescue medicine.

PubMed

Jecker, Nancy S

2013-02-01

Is there a rational and ethical basis for efforts to rescue individuals in dire straits? When does rescue have ethical support, and when does it reflect an irrational impulse? This paper defines a Rule of Rescue and shows its intuitive appeal. It then proceeds to argue that this rule lacks support from standard principles of justice and from ethical principles more broadly, and should be rejected in many situations. I distinguish between agent-relative and agent-neutral reasons, and argue that the Rule of Rescue qualifies only in a narrow range of cases where agent-relative considerations apply. I conclude that it would be wise to set aside the Rule of Rescue in many cases, especially those involving public policies, where it has only weak normative justification. The broader implications of this analysis are noted.

The rational design of recognitive polymeric networks for sensing applications

NASA Astrophysics Data System (ADS)

Noss, Kimberly Ryanne Dial

Testosterone recognitive networks were synthesized with varying feed crosslinking percentages and length of the bi-functional crosslinking agent to analyze the effect of changing structural parameters on template binding properties such as affinity, selectivity, capacity, and diffusional transport. The crosslinking percentage of the crosslinking monomer ethylene glycol dimethacrylate was varied from 50% to 90% and associated networks experienced a 2 fold increase in capacity and a 4 fold increase in affinity with the equilibrium association constants, Ka, ranging from 0.32 +/- 0.02 x 10 4 M-1 to 1.3 +/- 0.1 x 104 M -1, respectively. The higher concentration of crosslinking monomer increased the crosslinking points available for inter-chain stabilization creating an increased number of stable cavities for template association. However, by increasing the length of the crosslinking agent and increasing the feed crosslinking percentage from 77% crosslinked poly(methacrylic acid- co-ethylene glycol dimethacrylate) (poly(MAA-co-EGDMA)) to 50% crosslinked poly(methacrylic acid-co-poly(ethylene glycol)200 dimethacrylate) (poly(MAA-co-PEG200DMA)), the mesh size of the network increased resulting in an increased template diffusion coefficient from (2.83 +/- 0.06) x 109 cm2/s to (4.3 +/- 0.06) x 109 cm2/s, respectively, which is approximately a 40% faster template diffussional transport. A 77% crosslinked poly (MAA-co-PEG200DMA) recognitive network had an association constant of (0.20 +/- 0.05) x 104 M -1 and bound (0.72 +/- 0.04) x 10-2 mmol testosterone/g dry polymer, which was less by 6 and 3 fold, respectively, compared to a similarly crosslinked poly(MAA-co-EGDMA) recognitive network. Structural manipulation of the macromolecular architecture illustrates the programmability of recognitive networks for specific template binding parameters and diffusional transport, which may lead to enhanced imprinted sensor materials and successful integration onto sensor platforms.

Maximization, learning, and economic behavior

PubMed Central

Erev, Ido; Roth, Alvin E.

2014-01-01

The rationality assumption that underlies mainstream economic theory has proved to be a useful approximation, despite the fact that systematic violations to its predictions can be found. That is, the assumption of rational behavior is useful in understanding the ways in which many successful economic institutions function, although it is also true that actual human behavior falls systematically short of perfect rationality. We consider a possible explanation of this apparent inconsistency, suggesting that mechanisms that rest on the rationality assumption are likely to be successful when they create an environment in which the behavior they try to facilitate leads to the best payoff for all agents on average, and most of the time. Review of basic learning research suggests that, under these conditions, people quickly learn to maximize expected return. This review also shows that there are many situations in which experience does not increase maximization. In many cases, experience leads people to underweight rare events. In addition, the current paper suggests that it is convenient to distinguish between two behavioral approaches to improve economic analyses. The first, and more conventional approach among behavioral economists and psychologists interested in judgment and decision making, highlights violations of the rational model and proposes descriptive models that capture these violations. The second approach studies human learning to clarify the conditions under which people quickly learn to maximize expected return. The current review highlights one set of conditions of this type and shows how the understanding of these conditions can facilitate market design. PMID:25024182

Maximization, learning, and economic behavior.

PubMed

Erev, Ido; Roth, Alvin E

2014-07-22

The rationality assumption that underlies mainstream economic theory has proved to be a useful approximation, despite the fact that systematic violations to its predictions can be found. That is, the assumption of rational behavior is useful in understanding the ways in which many successful economic institutions function, although it is also true that actual human behavior falls systematically short of perfect rationality. We consider a possible explanation of this apparent inconsistency, suggesting that mechanisms that rest on the rationality assumption are likely to be successful when they create an environment in which the behavior they try to facilitate leads to the best payoff for all agents on average, and most of the time. Review of basic learning research suggests that, under these conditions, people quickly learn to maximize expected return. This review also shows that there are many situations in which experience does not increase maximization. In many cases, experience leads people to underweight rare events. In addition, the current paper suggests that it is convenient to distinguish between two behavioral approaches to improve economic analyses. The first, and more conventional approach among behavioral economists and psychologists interested in judgment and decision making, highlights violations of the rational model and proposes descriptive models that capture these violations. The second approach studies human learning to clarify the conditions under which people quickly learn to maximize expected return. The current review highlights one set of conditions of this type and shows how the understanding of these conditions can facilitate market design.

Exploring the Influence of Smallholders' Perceptions Regarding Water Availability on Crop Choice and Water Allocation Through Socio-Hydrological Modeling

NASA Astrophysics Data System (ADS)

Kuil, L.; Evans, T.; McCord, P. F.; Salinas, J. L.; Blöschl, G.

2018-04-01

While it is known that farmers adopt different decision-making behaviors to cope with stresses, it remains challenging to capture this diversity in formal model frameworks that are used to advance theory and inform policy. Guided by cognitive theory and the theory of bounded rationality, this research develops a novel, socio-hydrological model framework that can explore how a farmer's perception of water availability impacts crop choice and water allocation. The model is informed by a rich empirical data set at the household level collected during 2013 in Kenya's Upper Ewaso Ng'iro basin that shows that the crop type cultivated is correlated with water availability. The model is able to simulate this pattern and shows that near-optimal or "satisficing" crop patterns can emerge also when farmers were to make use of simple decision rules and have diverse perceptions on water availability. By focusing on farmer decision making it also captures the rebound effect, i.e., as additional water becomes available through the improvement of crop efficiencies it will be reallocated on the farm instead of flowing downstream, as a farmer will adjust his (her) water allocation and crop pattern to the new water conditions. This study is valuable as it is consistent with the theory of bounded rationality, and thus offers an alternative, descriptive model in addition to normative models. The framework can be used to understand the potential impact of climate change on the socio-hydrological system, to simulate and test various assumptions regarding farmer behavior and to evaluate policy interventions.

The Teacher from the Black Lagoon: Revenge of the "Bad Teacher"

ERIC Educational Resources Information Center

Beck, Bernard

2012-01-01

School teachers have been used as heroic characters in movies for a long time. Their heroism compensates for the failures of social life in our society by treating problems in the classroom, not the real world, and by acting as the mediators between diverse sub-cultures and the larger society. They are the agents of rationality, scholarship, and…

SURVIVABILITY THROUGH OPTIMIZING RESILIENT MECHANISMS (STORM)

DTIC Science & Technology

2017-04-01

STATEMENT Approved for Public Release; Distribution Unlimited. PA# 88ABW-2017-0894 Date Cleared: 07 Mar 2017 13. SUPPLEMENTARY NOTES 14. ABSTRACT Game ...quantitatively about cyber-attacks. Game theory is the branch of applied mathematics that formalizes strategic interaction among intelligent rational agents...mechanism based on game theory. This work has applied game theory to numerous cyber security problems: cloud security, cyber threat information sharing

If It Ain't Survival...It's Catastrophe: A Social Studies Curriculum for a Modern World.

ERIC Educational Resources Information Center

Knox, Gary A.

The goal of the Marin Social Studies Project was to present a relevant and comprehensive design for American social studies education and to serve as a change agent by providing rational and viable alternatives to present practices. This paper documents the development of this curriculum design, defining the purpose of teaching and the nature of…

PARP inhibition: PARP1 and beyond

PubMed Central

Rouleau, Michèle; Patel, Anand; Hendzel, Michael J.; Kaufmann, Scott H.; Poirier, Guy G.

2010-01-01

Recent findings have thrust poly(ADP-ribose) polymerases (PARPs) into the limelight as potential chemotherapeutic targets. To provide a framework for understanding these recent observations, we review what is known about the structures and functions of the family of PARP enzymes, and then outline a series of questions that should be addressed to guide the rational development of PARP inhibitors as anticancer agents. PMID:20200537

L-DOPA-Coated Manganese Oxide Nanoparticles as Dual MRI Contrast Agents and Drug-Delivery Vehicles.

PubMed

McDonagh, Birgitte Hjelmeland; Singh, Gurvinder; Hak, Sjoerd; Bandyopadhyay, Sulalit; Augestad, Ingrid Lovise; Peddis, Davide; Sandvig, Ioanna; Sandvig, Axel; Glomm, Wilhelm Robert

2016-01-20

Manganese oxide nanoparticles (MONPs) are capable of time-dependent magnetic resonance imaging contrast switching as well as releasing a surface-bound drug. MONPs give T2/T2* contrast, but dissolve and release T1-active Mn(2+) and L-3,4-dihydroxyphenylalanine. Complementary images are acquired with a single contrast agent, and applications toward Parkinson's disease are suggested. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Transport modalities of photodynamic agents for tumors

NASA Astrophysics Data System (ADS)

Reddi, Elena

1994-03-01

Systemically injected porphyrins and other tetrapyrrolic compounds associate with serum proteins. Highly hydrophobic photosensitizers are mainly associated with lipoproteins and are deposited in intracellular loci of the neoplastic tissue. Hydrophilic photosensitizers are preferentially bound by serum albumin that releases the dye in the vascular stroma of the tumor. As a consequence the type of photosensitizer carrier determines different mechanisms of PDT-induced tumor necrosis. Low-density lipoproteins (LDL) may increase the selectivity of tumor targeting by releasing the bound dye to the neoplastic cells by a receptor-mediated endocytotic mechanism.

Cd(2+) Triggered the FRET "ON": A New Molecular Switch for the Ratiometric Detection of Cd(2+) with Live-Cell Imaging and Bound X-ray Structure.

PubMed

Aich, Krishnendu; Goswami, Shyamaprosad; Das, Sangita; Mukhopadhyay, Chitrangada Das; Quah, Ching Kheng; Fun, Hoong-Kun

2015-08-03

On the basis of the Förster resonance energy transfer mechanism between rhodamine and quinoline-benzothiazole conjugated dyad, a new colorimetric as well as fluorescence ratiometric probe was synthesized for the selective detection of Cd(2+). The complex formation of the probe with Cd(2+) was confirmed through Cd(2+)-bound single-crystal structure. Capability of the probe as imaging agent to detect the cellular uptake of Cd(2+) was demonstrated here using living RAW cells.

Dancing partners at the ball: Rational selection of next generation anti-CD20 antibodies for combination therapy of chronic lymphocytic leukemia in the novel agents era.

PubMed

Butler, L A; Tam, C S; Seymour, J F

2017-09-01

The anti-CD20 antibodies represent a major advancement in the therapeutic options available for chronic lymphocytic leukemia. The addition of rituximab, ofatumumab and obinutuzumab to various chemotherapy regimens has led to considerable improvements in both response and survival. Ocaratuzumab, veltuzumab and ublituximab are currently being explored within the trial setting. We review the current status of these antibodies, and discuss how their mechanisms of action may impact on the choice of combinations with novel small molecule agents. Copyright © 2017 Elsevier Ltd. All rights reserved.

Modeling the Structural Dynamic of Industrial Networks

NASA Astrophysics Data System (ADS)

Wilkinson, Ian F.; Wiley, James B.; Lin, Aizhong

Market systems consist of locally interacting agents who continuously pursue advantageous opportunities. Since the time of Adam Smith, a fundamental task of economics has been to understand how market systems develop and to explain their operation. During the intervening years, theory largely has stressed comparative statics analysis. Based on the assumptions of rational, utility or profit-maximizing agents, and negative, diminishing returns) feedback process, traditional economic analysis seeks to describe the, generally) unique state of an economy corresponding to an initial set of assumptions. The analysis is tatic in the sense that it does not describe the process by which an economy might get from one state to another.

Mcl-1 Degradation Is Required for Targeted Therapeutics to Eradicate Colon Cancer Cells.

PubMed

Tong, Jingshan; Wang, Peng; Tan, Shuai; Chen, Dongshi; Nikolovska-Coleska, Zaneta; Zou, Fangdong; Yu, Jian; Zhang, Lin

2017-05-01

The Bcl-2 family protein Mcl-1 is often degraded in cancer cells subjected to effective therapeutic treatment, and defective Mcl-1 degradation has been associated with intrinsic and acquired drug resistance. However, a causal relationship between Mcl-1 degradation and anticancer drug responses has not been directly established, especially in solid tumor cells where Mcl-1 inhibition alone is insufficient to trigger cell death. In this study, we present evidence that Mcl-1 participates directly in determining effective therapeutic responses in colon cancer cells. In this setting, Mcl-1 degradation was induced by a variety of multikinase inhibitor drugs, where it relied upon GSK3β phosphorylation and FBW7-dependent ubiquitination. Specific blockade by genetic knock-in (KI) abolished apoptotic responses and conferred resistance to kinase inhibitors. Mcl-1 -KI also suppressed the antiangiogenic and anti-hypoxic effects of kinase inhibitors in the tumor microenvironment. Interestingly, these same inhibitors also induced the BH3-only Bcl-2 family protein PUMA, which is required for apoptosis. Degradation-resistant Mcl-1 bound and sequestered PUMA from other prosurvival proteins to maintain cell survival, which was abolished by small-molecule Mcl-1 inhibitors. Our findings establish a pivotal role for Mcl-1 degradation in the response of colon cancer cells to targeted therapeutics, and they provide a useful rational platform to develop Mcl-1-targeting agents that can overcome drug resistance. Cancer Res; 77(9); 2512-21. ©2017 AACR . ©2017 American Association for Cancer Research.

Stock market speculation: Spontaneous symmetry breaking of economic valuation

NASA Astrophysics Data System (ADS)

Sornette, Didier

2000-09-01

Firm foundation theory estimates a security's firm fundamental value based on four determinants: expected growth rate, expected dividend payout, the market interest rate and the degree of risk. In contrast, other views of decision-making in the stock market, using alternatives such as human psychology and behavior, bounded rationality, agent-based modeling and evolutionary game theory, expound that speculative and crowd behavior of investors may play a major role in shaping market prices. Here, we propose that the two views refer to two classes of companies connected through a "phase transition". Our theory is based on (1) the identification of the fundamental parity symmetry of prices (p→-p), which results from the relative direction of payment flux compared to commodity flux and (2) the observation that a company's risk-adjusted growth rate discounted by the market interest rate behaves as a control parameter for the observable price. We find a critical value of this control parameter at which a spontaneous symmetry-breaking of prices occurs, leading to a spontaneous valuation in absence of earnings, similarly to the emergence of a spontaneous magnetization in Ising models in absence of a magnetic field. The low growth rate phase is described by the firm foundation theory while the large growth rate phase is the regime of speculation and crowd behavior. In practice, while large "finite-time horizon" effects round off the predicted singularities, our symmetry-breaking speculation theory accounts for the apparent over-pricing and the high volatility of fast growing companies on the stock markets.

Computation of the target state and feedback controls for time optimal consensus in multi-agent systems

NASA Astrophysics Data System (ADS)

Mulla, Ameer K.; Patil, Deepak U.; Chakraborty, Debraj

2018-02-01

N identical agents with bounded inputs aim to reach a common target state (consensus) in the minimum possible time. Algorithms for computing this time-optimal consensus point, the control law to be used by each agent and the time taken for the consensus to occur, are proposed. Two types of multi-agent systems are considered, namely (1) coupled single-integrator agents on a plane and, (2) double-integrator agents on a line. At the initial time instant, each agent is assumed to have access to the state information of all the other agents. An algorithm, using convexity of attainable sets and Helly's theorem, is proposed, to compute the final consensus target state and the minimum time to achieve this consensus. Further, parts of the computation are parallelised amongst the agents such that each agent has to perform computations of O(N2) run time complexity. Finally, local feedback time-optimal control laws are synthesised to drive each agent to the target point in minimum time. During this part of the operation, the controller for each agent uses measurements of only its own states and does not need to communicate with any neighbouring agents.

Distributed containment control of heterogeneous fractional-order multi-agent systems with communication delays

NASA Astrophysics Data System (ADS)

Yang, Hongyong; Han, Fujun; Zhao, Mei; Zhang, Shuning; Yue, Jun

2017-08-01

Because many networked systems can only be characterized with fractional-order dynamics in complex environments, fractional-order calculus has been studied deeply recently. When diverse individual features are shown in different agents of networked systems, heterogeneous fractional-order dynamics will be used to describe the complex systems. Based on the distinguishing properties of agents, heterogeneous fractional-order multi-agent systems (FOMAS) are presented. With the supposition of multiple leader agents in FOMAS, distributed containment control of FOMAS is studied in directed weighted topologies. By applying Laplace transformation and frequency domain theory of the fractional-order operator, an upper bound of delays is obtained to ensure containment consensus of delayed heterogenous FOMAS. Consensus results of delayed FOMAS in this paper can be extended to systems with integer-order models. Finally, numerical examples are used to verify our results.

Mechanistic Studies of Hafnium-Pyridyl Amido-Catalyzed 1-Octene Polymerization and Chain Transfer Using Quench-Labeling Methods.

PubMed

Cueny, Eric S; Johnson, Heather C; Anding, Bernie J; Landis, Clark R

2017-08-30

Chromophore quench-labeling applied to 1-octene polymerization as catalyzed by hafnium-pyridyl amido precursors enables quantification of the amount of active catalyst and observation of the molecular weight distribution (MWD) of Hf-bound polymers via UV-GPC analysis. Comparison of the UV-detected MWD with the MWD of the "bulk" (all polymers, from RI-GPC analysis) provides important mechanistic information. The time evolution of the dual-detection GPC data, concentration of active catalyst, and monomer consumption suggests optimal activation conditions for the Hf pre-catalyst in the presence of the activator [Ph 3 C][B(C 6 F 5 ) 4 ]. The chromophore quench-labeling agents do not react with the chain-transfer agent ZnEt 2 under the reaction conditions. Thus, Hf-bound polymeryls are selectively labeled in the presence of zinc-polymeryls. Quench-labeling studies in the presence of ZnEt 2 reveal that ZnEt 2 does not influence the rate of propagation at the Hf center, and chain transfer of Hf-bound polymers to ZnEt 2 is fast and quasi-irreversible. The quench-label techniques represent a means to study commercial polymerization catalysts that operate with high efficiency at low catalyst concentrations without the need for specialized equipment.

The most novel of the novel agents for acute myeloid leukemia.

PubMed

Perl, Alexander E

2018-03-01

Precious few drugs were successfully developed for acute myeloid leukemia (AML) over the past decades, despite a dramatic expansion of our understanding of its molecular underpinnings during this time. Then in 2017, a wave of new drugs suddenly became approved. This review serves to introduce the newly available drugs, discuss their impact upon therapy, and highlight additional novel agents that are waiting in the wings. Newly approved agents in AML include a tyrosine kinase inhibitor for patients with FMS-like tyrosine kinase 3 (FLT3) mutations, an inhibitor of mutant isocitrate dehydrogenase (IDH2), and two novel agents using antibody-delivered or liposome-delivered cytotoxics. All of these new agents have demonstrable activity in AML and several have improved survival in randomized studies. In addition to these agents, promising data from other inhibitors of FLT3, IDH1, and B-cell lymphoma 2 (BCL2) will be discussed. Response, survival, and symptom burden of AML therapy are all improving through novel agents. As many of the newly approved drugs benefit-specific genetic subsets, a new priority has emerged to increase the speed of diagnostic genomic studies as a means to guide frontline therapy. This will ensure patients are optimally categorized and treated with to the most rational agents.

Modeling Human Decision Processes in Command and Control

DTIC Science & Technology

1983-02-14

principle , calculus of variations, least squares, etc. 7 SALPHATECH, INC. Thus, the...34"""~~~~~~~~~~~~~~~~~. ." -. " ""’./’ ’ • "" -" - -".. "-.... •..... ""........."-. -....... -.............. r ALPHATECH, INC. to equate what a human does with what he should do. Employing this principle "of bounded rationality, the norm’tive-descriptive...mechanism to describe these salient task features. In essence, the SHOR paradigm is derived from the stimulus-response (S-R) principle

Emotion-affected decision making in human simulation.

PubMed

Zhao, Y; Kang, J; Wright, D K

2006-01-01

Human modelling is an interdisciplinary research field. The topic, emotion-affected decision making, was originally a cognitive psychology issue, but is now recognized as an important research direction for both computer science and biomedical modelling. The main aim of this paper is to attempt to bridge the gap between psychology and bioengineering in emotion-affected decision making. The work is based on Ortony's theory of emotions and bounded rationality theory, and attempts to connect the emotion process with decision making. A computational emotion model is proposed, and the initial framework of this model in virtual human simulation within the platform of Virtools is presented.

Rotation sets and phase-locking in an electronic three oscillator system

NASA Astrophysics Data System (ADS)

Ashwin, Peter; Guaschi, John; Phelps, J. M.

1993-07-01

The parameter space of an electronic three oscillator system is investigated and various codimension one and two bifurcations predicted by Baesens, Guckenheimer, Kim and MacKay are identified. Sampled time-series from the experimental systems are recorded and analysed for partial mode-locking or resonance (one or two independent rational relations between the average rates of change of the angles describing the system) using knowledge of where the invariant torus lies and the torus unfolding scheme of Ashwin and Swift. Examples of toroidal and annular chaos are investigated by finding bounds on the size and shape of the rotation set.

Rational non-interventional paternalism: why doctors ought to make judgments of what is best for their patients.

PubMed Central

Savulescu, J

1995-01-01

This paper argues that doctors ought to make all things considered value judgments about what is best for their patients. It illustrates some of the shortcomings of the model of doctor as 'fact-provider'. The 'fact-provider' model fails to take account of the fact that practising medicine necessarily involves making value judgments; that medical practice is a moral practice and requires that doctors reflect on what ought to be done, and that patients can make choices which fail to express their autonomy and which are based on mistaken judgments of value. If doctors are properly to respect patient autonomy and to function as moral agents, they must make evaluations of what their patients ought to do, all things considered. This paper argues for 'rational, non-interventional paternalism'. This is a practice in which doctors form conceptions of what is best for their patients and argue rationally with them. It differs from old-style paternalism in that it is not committed to doing what is best. PMID:8778455

Rational use of inotropic therapy in heart failure.

PubMed

Felker, G M; O'Connor, C M

2001-03-01

Despite their theoretic appeal, agents that increase cardiac contractility (positive inotropes) have consistently been shown to increase mortality when given chronically to patients with heart failure. The routine use of inotropes as heart failure therapy in either the acute or the chronic setting is not supported by the available data. Some appropriate uses of inotropes are as temporary treatment of diuretic-refractory acute heart failure decompensations, or as a bridge to definitive treatment such as revascularization or cardiac transplantation. Although controversial, the use of inotropes as a palliative measure in the small subset of patients with truly end-stage heart failure may be appropriate. An understanding of the appropriate goals of therapy is important for both patients and physicians if rational decisions about the use of inotropes are to be made.

Advances in protease engineering for laundry detergents.

PubMed

Vojcic, Ljubica; Pitzler, Christian; Körfer, Georgette; Jakob, Felix; Ronny Martinez; Maurer, Karl-Heinz; Schwaneberg, Ulrich

2015-12-25

Proteases are essential ingredients in modern laundry detergents. Over the past 30 years, subtilisin proteases employed in the laundry detergent industry have been engineered by directed evolution and rational design to tailor their properties towards industrial demands. This comprehensive review discusses recent success stories in subtilisin protease engineering. Advances in protease engineering for laundry detergents comprise simultaneous improvement of thermal resistance and activity at low temperatures, a rational strategy to modulate pH profiles, and a general hypothesis for how to increase promiscuous activity towards the production of peroxycarboxylic acids as mild bleaching agents. The three protease engineering campaigns presented provide in-depth analysis of protease properties and have identified principles that can be applied to improve or generate enzyme variants for industrial applications beyond laundry detergents. Copyright © 2015 Elsevier B.V. All rights reserved.

Rational design for multifunctional non-liposomal lipid-based nanocarriers for cancer management: theory to practice

PubMed Central

2013-01-01

Nanomedicines have gained more and more attention in cancer therapy thanks to their ability to enhance the tumour accumulation and the intracellular uptake of drugs while reducing their inactivation and toxicity. In parallel, nanocarriers have been successfully employed as diagnostic tools increasing imaging resolution holding great promises both in preclinical research and in clinical settings. Lipid-based nanocarriers are a class of biocompatible and biodegradable vehicles that provide advanced delivery of therapeutic and imaging agents, improving pharmacokinetic profile and safety. One of most promising engineering challenges is the design of innovative and versatile multifunctional targeted nanotechnologies for cancer treatment and diagnosis. This review aims to highlight rational approaches to design multifunctional non liposomal lipid-based nanocarriers providing an update of literature in this field. PMID:24564841

Design of a small molecule against an oncogenic noncoding RNA.

PubMed

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

2016-05-24

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

Précis of Simple heuristics that make us smart.

PubMed

Todd, P M; Gigerenzer, G

2000-10-01

How can anyone be rational in a world where knowledge is limited, time is pressing, and deep thought is often an unattainable luxury? Traditional models of unbounded rationality and optimization in cognitive science, economics, and animal behavior have tended to view decision-makers as possessing supernatural powers of reason, limitless knowledge, and endless time. But understanding decisions in the real world requires a more psychologically plausible notion of bounded rationality. In Simple heuristics that make us smart (Gigerenzer et al. 1999), we explore fast and frugal heuristics--simple rules in the mind's adaptive toolbox for making decisions with realistic mental resources. These heuristics can enable both living organisms and artificial systems to make smart choices quickly and with a minimum of information by exploiting the way that information is structured in particular environments. In this précis, we show how simple building blocks that control information search, stop search, and make decisions can be put together to form classes of heuristics, including: ignorance-based and one-reason decision making for choice, elimination models for categorization, and satisficing heuristics for sequential search. These simple heuristics perform comparably to more complex algorithms, particularly when generalizing to new data--that is, simplicity leads to robustness. We present evidence regarding when people use simple heuristics and describe the challenges to be addressed by this research program.

Trypanosoma Cruzi Cyp51 Inhibitor Derived from a Mycobacterium Tuberculosis Screen Hit

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

Chen, Chiung-Kuang; Doyle, Patricia S.; Yermalitskaya, Liudmila V.

2009-02-18

The two front-line drugs for chronic Trypanosoma cruzi infections are limited by adverse side-effects and declining efficacy. One potential new target for Chagas disease chemotherapy is sterol 14{alpha}-demethylase (CYP51), a cytochrome P450 enzyme involved in biosynthesis of membrane sterols. In a screening effort targeting Mycobacterium tuberculosis CYP51 (CYP51{sub Mt}), we previously identified the N-[4-pyridyl]-formamide moiety as a building block capable of delivering a variety of chemotypes into the CYP51 active site. In that work, the binding modes of several second generation compounds carrying this scaffold were determined by high-resolution co-crystal structures with CYP51{sub Mt}. Subsequent assays against the CYP51 orthologuemore » in T. cruzi, CYP51{sub Tc}, demonstrated that two of the compounds tested in the earlier effort bound tightly to this enzyme. Both were tested in vitro for inhibitory effects against T. cruzi and the related protozoan parasite Trypanosoma brucei, the causative agent of African sleeping sickness. One of the compounds had potent, selective anti-T. cruzi activity in infected mouse macrophages. Cure of treated host cells was confirmed by prolonged incubation in the absence of the inhibiting compound. Discrimination between T. cruzi and T. brucei CYP51 by the inhibitor was largely based on the variability (phenylalanine versus isoleucine) of a single residue at a critical position in the active site. CYP51{sub Mt}-based crystal structure analysis revealed that the functional groups of the two tightly bound compounds are likely to occupy different spaces in the CYP51 active site, suggesting the possibility of combining the beneficial features of both inhibitors in a third generation of compounds to achieve more potent and selective inhibition of CYP51{sub Tc}. Enzyme sterol 14{alpha}-demethylase (CYP51) is a well-established target for anti-fungal therapy and is a prospective target for Chagas disease therapy. We previously identified a chemical scaffold capable of delivering a variety of chemical structures into the CYP51 active site. In this work the binding modes of several second generation compounds carrying this scaffold were determined in high-resolution co-crystal structures with CYP51 of Mycobacterium tuberculosis. Subsequent assays against CYP51 in Trypanosoma cruzi, the agent of Chagas disease, demonstrated that two of the compounds bound tightly to the enzyme. Both were tested for inhibitory effects against T. cruzi and the related protozoan parasite Trypanosoma brucei. One of the compounds had potent, selective anti-T. cruzi activity in infected mouse macrophages. This compound is currently being evaluated in animal models of Chagas disease. Discrimination between T. cruzi and T. brucei CYP51 by the inhibitor was largely based on the variability of a single amino acid residue at a critical position in the active site. Our work is aimed at rational design of potent and highly selective CYP51 inhibitors with potential to become therapeutic drugs. Drug selectivity to prevent host-pathogen cross-reactivity is pharmacologically important, because CYP51 is present in human host.« less

IR signature of the photoionization-induced hydrophobic-->hydrophilic site switching in phenol-Arn clusters

NASA Astrophysics Data System (ADS)

Ishiuchi, Shun-ichi; Sakai, Makoto; Tsuchida, Yuji; Takeda, Akihiro; Kawashima, Yasutake; Dopfer, Otto; Müller-Dethlefs, Klaus; Fujii, Masaaki

2007-09-01

IR spectra of phenol-Arn (PhOH-Arn) clusters with n =1 and 2 were measured in the neutral and cationic electronic ground states in order to determine the preferential intermolecular ligand binding motifs, hydrogen bonding (hydrophilic interaction) versus π bonding (hydrophobic interaction). Analysis of the vibrational frequencies of the OH stretching motion, νOH, observed in nanosecond IR spectra demonstrates that neutral PhOH-Ar and PhOH -Ar2 as well as cationic PhOH +-Ar have a π-bound structure, in which the Ar atoms bind to the aromatic ring. In contrast, the PhOH +-Ar2 cluster cation is concluded to have a H-bound structure, in which one Ar atom is hydrogen-bonded to the OH group. This π →H binding site switching induced by ionization was directly monitored in real time by picosecond time-resolved IR spectroscopy. The π-bound νOH band is observed just after the ionization and disappears simultaneously with the appearance of the H-bound νOH band. The analysis of the picosecond IR spectra demonstrates that (i) the π →H site switching is an elementary reaction with a time constant of ˜7ps, which is roughly independent of the available internal vibrational energy, (ii) the barrier for the isomerization reaction is rather low(<100cm-1), (iii) both the position and the width of the H-bound νOH band change with the delay time, and the time evolution of these spectral changes can be rationalized by intracluster vibrational energy redistribution occurring after the site switching. The observation of the ionization-induced switch from π bonding to H bonding in the PhOH +-Ar2 cation corresponds to the first manifestation of an intermolecular isomerization reaction in a charged aggregate.

Nonlinear multi-analysis of agent-based financial market dynamics by epidemic system

NASA Astrophysics Data System (ADS)

Lu, Yunfan; Wang, Jun; Niu, Hongli

2015-10-01

Based on the epidemic dynamical system, we construct a new agent-based financial time series model. In order to check and testify its rationality, we compare the statistical properties of the time series model with the real stock market indices, Shanghai Stock Exchange Composite Index and Shenzhen Stock Exchange Component Index. For analyzing the statistical properties, we combine the multi-parameter analysis with the tail distribution analysis, the modified rescaled range analysis, and the multifractal detrended fluctuation analysis. For a better perspective, the three-dimensional diagrams are used to present the analysis results. The empirical research in this paper indicates that the long-range dependence property and the multifractal phenomenon exist in the real returns and the proposed model. Therefore, the new agent-based financial model can recurrence some important features of real stock markets.

Quantum Barro-Gordon game in monetary economics

NASA Astrophysics Data System (ADS)

Samadi, Ali Hussein; Montakhab, Afshin; Marzban, Hussein; Owjimehr, Sakine

2018-01-01

Classical game theory addresses decision problems in multi-agent environment where one rational agent's decision affects other agents' payoffs. Game theory has widespread application in economic, social and biological sciences. In recent years quantum versions of classical games have been proposed and studied. In this paper, we consider a quantum version of the classical Barro-Gordon game which captures the problem of time inconsistency in monetary economics. Such time inconsistency refers to the temptation of weak policy maker to implement high inflation when the public expects low inflation. The inconsistency arises when the public punishes the weak policy maker in the next cycle. We first present a quantum version of the Barro-Gordon game. Next, we show that in a particular case of the quantum game, time-consistent Nash equilibrium could be achieved when public expects low inflation, thus resolving the game.

Designed Long-Lived Emission from CdSe Quantum Dots through Reversible Electronic Energy Transfer with a Surface-Bound Chromophore.

PubMed

La Rosa, Marcello; Denisov, Sergey A; Jonusauskas, Gediminas; McClenaghan, Nathan D; Credi, Alberto

2018-03-12

The size-tunable emission of luminescent quantum dots (QDs) makes them highly interesting for applications that range from bioimaging to optoelectronics. For the same applications, engineering their luminescence lifetime, in particular, making it longer, would be as important; however, no rational approach to reach this goal is available to date. We describe a strategy to prolong the emission lifetime of QDs through electronic energy shuttling to the triplet excited state of a surface-bound molecular chromophore. To implement this idea, we made CdSe QDs of different sizes and carried out self-assembly with a pyrene derivative. We observed that the conjugates exhibit delayed luminescence, with emission decays that are prolonged by more than 3 orders of magnitude (lifetimes up to 330 μs) compared to the parent CdSe QDs. The mechanism invokes unprecedented reversible quantum dot to organic chromophore electronic energy transfer. © 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

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

Matthews, Melissa M.; Thomas, Justin M.; Zheng, Yuxuan

Adenosine deaminases acting on RNA (ADARs) are editing enzymes that convert adenosine to inosine in duplex RNA, a modification reaction with wide-ranging consequences in RNA function. Understanding of the ADAR reaction mechanism, the origin of editing-site selectivity, and the effect of mutations is limited by the lack of high-resolution structural data for complexes of ADARs bound to substrate RNAs. In this paper, we describe four crystal structures of the human ADAR2 deaminase domain bound to RNA duplexes bearing a mimic of the deamination reaction intermediate. These structures, together with structure-guided mutagenesis and RNA-modification experiments, explain the basis of the ADARmore » deaminase domain's dsRNA specificity, its base-flipping mechanism, and its nearest-neighbor preferences. In addition, we identified an ADAR2-specific RNA-binding loop near the enzyme active site, thus rationalizing differences in selectivity observed between different ADARs. In conclusion, our results provide a structural framework for understanding the effects of ADAR mutations associated with human disease.« less

Differential proteomics analysis of the surface heterogeneity of dextran iron oxide nanoparticles and the implications for their in vivo clearance

PubMed Central

Simberg, Dmitri; Park, Ji-Ho; Karmali, Priya P.; Zhang, Wan-Ming; Merkulov, Sergei; McCrae, Keith; Bhatia, Sangeeta; Sailor, Michael; Ruoslahti, Erkki

2009-01-01

In order to understand the role of plasma proteins in the rapid liver clearance of dextran-coated superparamagnetic iron oxide (SPIO) in vivo, we analyzed the full repertoire of SPIO-binding blood proteins using novel two-dimensional differential mass spectrometry approach. The identified proteins showed specificity for surface domains of the nanoparticles: mannan-binding lectins bound to the dextran coating, histidine-rich glycoprotein and kininogen bound to the iron oxide part, and the complement lectin and contact clotting factors were secondary binders. Nanoparticle clearance studies in knockout mice suggested that these proteins, as well as several previously identified opsonins, do not play a significant role in the SPIO clearance. However, both the dextran coat and the iron oxide core remained accessible to specific probes after incubation of SPIO in plasma, suggesting that the nanoparticle surface could be available for recognition by macrophages, regardless of protein coating. These data provide guidance to rational design of bioinert, long-circulating nanoparticles. PMID:19394687

Differential proteomics analysis of the surface heterogeneity of dextran iron oxide nanoparticles and the implications for their in vivo clearance.

PubMed

Simberg, Dmitri; Park, Ji-Ho; Karmali, Priya P; Zhang, Wan-Ming; Merkulov, Sergei; McCrae, Keith; Bhatia, Sangeeta N; Sailor, Michael; Ruoslahti, Erkki

2009-08-01

In order to understand the role of plasma proteins in the rapid liver clearance of dextran-coated superparamagnetic iron oxide (SPIO) in vivo, we analyzed the full repertoire of SPIO-binding blood proteins using novel two-dimensional differential mass spectrometry approach. The identified proteins showed specificity for surface domains of the nanoparticles: mannan-binding lectins bound to the dextran coating, histidine-rich glycoprotein and kininogen bound to the iron oxide part, and the complement lectin and contact clotting factors were secondary binders. Nanoparticle clearance studies in knockout mice suggested that these proteins, as well as several previously identified opsonins, do not play a significant role in the SPIO clearance. However, both the dextran coat and the iron oxide core remained accessible to specific probes after incubation of SPIO in plasma, suggesting that the nanoparticle surface could be available for recognition by macrophages, regardless of protein coating. These data provide guidance to rational design of bioinert, long-circulating nanoparticles.

Parametric symmetries in exactly solvable real and PT symmetric complex potentials

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

Yadav, Rajesh Kumar, E-mail: rajeshastrophysics@gmail.com; Khare, Avinash, E-mail: khare@physics.unipune.ac.in; Bagchi, Bijan, E-mail: bbagchi123@gmail.com

In this paper, we discuss the parametric symmetries in different exactly solvable systems characterized by real or complex PT symmetric potentials. We focus our attention on the conventional potentials such as the generalized Pöschl Teller (GPT), Scarf-I, and PT symmetric Scarf-II which are invariant under certain parametric transformations. The resulting set of potentials is shown to yield a completely different behavior of the bound state solutions. Further, the supersymmetric partner potentials acquire different forms under such parametric transformations leading to new sets of exactly solvable real and PT symmetric complex potentials. These potentials are also observed to be shape invariantmore » (SI) in nature. We subsequently take up a study of the newly discovered rationally extended SI potentials, corresponding to the above mentioned conventional potentials, whose bound state solutions are associated with the exceptional orthogonal polynomials (EOPs). We discuss the transformations of the corresponding Casimir operator employing the properties of the so(2, 1) algebra.« less

[The effect of copper on the metabolism of iodine, carbohydrates and proteins in rats].

PubMed

Esipenko, B E; Marsakova, N V

1990-01-01

Experiments on 156 rats maintained at ration with copper deficiency have demonstrated a decrease in the values of iodine metabolism in organs and tissues excluding the liver where a sharp increase in the concentration and content of inorganic iodine was observed. A disturbance in indices of carbohydrate and proteins metabolism in the organism of animals is marked. A direct relationship with a correlation coefficient equaling 0.87-1.00 is determined between changes in the concentration of protein-bound iodine in blood and concentration of glycogen in the liver, skeletal muscles, albumins, alpha 1-, alpha 2-globulins, urea concentration; an inverse relationship with glucose, activity of blood lipo-dehydrogenase and liver mitochondria, aldolase, concentration of pyruvic and lactic acids is established as well. It is concluded that copper deficiency can exert both a direct effect on metabolic processes (as data from literature testify) and an indirect one disturbing iodine metabolism, i. e. sharply decreasing protein-bound iodine production by the thyroid gland.

Rational Design and Development of Reactive Multifunctional Micellar Composite Nano-particles for Destruction of Bio-agents

DTIC Science & Technology

2015-02-01

nanoparticles, , multifunction porous metal oxide -silica composites, porous silicon - Titania and PSi-silver heterojunctions ) have been successfully...nanoparticles, multifunctional porous metal oxide -silica composites, porous silicon -Titania and PSi-silver heterojunctions ) have been successfully...generated charge separation and enhance the photocatalytic oxidation . In the PSi-Ag heterojunctions , Ag can not only act as time-honored antibacterial

Consentaneous Agent-Based and Stochastic Model of the Financial Markets

PubMed Central

Gontis, Vygintas; Kononovicius, Aleksejus

2014-01-01

We are looking for the agent-based treatment of the financial markets considering necessity to build bridges between microscopic, agent based, and macroscopic, phenomenological modeling. The acknowledgment that agent-based modeling framework, which may provide qualitative and quantitative understanding of the financial markets, is very ambiguous emphasizes the exceptional value of well defined analytically tractable agent systems. Herding as one of the behavior peculiarities considered in the behavioral finance is the main property of the agent interactions we deal with in this contribution. Looking for the consentaneous agent-based and macroscopic approach we combine two origins of the noise: exogenous one, related to the information flow, and endogenous one, arising form the complex stochastic dynamics of agents. As a result we propose a three state agent-based herding model of the financial markets. From this agent-based model we derive a set of stochastic differential equations, which describes underlying macroscopic dynamics of agent population and log price in the financial markets. The obtained solution is then subjected to the exogenous noise, which shapes instantaneous return fluctuations. We test both Gaussian and q-Gaussian noise as a source of the short term fluctuations. The resulting model of the return in the financial markets with the same set of parameters reproduces empirical probability and spectral densities of absolute return observed in New York, Warsaw and NASDAQ OMX Vilnius Stock Exchanges. Our result confirms the prevalent idea in behavioral finance that herding interactions may be dominant over agent rationality and contribute towards bubble formation. PMID:25029364

Rosetta comparative modeling for library design: Engineering alternative inducer specificity in a transcription factor.

PubMed

Jha, Ramesh K; Chakraborti, Subhendu; Kern, Theresa L; Fox, David T; Strauss, Charlie E M

2015-07-01

Structure-based rational mutagenesis for engineering protein functionality has been limited by the scarcity and difficulty of obtaining crystal structures of desired proteins. On the other hand, when high-throughput selection is possible, directed evolution-based approaches for gaining protein functionalities have been random and fortuitous with limited rationalization. We combine comparative modeling of dimer structures, ab initio loop reconstruction, and ligand docking to select positions for mutagenesis to create a library focused on the ligand-contacting residues. The rationally reduced library requirement enabled conservative control of the substitutions by oligonucleotide synthesis and bounding its size within practical transformation efficiencies (∼ 10(7) variants). This rational approach was successfully applied on an inducer-binding domain of an Acinetobacter transcription factor (TF), pobR, which shows high specificity for natural effector molecule, 4-hydroxy benzoate (4HB), but no native response to 3,4-dihydroxy benzoate (34DHB). Selection for mutants with high transcriptional induction by 34DHB was carried out at the single-cell level under flow cytometry (via green fluorescent protein expression under the control of pobR promoter). Critically, this selection protocol allows both selection for induction and rejection of constitutively active mutants. In addition to gain-of-function for 34DHB induction, the selected mutants also showed enhanced sensitivity and response for 4HB (native inducer) while no sensitivity was observed for a non-targeted but chemically similar molecule, 2-hydroxy benzoate (2HB). This is unique application of the Rosetta modeling protocols for library design to engineer a TF. Our approach extends applicability of the Rosetta redesign protocol into regimes without a priori precision structural information. © 2015 Wiley Periodicals, Inc.

Smart Contrast Agents for Magnetic Resonance Imaging.

PubMed

Bonnet, Célia S; Tóth, Éva

2016-01-01

By visualizing bioactive molecules or biological parameters in vivo, molecular imaging is searching for information at the molecular level in living organisms. In addition to contributing to earlier and more personalized diagnosis in medicine, it also helps understand and rationalize the molecular factors underlying physiological and pathological processes. In magnetic resonance imaging (MRI), complexes of paramagnetic metal ions, mostly lanthanides, are commonly used to enhance the intrinsic image contrast. They rely either on the relaxation effect of these metal chelates (T(1) agents), or on the phenomenon of paramagnetic chemical exchange saturation transfer (PARACEST agents). In both cases, responsive molecular magnetic resonance imaging probes can be designed to report on various biomarkers of biological interest. In this context, we review recent work in the literature and from our group on responsive T(1) and PARACEST MRI agents for the detection of biogenic metal ions (such as calcium or zinc), enzymatic activities, or neurotransmitter release. These examples illustrate the general strategies that can be applied to create molecular imaging agents with an MRI detectable response to biologically relevant parameters.

Mechanism Design for Task Procurement with Flexible Quality of Service

NASA Astrophysics Data System (ADS)

Gerding, Enrico H.; Larson, Kate; Rogers, Alex; Jennings, Nicholas R.

In this paper, we consider the problem where an agent wishes to complete a single computational task, but lacks the required resources. Instead, it must contract self-interested service providers, who are able to flexibly manipulate the quality of service they deliver, in order to maximise their own utility. We extend an existing model to allow for multiple such service providers to be contracted for the same task, and derive optimal task procurement mechanisms in the setting where the agent has full knowledge of the cost functions of these service providers (considering both simultaneous and sequential procurement). We then extend these results to the incomplete information setting where the agent must elicit cost information from the service providers, and we characterise a family of incentive-compatible and individually-rational mechanisms. We show empirically that sequential procurement always generates greater utility for the agent compared to simultaneous procurement, and that over a range of settings, contracting multiple providers is preferable to contracting just one.

Consensus in evolving networks of mobile agents

NASA Astrophysics Data System (ADS)

Baronchelli, Andrea; Díaz-Guilera, Albert

2012-02-01

Populations of mobile and communicating agents describe a vast array of technological and natural systems, ranging from sensor networks to animal groups. Here, we investigate how a group-level agreement may emerge in the continuously evolving networks defined by the local interactions of the moving individuals. We adopt a general scheme of motion in two dimensions and we let the individuals interact through the minimal naming game, a prototypical scheme to investigate social consensus. We distinguish different regimes of convergence determined by the emission range of the agents and by their mobility, and we identify the corresponding scaling behaviors of the consensus time. In the same way, we rationalize also the behavior of the maximum memory used during the convergence process, which determines the minimum cognitive/storage capacity needed by the individuals. Overall, we believe that the simple and general model presented in this talk can represent a helpful reference for a better understanding of the behavior of populations of mobile agents.

Consensus in networks of mobile communicating agents

NASA Astrophysics Data System (ADS)

Baronchelli, Andrea; Díaz-Guilera, Albert

2012-01-01

Populations of mobile and communicating agents describe a vast array of technological and natural systems, ranging from sensor networks to animal groups. Here, we investigate how a group-level agreement may emerge in the continuously evolving network defined by the local interactions of the moving individuals. We adopt a general scheme of motion in two dimensions and we let the individuals interact through the minimal naming game, a prototypical scheme to investigate social consensus. We distinguish different regimes of convergence determined by the emission range of the agents and by their mobility, and we identify the corresponding scaling behaviors of the consensus time. In the same way, we rationalize also the behavior of the maximum memory used during the convergence process, which determines the minimum cognitive/storage capacity needed by the individuals. Overall, we believe that the simple and general model presented in this paper can represent a helpful reference for a better understanding of the behavior of populations of mobile agents.

[Research of preparation craft of Danshen phenolic acid fast release unit in multi-drug delivery system of Tongmai micro-pellets].

PubMed

Chen, Bin; Xiao, Wei; Jia, Xiao-Bin; Huang, Yang

2012-07-01

To prepare Danshen phenolic acid fast release micro-pellets and study its preparation craft. The factors which could impact yield, extrude shaping, dissolution of Danshen phenolic acid micro-pellets such as wetting agent, drug loading dose, adjuvant, lactose dose, disintegrant, CMS-Na dose and wetting agent dose was investigated. The optimum preparation craft of Danshen phenolic acid fast release micro-pellets was screened out by orhogonal design. Formula of Danshen phenolic acid fast release micro-pellets was calculated as volume dose 50 g. The formula was as follows: principal agent 22.5 g, lactose 5 g, CMS-Na 2 g, MCC 20.5 g, 27 mL 30% ethanol as wetting agent. Extrusion-spheronization was applied. The optimum conditions were screened out as follows: extrusion frequency (25 Hz), spheronization machine frequency (50 Hz), spheronization time (4 min). The process was scientific and rational. The preparation is stable settles basis for multi-drug delivery system of Tongmai micro-pellets.

Evolutionary game dynamics of controlled and automatic decision-making

NASA Astrophysics Data System (ADS)

Toupo, Danielle F. P.; Strogatz, Steven H.; Cohen, Jonathan D.; Rand, David G.

2015-07-01

We integrate dual-process theories of human cognition with evolutionary game theory to study the evolution of automatic and controlled decision-making processes. We introduce a model in which agents who make decisions using either automatic or controlled processing compete with each other for survival. Agents using automatic processing act quickly and so are more likely to acquire resources, but agents using controlled processing are better planners and so make more effective use of the resources they have. Using the replicator equation, we characterize the conditions under which automatic or controlled agents dominate, when coexistence is possible and when bistability occurs. We then extend the replicator equation to consider feedback between the state of the population and the environment. Under conditions in which having a greater proportion of controlled agents either enriches the environment or enhances the competitive advantage of automatic agents, we find that limit cycles can occur, leading to persistent oscillations in the population dynamics. Critically, however, these limit cycles only emerge when feedback occurs on a sufficiently long time scale. Our results shed light on the connection between evolution and human cognition and suggest necessary conditions for the rise and fall of rationality.

Rational Constraints and the Evolution of Fairness in the Ultimatum Game.

PubMed

Tomlin, Damon

2015-01-01

Behavior in the Ultimatum Game has been well-studied experimentally, and provides a marked contrast between the theoretical model of a self-interested economic agent and that of an actual human concerned with social norms such as fairness. How did such norms evolve, when punishing unfair behavior can be costly to the punishing agent? The work described here simulated a series of Ultimatum Games, in which populations of agents earned resources based on their preferences for proposing and accepting (or rejecting) offers of various sizes. Two different systems governing the acceptance or rejection of offers were implemented. Under one system, the probability that an agent accepted an offer of a given size was independent of the probabilities of accepting the other possible offers. Under the other system, a simple, ordinal constraint was placed on the acceptance probabilities such that a given offer was at least as likely to be accepted as a smaller offer. For simulations under either system, agents' preferences and their corresponding behavior evolved over multiple generations. Populations without the ordinal constraint came to emulate maximizing economic agents, while populations with the constraint came to resemble the behavior of human players.

Evolutionary game dynamics of controlled and automatic decision-making.

PubMed

Toupo, Danielle F P; Strogatz, Steven H; Cohen, Jonathan D; Rand, David G

2015-07-01

We integrate dual-process theories of human cognition with evolutionary game theory to study the evolution of automatic and controlled decision-making processes. We introduce a model in which agents who make decisions using either automatic or controlled processing compete with each other for survival. Agents using automatic processing act quickly and so are more likely to acquire resources, but agents using controlled processing are better planners and so make more effective use of the resources they have. Using the replicator equation, we characterize the conditions under which automatic or controlled agents dominate, when coexistence is possible and when bistability occurs. We then extend the replicator equation to consider feedback between the state of the population and the environment. Under conditions in which having a greater proportion of controlled agents either enriches the environment or enhances the competitive advantage of automatic agents, we find that limit cycles can occur, leading to persistent oscillations in the population dynamics. Critically, however, these limit cycles only emerge when feedback occurs on a sufficiently long time scale. Our results shed light on the connection between evolution and human cognition and suggest necessary conditions for the rise and fall of rationality.

Damage spreading and opinion dynamics on scale-free networks

NASA Astrophysics Data System (ADS)

Fortunato, Santo

2005-03-01

We study damage spreading among the opinions of a system of agents, subjected to the dynamics of the Krause-Hegselmann consensus model. The damage consists in a sharp change of the opinion of one or more agents in the initial random opinion configuration, supposedly due to some external factors and/or events. This may help to understand for instance under which conditions special shocking events or targeted propaganda are able to influence the results of elections. For agents lying on the nodes of a Barabási-Albert network, there is a damage spreading transition at a low value εd of the confidence bound parameter. Interestingly, we find as well that there is some critical value εs above which the initial perturbation manages to propagate to all other agents.

Rapid innovation diffusion in social networks.

PubMed

Kreindler, Gabriel E; Young, H Peyton

2014-07-22

Social and technological innovations often spread through social networks as people respond to what their neighbors are doing. Previous research has identified specific network structures, such as local clustering, that promote rapid diffusion. Here we derive bounds that are independent of network structure and size, such that diffusion is fast whenever the payoff gain from the innovation is sufficiently high and the agents' responses are sufficiently noisy. We also provide a simple method for computing an upper bound on the expected time it takes for the innovation to become established in any finite network. For example, if agents choose log-linear responses to what their neighbors are doing, it takes on average less than 80 revision periods for the innovation to diffuse widely in any network, provided that the error rate is at least 5% and the payoff gain (relative to the status quo) is at least 150%. Qualitatively similar results hold for other smoothed best-response functions and populations that experience heterogeneous payoff shocks.

Optimization in modeling the ribs-bounded contour from computer tomography scan

NASA Astrophysics Data System (ADS)

Bilinskas, M. J.; Dzemyda, G.

2016-10-01

In this paper a method for analyzing transversal plane images from computer tomography scans is presented. A mathematical model that describes the ribs-bounded contour was created and the problem of approximation is solved by finding out the optimal parameters of the model in the least-squares sense. Such model would be useful in registration of images independently on the patient position on the bed and on the radio-contrast agent injection. We consider the slices, where ribs are visible, because many important internal organs are located here: liver, heart, stomach, pancreas, lung, etc.

Perspective on the pipeline of drugs being developed with modulation of DNA damage as a target.

PubMed

Plummer, Ruth

2010-09-15

Inhibitors of various elements of the DNA repair pathways have entered clinical development or are in late preclinical stages of drug development. It was initially considered that agents targeting DNA repair would act to overcome tumor resistance to chemotherapy and radiotherapy. More recent data have shown that targeting DNA repair pathways can be effective in selected tumors via a synthetically lethal route, with single agent activity having been shown with poly-ADP ribose polymerase (PARP) inhibitors. An increased understanding of the biology and interaction of the DNA repair pathways also means that rational combination of DNA repair inhibitors may also give great benefit in the clinic. ©2010 AACR.

Discrete Model of Opinion Changes Using Knowledge and Emotions as Control Variables

PubMed Central

Sobkowicz, Pawel

2012-01-01

We present a new model of opinion changes dependent on the agents emotional state and their information about the issue in question. Our goal is to construct a simple, yet nontrivial and flexible representation of individual attitude dynamics for agent based simulations, that could be used in a variety of social environments. The model is a discrete version of the cusp catastrophe model of opinion dynamics in which information is treated as the normal factor while emotional arousal (agitation level determining agent receptiveness and rationality) is treated as the splitting factor. Both variables determine the resulting agent opinion, which itself can be in favor of the studied position, against it, or neutral. Thanks to the flexibility of implementing communication between the agents, the model is potentially applicable in a wide range of situations. As an example of the model application, we study the dynamics of a set of agents communicating among themselves via messages. In the example, we chose the simplest, fully connected communication topology, to focus on the effects of the individual opinion dynamics, and to look for stable final distributions of agents with different emotions, information and opinions. Even for such simplified system, the model shows complex behavior, including phase transitions due to symmetry breaking by external propaganda. PMID:22984516

Discrete model of opinion changes using knowledge and emotions as control variables.

PubMed

Sobkowicz, Pawel

2012-01-01

We present a new model of opinion changes dependent on the agents emotional state and their information about the issue in question. Our goal is to construct a simple, yet nontrivial and flexible representation of individual attitude dynamics for agent based simulations, that could be used in a variety of social environments. The model is a discrete version of the cusp catastrophe model of opinion dynamics in which information is treated as the normal factor while emotional arousal (agitation level determining agent receptiveness and rationality) is treated as the splitting factor. Both variables determine the resulting agent opinion, which itself can be in favor of the studied position, against it, or neutral. Thanks to the flexibility of implementing communication between the agents, the model is potentially applicable in a wide range of situations. As an example of the model application, we study the dynamics of a set of agents communicating among themselves via messages. In the example, we chose the simplest, fully connected communication topology, to focus on the effects of the individual opinion dynamics, and to look for stable final distributions of agents with different emotions, information and opinions. Even for such simplified system, the model shows complex behavior, including phase transitions due to symmetry breaking by external propaganda.

Combined-modality treatment of solid tumors using radiotherapy and molecular targeted agents.

PubMed

Ma, Brigette B Y; Bristow, Robert G; Kim, John; Siu, Lillian L

2003-07-15

Molecular targeted agents have been combined with radiotherapy (RT) in recent clinical trials in an effort to optimize the therapeutic index of RT. The appeal of this strategy lies in their potential target specificity and clinically acceptable toxicity. This article integrates the salient, published research findings into the underlying molecular mechanisms, preclinical efficacy, and clinical applicability of combining RT with molecular targeted agents. These agents include inhibitors of intracellular signal transduction molecules, modulators of apoptosis, inhibitors of cell cycle checkpoints control, antiangiogenic agents, and cyclo-oxygenase-2 inhibitors. Molecular targeted agents can have direct effects on the cytoprotective and cytotoxic pathways implicated in the cellular response to ionizing radiation (IR). These pathways involve cellular proliferation, DNA repair, cell cycle progression, nuclear transcription, tumor angiogenesis, and prostanoid-associated inflammation. These pathways can also converge to alter RT-induced apoptosis, terminal growth arrest, and reproductive cell death. Pharmacologic modulation of these pathways may potentially enhance tumor response to RT though inhibition of tumor repopulation, improvement of tumor oxygenation, redistribution during the cell cycle, and alteration of intrinsic tumor radiosensitivity. Combining RT and molecular targeted agents is a rational approach in the treatment of solid tumors. Translation of this approach from promising preclinical data to clinical trials is actively underway.

Probing the effects of surface hydrophobicity and tether orientation on antibody-antigen binding

NASA Astrophysics Data System (ADS)

Bush, Derek B.; Knotts, Thomas A.

2017-04-01

Antibody microarrays have the potential to revolutionize molecular detection for many applications, but their current use is limited by poor reliability, and efforts to change this have not yielded fruitful results. One difficulty which limits the rational engineering of next-generation devices is that little is known, at the molecular level, about the antibody-antigen binding process near solid surfaces. Atomic-level structural information is scant because typical experimental techniques (X-ray crystallography and NMR) cannot be used to image proteins bound to surfaces. To overcome this limitation, this study uses molecular simulation and an advanced, experimentally validated, coarse-grain, protein-surface model to compare fab-lysozyme binding in bulk solution and when the fab is tethered to hydrophobic and hydrophilic surfaces. The results show that the tether site in the fab, as well as the surface hydrophobicity, significantly impacts the binding process and suggests that the optimal design involves tethering fabs upright on a hydrophilic surface. The results offer an unprecedented, molecular-level picture of the binding process and give hope that the rational design of protein-microarrays is possible.

A gadolinium(III) complex of a carboxylic-phosphorus acid derivative of diethylenetriamine covalently bound to inulin, a potential macromolecular MRI contrast agent.

PubMed

Lebdusková, Petra; Kotek, Jan; Hermann, Petr; Vander Elst, Luce; Muller, Robert N; Lukes, Ivan; Peters, Joop A

2004-01-01

A novel conjugate of a polysaccharide and a Gd(III) chelate with potential as contrast agent for magnetic resonance imaging (MRI) was synthesized. The structure of the chelate was derived from H5DTPA by replacing the central pendant arm by a phosphinic acid functional group, which was covalently bound to the polysaccharide inulin. On the average, each monosaccharide unit of the inulin was attached to approximately one (0.9) chelate moiety. The average molecular weight is 23110 and the average number of Gd3+ ions per molecule is 24. The ligand binds the Gd3+ ion in an octadentate fashion via three nitrogen atoms, four carboxylate oxygen atoms, and one P-O oxygen atom, and its first coordination sphere is completed by a water molecule. This compound shows promising properties for application as a contrast agent for MRI thanks to a favorable residence lifetime of this water molecule (170 ns at 298 K), a relatively long rotational correlation time (866 ps at 298 K), and the presence of two water molecules in the second coordination sphere of the Gd3+ ion. Furthermore, its stability toward transmetalation with Zn(II) is as high as that of the clinically used [Gd(DTPA)(H2O)]2-.

Ant-inspired density estimation via random walks.

PubMed

Musco, Cameron; Su, Hsin-Hao; Lynch, Nancy A

2017-10-03

Many ant species use distributed population density estimation in applications ranging from quorum sensing, to task allocation, to appraisal of enemy colony strength. It has been shown that ants estimate local population density by tracking encounter rates: The higher the density, the more often the ants bump into each other. We study distributed density estimation from a theoretical perspective. We prove that a group of anonymous agents randomly walking on a grid are able to estimate their density within a small multiplicative error in few steps by measuring their rates of encounter with other agents. Despite dependencies inherent in the fact that nearby agents may collide repeatedly (and, worse, cannot recognize when this happens), our bound nearly matches what would be required to estimate density by independently sampling grid locations. From a biological perspective, our work helps shed light on how ants and other social insects can obtain relatively accurate density estimates via encounter rates. From a technical perspective, our analysis provides tools for understanding complex dependencies in the collision probabilities of multiple random walks. We bound the strength of these dependencies using local mixing properties of the underlying graph. Our results extend beyond the grid to more general graphs, and we discuss applications to size estimation for social networks, density estimation for robot swarms, and random walk-based sampling for sensor networks.

Anxiety and disturbed behavior in the elderly.

PubMed

Salzberger, G J

1981-04-01

The struggle between the elderly patient and his social environment leads to a loss of self-esteem accompanied by fear and anger. These feelings, together with a rational and irrational search for aid, produce a symptom complex which is a depressive or anxiety syndrome. The physician must reinforce and hasten natural recovery processes. Drug therapy may pave the way. Phenothiazines should be avoided. Among the benzodiazepines, shorter-acting agents are preferable.

Exploring utilitarian and hedonic antecedents for adopting information from a recommendation agent and unplanned purchase behaviour

NASA Astrophysics Data System (ADS)

Huang, Li-Ting

2016-01-01

Research indicated that in order for properly utilizing recommendation agents (RAs), customers must rationally evaluate capability and suggestions of RAs during the interaction process. However, enjoying interactive processes and interface is also important. Methods for increasing user enjoyment of RAs are yet unknown. This study investigated the influences of utilitarian and hedonic factors on intention to adopt RAs suggestions and their antecedents. Involvement influences relative importance of utilitarian and hedonic factors. Contrary to common assumptions, customers may make unplanned purchases, rather than rational purchase. A field experiment with 2 × 2 × 2 factorial design reveals main findings. First, information diagnosticity and enjoyment enhance adoption intention simultaneously. Information diagnosticity is more important than enjoyment. Diagnosticity was determined by outcome similarity, and enjoyment was determined by both outcome similarity and atmospherics. The context of interacting with RAs is important. Outcome similarity even directly affects adoption intention. Second, highly involved users considered enjoyment and diagnosticity when forming adoption intentions, while users with low involvement only considered enjoyment. Third, information cascades altered the relationship between adoption intention and unplanned purchases. Most customers change selection after seeing ratings from other customers, even if they originally strongly want to adoption suggestion from RAs. Theoretical and managerial implications are proposed.

In the Opponent's Shoes: Increasing the Behavioral Validity of Attackers' Judgments in Counterterrorism Models.

PubMed

Sri Bhashyam, Sumitra; Montibeller, Gilberto

2016-04-01

A key objective for policymakers and analysts dealing with terrorist threats is trying to predict the actions that malicious agents may take. A recent trend in counterterrorism risk analysis is to model the terrorists' judgments, as these will guide their choices of such actions. The standard assumptions in most of these models are that terrorists are fully rational, following all the normative desiderata required for rational choices, such as having a set of constant and ordered preferences, being able to perform a cost-benefit analysis of their alternatives, among many others. However, are such assumptions reasonable from a behavioral perspective? In this article, we analyze the types of assumptions made across various counterterrorism analytical models that represent malicious agents' judgments and discuss their suitability from a descriptive point of view. We then suggest how some of these assumptions could be modified to describe terrorists' preferences more accurately, by drawing knowledge from the fields of behavioral decision research, politics, philosophy of choice, public choice, and conflict management in terrorism. Such insight, we hope, might help make the assumptions of these models more behaviorally valid for counterterrorism risk analysis. © 2016 The Authors Wound Repair and Regeneration published by Wiley Periodicals, Inc. on behalf of The Wound Healing Society.

Empathy emerges spontaneously in the ultimatum game: small groups and networks.

PubMed

Iranzo, Jaime; Floría, Luis M; Moreno, Yamir; Sánchez, Angel

2012-01-01

The Ultimatum game, in which one subject proposes how to share a pot and the other has veto power on the proposal, in which case both lose everything, is a paradigmatic scenario to probe the degree of cooperation and altruism in human subjects. It has been shown that if individuals are empathic, i.e., they play the game having in mind how their opponent will react by offering an amount that they themselves would accept, then non-rational large offers well above the smallest possible ones are evolutionarily selected. We here show that empathy itself may be selected and need not be exogenously imposed provided that interactions take place only with a fraction of the total population, and that the role of proposer or responder is randomly changed from round to round. These empathic agents, that displace agents with independent (uncorrelated) offers and proposals, behave far from what is expected rationally, offering and accepting sizable fractions of the amount to be shared. Specific values for the typical offer depend on the details of the interacion network and on the existence of hubs, but they are almost always significantly larger than zero, indicating that the mechanism at work here is quite general and could explain the emergence of empathy in very many different contexts.

Maternal drug use: evaluation of risks to breast-fed infants.

PubMed

Kirksey, A; Groziak, S M

1984-01-01

This paper, based on a review of the literature, evaluates the risks to infants of maternal drug use during lactation. The potential harm of a particular drug to the breastfed infant is related both to the complex mechanism of milk synthesis and secretion and the mode of passage of the drug from plasma into milk. The 1st part of the paper discusses mammary cell and milk synthesis, milk secretion and composition, the mode of passage of drugs into milk, and factors influencing drug concentrations in milk. Drug concentrations in milk are dependent on 6 major factors: drug dosage, proportion bound in plasma, molecular weight, lipid solubility, degree of ionization, and pH difference between plasma and milk. Drugs that are weak acids are ionized to a greater extent and are more protein-bound than weak alkaline drugs. The 2nd part of the paper evaluates the risks to breastfed infants of selected pharmacons. Some categories of drugs that contain pharmacons that should be limited or avoided by nursing mothers are alkylating agents, analgesics and anti-inflammatory agents, anticoagulants, anticonvulsants, anti-infective agents, central nervous system stimulants, hormones, laxatives, minerals, provitamins, psychotherapeutic agents, thyroid affecting agents, and vitamins. The following precautions are suggested to minimize the risks of potentially harmful pharmacons: 1) all unnecessary medications should be avoided by nrusing mothers; 2) if medication is necessary during lactation, drug dosage should be controlled and the infant should be monitored for adverse symptoms; 3) drugs should be administered shortly after breastfeeding and the interval prolonged before the next feeding; and 4) if the infant must be fed soon after a potentially harmful drug has been taken by the mother, bottle feeding is recommended.

An event-triggered control approach for the leader-tracking problem with heterogeneous agents

NASA Astrophysics Data System (ADS)

Garcia, Eloy; Cao, Yongcan; Casbeer, David W.

2018-05-01

This paper presents an event-triggered control and communication framework for the cooperative leader-tracking problem with communication constraints. Continuous communication among agents is not assumed in this work and decentralised event-based strategies are proposed for agents with heterogeneous linear dynamics. Also, the leader dynamics are unknown and only intermittent measurements of its states are obtained by a subset of the followers. The event-based method not only represents a way to restrict communication among agents, but it also provides a decentralised scheme for scheduling information broadcasts. Notably, each agent is able to determine its own broadcasting instants independently of any other agent in the network. In an extension, the case where transmission of information is affected by time-varying communication delays is addressed. Finally, positive lower-bounds on the inter-event time intervals are obtained in order to show that Zeno behaviour does not exist and, therefore, continuous exchange of information is never needed in this framework.

Boron loaded scintillator

DOEpatents

Bell, Zane William [Oak Ridge, TN; Brown, Gilbert Morris [Knoxville, TN; Maya, Leon [Knoxville, TN; Sloop, Jr., Frederick Victor; Sloop, Jr., Frederick Victor [Oak Ridge, TN

2009-10-20

A scintillating composition for detecting neutrons and other radiation comprises a phenyl containing silicone rubber with carborane units and at least one phosphor molecule. The carbonate units can either be a carborane molecule dispersed in the rubber with the aid of a compatibilization agent or can be covalently bound to the silicone.

Deterministic Walks with Choice

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

Beeler, Katy E.; Berenhaut, Kenneth S.; Cooper, Joshua N.

2014-01-10

This paper studies deterministic movement over toroidal grids, integrating local information, bounded memory and choice at individual nodes. The research is motivated by recent work on deterministic random walks, and applications in multi-agent systems. Several results regarding passing tokens through toroidal grids are discussed, as well as some open questions.

Distinguishing rational from irrational applications of pharmacogenetic synergies from the bench to clinical trials.

PubMed

Hucl, Tomas; Gallmeier, Eike; Kern, Scott E

2007-06-01

Single therapeutic agents very often fail in unselected patients. It is therefore commonplace to combine an agent specifically with a selected patient subgroup or with another agent. To support such efforts, it is useful to clarify the distinctions between the terms and the mathematical models used in analyzing combinations. To incorporate molecular disease classifications, the familiar concept of the therapeutic window is modified to define a pharmacogenetic window, which is an unambiguous numerical measure of the magnitude of interaction produced by a combination, and to define a test of pharmacogenetic synergy. In contrast, certain common comparative methods, such as vertical windows (comparing effects at a given dose) and animal models of mutational targets may be dominated by undesirable features. Although this discussion is oriented towards cancer therapy, an extension of these concepts to other comparative biologic assays is feasible and advisable.

Complex adaptive systems and game theory: An unlikely union

USGS Publications Warehouse

Hadzikadic, M.; Carmichael, T.; Curtin, C.

2010-01-01

A Complex Adaptive System is a collection of autonomous, heterogeneous agents, whose behavior is defined with a limited number of rules. A Game Theory is a mathematical construct that assumes a small number of rational players who have a limited number of actions or strategies available to them. The CAS method has the potential to alleviate some of the shortcomings of GT. On the other hand, CAS researchers are always looking for a realistic way to define interactions among agents. GT offers an attractive option for defining the rules of such interactions in a way that is both potentially consistent with observed real-world behavior and subject to mathematical interpretation. This article reports on the results of an effort to build a CAS system that utilizes GT for determining the actions of individual agents. ?? 2009 Wiley Periodicals, Inc. Complexity, 16,24-42, 2010.

From empiricism to rational design: a personal perspective of the evolution of vaccine development.

PubMed

De Gregorio, Ennio; Rappuoli, Rino

2014-07-01

Vaccination, which is the most effective medical intervention that has ever been introduced, originated from the observation that individuals who survived a plague or smallpox would not get the disease twice. To mimic the protective effects of natural infection, Jenner - and later Pasteur - inoculated individuals with attenuated or killed disease-causing agents. This empirical approach inspired a century of vaccine development and the effective prophylaxis of many infectious diseases. From the 1980s, several waves of new technologies have enabled the development of novel vaccines that would not have been possible using the empirical approach. The technological revolution in the field of vaccination is now continuing, and it is delivering novel and safer vaccines. In this Timeline article, we provide our views on the transition from empiricism to rational vaccine design.

Frontiers of finance: evolution and efficient markets.

PubMed

Farmer, J D; Lo, A W

1999-08-31

In this review article, we explore several recent advances in the quantitative modeling of financial markets. We begin with the Efficient Markets Hypothesis and describe how this controversial idea has stimulated a number of new directions of research, some focusing on more elaborate mathematical models that are capable of rationalizing the empirical facts, others taking a completely different tack in rejecting rationality altogether. One of the most promising directions is to view financial markets from a biological perspective and, specifically, within an evolutionary framework in which markets, instruments, institutions, and investors interact and evolve dynamically according to the "law" of economic selection. Under this view, financial agents compete and adapt, but they do not necessarily do so in an optimal fashion. Evolutionary and ecological models of financial markets is truly a new frontier whose exploration has just begun.

A Nonlinear Super-Exponential Rational Model of Speculative Financial Bubbles

NASA Astrophysics Data System (ADS)

Sornette, D.; Andersen, J. V.

Keeping a basic tenet of economic theory, rational expectations, we model the nonlinear positive feedback between agents in the stock market as an interplay between nonlinearity and multiplicative noise. The derived hyperbolic stochastic finite-time singularity formula transforms a Gaussian white noise into a rich time series possessing all the stylized facts of empirical prices, as well as accelerated speculative bubbles preceding crashes. We use the formula to invert the two years of price history prior to the recent crash on the Nasdaq (April 2000) and prior to the crash in the Hong Kong market associated with the Asian crisis in early 1994. These complex price dynamics are captured using only one exponent controlling the explosion, the variance and mean of the underlying random walk. This offers a new and powerful detection tool of speculative bubbles and herding behavior.

Frontiers of finance: Evolution and efficient markets

PubMed Central

Farmer, J. Doyne; Lo, Andrew W.

1999-01-01

In this review article, we explore several recent advances in the quantitative modeling of financial markets. We begin with the Efficient Markets Hypothesis and describe how this controversial idea has stimulated a number of new directions of research, some focusing on more elaborate mathematical models that are capable of rationalizing the empirical facts, others taking a completely different tack in rejecting rationality altogether. One of the most promising directions is to view financial markets from a biological perspective and, specifically, within an evolutionary framework in which markets, instruments, institutions, and investors interact and evolve dynamically according to the “law” of economic selection. Under this view, financial agents compete and adapt, but they do not necessarily do so in an optimal fashion. Evolutionary and ecological models of financial markets is truly a new frontier whose exploration has just begun. PMID:10468547

Mitochondrial rhodanese: membrane-bound and complexed activity.

PubMed

Ogata, K; Volini, M

1990-05-15

We have proposed that phosphorylated and dephosphorylated forms of the mitochondrial sulfurtransferase, rhodanese, function as converter enzymes that interact with membrane-bound iron-sulfur centers of the electron transport chain to modulate the rate of mitochondrial respiration (Ogata, K., Dai, X., and Volini, M. (1989) J. Biol. Chem. 204, 2718-2725). In the present studies, we have explored some structural aspects of the mitochondrial rhodanese system. By sequential extraction of lysed mitochondria with phosphate buffer and phosphate buffer containing 20 mM cholate, we have shown that 30% of the rhodanese activity of bovine liver is membrane-bound. Resolution of cholate extracts on Sephadex G-100 indicates that part of the bound rhodanese is complexed with other mitochondrial proteins. Tests with the complex show that it forms iron-sulfur centers when incubated with the rhodanese sulfur-donor substrate thiosulfate, iron ions, and a reducing agent. Experiments on the rhodanese activity of rat liver mitochondria give similar results. Taken together, the findings indicate that liver rhodanese is in part bound to the mitochondrial membrane as a component of a multiprotein complex that forms iron-sulfur centers. The findings are consistent with the role we propose for rhodanese in the modulation of mitochondrial respiratory activity.

Quantitative detection of pathogens in centrifugal microfluidic disks

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

Koh, Chung-Yan; Schaff, Ulrich Y.; Sommer, Gregory Jon

A system and methods for detection of a nucleic acid including forming a plurality of nucleic acid detection complexes are described, each of the complexes including a nucleic acid analyte, a detection agent and a functionalized probe. The method further including binding the nucleic acid detection complexes to a plurality of functionalized particles in a fluid sample and separating the functionalized particles having the nucleic acid detection complexes bound thereto from the fluid sample using a density media. The nucleic acid analyte is detected by detecting the detection agent.

Biosensor platform based on carbon nanotubes covalently modified with aptamers

NASA Astrophysics Data System (ADS)

Komarov, I. A.; Rubtsova, E. I.; Golovin, A. V.; Bobrinetskiy, I. I.

2016-12-01

We developed a new platform for biosensing applications. Aptamers as sensitive agents have a great potential and gives us possibility to have highest possible selectivity among other sensing agents like enzymes or antibodies. We covalently bound aptamers to the functional groups of c-CNTs and then put this system on the surface of polymer substrate. Thus we got high sensitive flexible transparent biological sensors. We also suggest that by varying aptamer type we can make set of biosensors for disease detection which can be integrated into self-healthcare systems and gadgets.

para-Sulfonatocalix[4]arene and polyamidoamine dendrimer nanocomplexes as delivery vehicles for a novel platinum anticancer agent.

PubMed

Pang, Chi Ting; Ammit, Alaina J; Ong, Yu Qing Elysia; Wheate, Nial J

2017-11-01

Novel para-sulfonatocalix[4]arene (sCX[4]) and polyamidoamine (PAMAM) dendrimer nanocomplexes were evaluated as delivery vehicles for the platinum anticancer agent [(1,10-phenanthroline)(1S,2S-diaminocyclohexane)platinum(II)] chloride (PHENSS). Different ratios of sCX[4] to PHENSS were tested for their compatibility, with a ratio of 6:1 sCX[4]:PHENSS having the best solubility. The loading of sCX[4], and sCX[4]-bound PHENSS, onto three different generations of PAMAM dendrimers (G3.0-5.0) was examined using UV-visible spectrophotometry. The quantity of sCX[4] bound was found to increase exponentially with dendrimer size: G3, 15 sCX[4] molecules per dendrimer; G4, 37; and G5, 78. Similarly, the loading of sCX[4]-bound PHENSS also increased with increasing dendrimer size: G3, 7 PHENSS molecules per dendrimer; G4, 14; and G5, 28.5. The loading of sCX[4]-bound PHENSS molecules is significantly lower when compared with that of sCX[4], which indicates that less than half of the binding sites were occupied (45, 44, and 44%, respectively). By 1 H NMR and UV-vis analysis, the nanocomplex was found to be stable in NaCl solutions at concentrations up to 150mM. While PHENSS is more active in vitro than cisplatin against the human breast cancer cell line, MCF-7, delivery of PHENSS using the sCX[4]-dendrimer nanocomplexes, regardless of dendrimer generation, had little effect on PHENSS cytotoxicity. The results of this study may have application in the delivery of a variety of small molecule metal-based drugs for which chemical conjugation to a nanoparticle is undesired or not feasible. Copyright © 2017 Elsevier Inc. All rights reserved.

Structural rearrangements occurring upon cofactor binding in the Mycobacterium smegmatis β-ketoacyl-acyl carrier protein reductase MabA.

PubMed

Küssau, Tanja; Flipo, Marion; Van Wyk, Niel; Viljoen, Albertus; Olieric, Vincent; Kremer, Laurent; Blaise, Mickaël

2018-05-01

In mycobacteria, the ketoacyl-acyl carrier protein (ACP) reductase MabA (designated FabG in other bacteria) catalyzes the NADPH-dependent reduction of β-ketoacyl-ACP substrates to β-hydroxyacyl-ACP products. This first reductive step in the fatty-acid biosynthesis elongation cycle is essential for bacteria, which makes MabA/FabG an interesting drug target. To date, however, very few molecules targeting FabG have been discovered and MabA remains the only enzyme of the mycobacterial type II fatty-acid synthase that lacks specific inhibitors. Despite the existence of several MabA/FabG crystal structures, the structural rearrangement that occurs upon cofactor binding is still not fully understood. Therefore, unlocking this knowledge gap could help in the design of new inhibitors. Here, high-resolution crystal structures of MabA from Mycobacterium smegmatis in its apo, NADP + -bound and NADPH-bound forms are reported. Comparison of these crystal structures reveals the structural reorganization of the lid region covering the active site of the enzyme. The crystal structure of the apo form revealed numerous residues that trigger steric hindrance to the binding of NADPH and substrate. Upon NADPH binding, these residues are pushed away from the active site, allowing the enzyme to adopt an open conformation. The transition from an NADPH-bound to an NADP + -bound form is likely to facilitate release of the product. These results may be useful for subsequent rational drug design and/or for in silico drug-screening approaches targeting MabA/FabG.

Computer-Aided Structure Based Drug Design Approaches for the Discovery of New Anti-CHIKV Agents.

PubMed

Jadav, Surender Singh; Sinha, Barij Nayan; Hilgenfeld, Rolf; Jayaprakash, Venkatesan

2017-11-10

Chikungunya is a viral infection caused by Chikungunya virus (CHIKV), an arbovirus transmitted through mosquito (Aedes aegypti and Aedes albopictus) bite. The virus from sylvatic cycle in Africa mutated to new vector adaptation and became one of the major emerging and re-emerging viral infections in the past decade, affecting more than 40 countries. Efforts are being made by many researches to develop means to prevent and control the infection through vaccines and vector control strategy. On the other hand, search for novel chemotherapeutic agents for the treatment of infected patients is on. Approach of repurposed drug is one way of identifying an existing drug for the treatment of CHIKV infection. Review the history of CHIKV nsp2 protease inhibitors derived through structure-based computer-aided drug design along with phytochemicals identified as anti-CHIKV agents. A survey on CHIKV inhibitors reported till date has been carriedout. The data obtained were organized and discussed under natural substances and synthetic derivatives obtained as result of rational design. The review provides a well organized content in chronological order that has highly significant information for medicinal chemist who wish to explore the area of Anti-CHIKV drug design and development. Natural compounds with different scaffolds provides an opportunity to explore Ligand based drug design (LBDD), while rational drug design approaches provides opportunity to explore the Structure based drug design. From the presented mini-review, readers can understand that this area is less explored and has lots of potential in anti-CHIKVviral drug design & development. of reported literature inferred that, unlike other viral proteases, the nsP2 protease can be targeted for CHIKV viral inhibition. The HTVS process for the identification of anti-CHIK agents provided a few successive validated lead compounds against CHIKV infections. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Universal Trade-Off between Power, Efficiency, and Constancy in Steady-State Heat Engines

NASA Astrophysics Data System (ADS)

Pietzonka, Patrick; Seifert, Udo

2018-05-01

Heat engines should ideally have large power output, operate close to Carnot efficiency and show constancy, i.e., exhibit only small fluctuations in this output. For steady-state heat engines, driven by a constant temperature difference between the two heat baths, we prove that out of these three requirements only two are compatible. Constancy enters quantitatively the conventional trade-off between power and efficiency. Thus, we rationalize and unify recent suggestions for overcoming this simple trade-off. Our universal bound is illustrated for a paradigmatic model of a quantum dot solar cell and for a Brownian gyrator delivering mechanical work against an external force.

Teaching about Impulse and Momentum

ERIC Educational Resources Information Center

Franklin, Bill

2004-01-01

This American Association of Physics Teachers/Physics Teaching Resource Agents (APPT/PTRA) spiral-bound manual features labs and demos physics teachers can use to give students hands-on opportunities to learn about impulse and momentum. "Make-and-take activities" include AAPT Apparatus Contest winners "An Air Impulse Rocket," "A Fan Driven…

16 CFR 1304.3 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS BAN OF... definitions in section 3 of the Consumer Product Safety Act (15 U.S.C. 2052) apply to this part 1304. (b... that which is not bound, or otherwise “locked-in” to a product by resins or other bonding agents, or...

Retrospective survey of the efficacy of mandatory implementation of the Essential Medicine Policy in the primary healthcare setting in China: failure to promote the rational use of antibiotics in clinics.

PubMed

Xiao, Yonghong; Wang, Jin; Shen, Ping; Zheng, Beiwen; Zheng, Yingdong; Li, Lanjuan

2016-10-01

The objective of this study was to understand the impact of implementation of the Essential Medicine Policy (EMP) on the rational use of antibiotics in primary medical institutions in China. A retrospective survey was conducted in 39 primary medical institutions to compare the efficacy of EMP in rational antibiotic use. All institutions completed the survey 1 year before and 1 year after implementation of the EMP. In particular, antibiotic use and its rationality were closely examined. The institutions mainly dealt with common diseases, especially non-infectious chronic diseases. Antibiotic usage was very inappropriate both before and after EMP implementation. Before and after EMP implementation, respectively, the median outpatient cost was US$6.34 and US$5.05, 52.50% (2005/3819) and 53.41% (1865/3492) of the outpatient prescriptions contained antibiotics, and 76.23% (1132/1485) and 78.83% (1106/1403) of inpatients were administered antibiotics. In addition, 98.38% (425/432) and 97.52% (512/525) of surgical inpatients were administered antibiotics, respectively, and 80.76% (638/790) and 75.19% (503/669) of patients with a cold were prescribed antibiotics, respectively. The most commonly used antibiotics were broad-spectrum and injectable agents, including cephalosporins, fluoroquinolones and penicillins. This profile showed little change following implementation of the EMP. In conclusion, inappropriate antibiotic use is a serious problem in primary medical institutions in China. Whilst enforcing the EMP reduced the cost of medical services, it had little effect on promoting the rational use of antibiotics. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Design of a small molecule against an oncogenic noncoding RNA

PubMed Central

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

2016-01-01

The design of precision, preclinical therapeutics from sequence is difficult, but advances in this area, particularly those focused on rational design, could quickly transform the sequence of disease-causing gene products into lead modalities. Herein, we describe the use of Inforna, a computational approach that enables the rational design of small molecules targeting RNA to quickly provide a potent modulator of oncogenic microRNA-96 (miR-96). We mined the secondary structure of primary microRNA-96 (pri-miR-96) hairpin precursor against a database of RNA motif–small molecule interactions, which identified modules that bound RNA motifs nearby and in the Drosha processing site. Precise linking of these modules together provided Targaprimir-96 (3), which selectively modulates miR-96 production in cancer cells and triggers apoptosis. Importantly, the compound is ineffective on healthy breast cells, and exogenous overexpression of pri-miR-96 reduced compound potency in breast cancer cells. Chemical Cross-Linking and Isolation by Pull-Down (Chem-CLIP), a small-molecule RNA target validation approach, shows that 3 directly engages pri-miR-96 in breast cancer cells. In vivo, 3 has a favorable pharmacokinetic profile and decreases tumor burden in a mouse model of triple-negative breast cancer. Thus, rational design can quickly produce precision, in vivo bioactive lead small molecules against hard-to-treat cancers by targeting oncogenic noncoding RNAs, advancing a disease-to-gene-to-drug paradigm. PMID:27170187

The nonlinear aeroelastic characteristics of a folding wing with cubic stiffness

NASA Astrophysics Data System (ADS)

Hu, Wei; Yang, Zhichun; Gu, Yingsong; Wang, Xiaochen

2017-07-01

This paper focuses on the nonlinear aeroelastic characteristics of a folding wing in the quasi-steady condition (namely at fixed folding angles) and during the morphing process. The structure model of the folding wing is formulated by the Lagrange equations, and the constraint equation is used to describe the morphing strategy. The aerodynamic influence coefficient matrices at several folding angles are calculated by the Doublet Lattice method, and described as rational functions in the Laplace domain by the rational function approximation, and then the Kriging agent model technique is adopted to interpolate the coefficient matrices of the rational functions, and the aerodynamics model of the folding wing during the morphing process is built. The aeroelastic responses of the folding wing with cubic stiffness are simulated, and the results show that the motion types of aeroelastic responses in the quasi-steady condition and during the morphing process are all sensitive to the initial condition and folding angle. During the morphing process, the transition of the motion types is observed. And apart from the period of transition, the aeroelastic response at some folding angles may exhibit different motion types, which can be found from the results in the quasi-steady condition.

Successful implementation of a guideline program for the rational use of lipid-lowering drugs.

PubMed

Stuart, M E; Handley, M A; Chamberlain, M A; Wallach, R W; Penna, P M; Stergachis, A

1991-01-01

Following the National Cholesterol Educational Program's (NCEP) 1988 screening and treatment recommendations, an educational and behavior-change program at Group Health Cooperative of Puget Sound (GHC) was developed to guide the use of lipid-lowering drugs within the larger context of cardiac risk reduction. The program has been successful in advancing a rational program to enhance care and manage costs of the use of lipid-lowering agents at GHC. Cost savings have been significant over the past two years. The educational design of the program includes training and ongoing education of a core group of "lipid gurus," who educate colleagues in area medical centers in a rational approach to hyperlipidemia. Patient education and patient participation in decision-making was emphasized. Program evaluation has demonstrated that physicians and patients are satisfied with the program, and inappropriate drug expenditures have been prevented. Key elements of the program include a critical review of outcome studies in the medical literature, use of information systems, algorithms and written materials organized into a well-designed, ongoing educational program, and development of a core group of physicians and pharmacists to administer the program at the clinic level.

Operation Desert Shield Lessons Learned

DTIC Science & Technology

1991-01-01

MRE, T and B rations) issued in Army Mess Halls. (2) Peelable fruits, i.e., oranges and bananas , apples, and pears after being peeled and washed...every day, they cannot get a good seal on their protective masks and are likely to become casualties in the event of a chemical attack. LESSON...liquid mustard agent is imminent. (2) Find clean areas to get relief from wearing rubber gloves and boots before softening of the hands and feet

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

Barta, Michael L.; Skaff, D. Andrew; McWhorter, William J.

The polyisoprenoid compound undecaprenyl phosphate is required for biosynthesis of cell wall peptidoglycans in Gram-positive bacteria, including pathogenic Enterococcus, Streptococcus, and Staphylococcus spp. In these organisms, the mevalonate pathway is used to produce the precursor isoprenoid, isopentenyl 5-diphosphate. Mevalonate diphosphate decarboxylase (MDD) catalyzes formation of isopentenyl 5-diphosphate in an ATP-dependent irreversible reaction and is therefore an attractive target for inhibitor development that could lead to new antimicrobial agents. To facilitate exploration of this possibility, we report the crystal structure of Staphylococcus epidermidis MDD (1.85 {angstrom} resolution) and, to the best of our knowledge, the first structures of liganded MDD. Thesemore » structures include MDD bound to the mevalonate 5-diphosphate analogs diphosphoglycolyl proline (2.05 {angstrom} resolution) and 6-fluoromevalonate diphosphate (FMVAPP; 2.2 {angstrom} resolution). Comparison of these structures provides a physical basis for the significant differences in K{sub i} values observed for these inhibitors. Inspection of enzyme/inhibitor structures identified the side chain of invariant Ser{sup 192} as making potential contributions to catalysis. Significantly, Ser {yields} Ala substitution of this side chain decreases k{sub cat} by {approx}10{sup 3}-fold, even though binding interactions between FMVAPP and this mutant are similar to those observed with wild type MDD, as judged by the 2.1 {angstrom} cocrystal structure of S192A with FMVAPP. Comparison of microbial MDD structures with those of mammalian counterparts reveals potential targets at the active site periphery that may be exploited to selectively target the microbial enzymes. These studies provide a structural basis for previous observations regarding the MDD mechanism and inform future work toward rational inhibitor design.« less

Complementary proteomic approaches reveal mitochondrial dysfunction, immune and inflammatory dysregulation in a mouse model of Gulf War Illness.

PubMed

Zakirova, Zuchra; Reed, Jon; Crynen, Gogce; Horne, Lauren; Hassan, Samira; Mathura, Venkatarajan; Mullan, Michael; Crawford, Fiona; Ait-Ghezala, Ghania

2017-09-01

Long-term consequences of combined pyridostigmine bromide (PB) and permethrin (PER) exposure in C57BL6/J mice using a well-characterized mouse model of exposure to these Gulf War (GW) agents were explored at the protein level. We used orthogonal proteomic approaches to identify pathways that are chronically impacted in the mouse CNS due to semiacute GW agent exposure early in life. These analyses were performed on soluble and membrane-bound protein fractions from brain samples using two orthogonal isotopic labeling LC-MS/MS proteomic approaches-stable isotope dimethyl labeling and iTRAQ. The use of these approaches allowed for greater coverage of proteins than was possible by either one alone and revealed both distinct and overlapping datasets. This combined analysis identified changes in several mitochondrial, as well as immune and inflammatory pathways after GW agent exposure. The work discussed here provides insight into GW agent exposure dependent mechanisms that adversely affect mitochondrial function and immune and inflammatory regulation. Collectively, our work identified key pathways which were chronically impacted in the mouse CNS following acute GW agent exposure, this may lead to the identification of potential targets for therapeutic intervention in the future. Long-term consequences of combined PB and PER exposure in C57BL6/J mice using a well-characterized mouse model of exposure to these GW agents were explored at the protein level. Expanding on earlier work, we used orthogonal proteomic approaches to identify pathways that are chronically impacted in the mouse CNS due to semiacute GW agent exposure early in life. These analyses were performed on soluble and membrane-bound protein fractions from brain samples using two orthogonal isotopic labeling LC-MS/MS proteomic approaches-stable isotope dimethyl labeling and iTRAQ. The use of these approaches allowed for greater coverage of proteins than was possible by either one alone and revealed both distinct and overlapping datasets. This combined analysis identified changes in several mitochondrial, as well as immune and inflammatory pathways after GW agent exposure. The work discussed here provides insight into GW agent exposure dependent mechanisms that adversely affect mitochondrial function and immune and inflammatory regulation at 5 months postexposure to PB + PER. © 2017 The Authors. PROTEOMICS - Clinical Applications published by WILEY-VCH Verlag GmbH & Co. KGaA.

Complementary proteomic approaches reveal mitochondrial dysfunction, immune and inflammatory dysregulation in a mouse model of Gulf War Illness

PubMed Central

Zakirova, Zuchra; Reed, Jon; Crynen, Gogce; Horne, Lauren; Hassan, Samira; Mathura, Venkatarajan; Mullan, Michael; Crawford, Fiona

2017-01-01

Purpose Long‐term consequences of combined pyridostigmine bromide (PB) and permethrin (PER) exposure in C57BL6/J mice using a well‐characterized mouse model of exposure to these Gulf War (GW) agents were explored at the protein level. Experimental design We used orthogonal proteomic approaches to identify pathways that are chronically impacted in the mouse CNS due to semiacute GW agent exposure early in life. These analyses were performed on soluble and membrane‐bound protein fractions from brain samples using two orthogonal isotopic labeling LC‐MS/MS proteomic approaches—stable isotope dimethyl labeling and iTRAQ. Results The use of these approaches allowed for greater coverage of proteins than was possible by either one alone and revealed both distinct and overlapping datasets. This combined analysis identified changes in several mitochondrial, as well as immune and inflammatory pathways after GW agent exposure. Conclusions and clinical relevance The work discussed here provides insight into GW agent exposure dependent mechanisms that adversely affect mitochondrial function and immune and inflammatory regulation. Collectively, our work identified key pathways which were chronically impacted in the mouse CNS following acute GW agent exposure, this may lead to the identification of potential targets for therapeutic intervention in the future. Long‐term consequences of combined PB and PER exposure in C57BL6/J mice using a well‐characterized mouse model of exposure to these GW agents were explored at the protein level. Expanding on earlier work, we used orthogonal proteomic approaches to identify pathways that are chronically impacted in the mouse CNS due to semiacute GW agent exposure early in life. These analyses were performed on soluble and membrane‐bound protein fractions from brain samples using two orthogonal isotopic labeling LC‐MS/MS proteomic approaches—stable isotope dimethyl labeling and iTRAQ. The use of these approaches allowed for greater coverage of proteins than was possible by either one alone and revealed both distinct and overlapping datasets. This combined analysis identified changes in several mitochondrial, as well as immune and inflammatory pathways after GW agent exposure. The work discussed here provides insight into GW agent exposure dependent mechanisms that adversely affect mitochondrial function and immune and inflammatory regulation at 5 months postexposure to PB + PER. PMID:28371386

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

Prescribed performance distributed consensus control for nonlinear multi-agent systems with unknown dead-zone input

NASA Astrophysics Data System (ADS)

Cui, Guozeng; Xu, Shengyuan; Ma, Qian; Li, Yongmin; Zhang, Zhengqiang

2018-05-01

In this paper, the problem of prescribed performance distributed output consensus for higher-order non-affine nonlinear multi-agent systems with unknown dead-zone input is investigated. Fuzzy logical systems are utilised to identify the unknown nonlinearities. By introducing prescribed performance, the transient and steady performance of synchronisation errors are guaranteed. Based on Lyapunov stability theory and the dynamic surface control technique, a new distributed consensus algorithm for non-affine nonlinear multi-agent systems is proposed, which ensures cooperatively uniformly ultimately boundedness of all signals in the closed-loop systems and enables the output of each follower to synchronise with the leader within predefined bounded error. Finally, simulation examples are provided to demonstrate the effectiveness of the proposed control scheme.

Spin-Center Shift-Enabled Direct Enantioselective α-Benzylation of Aldehydes with Alcohols.

PubMed

Nacsa, Eric D; MacMillan, David W C

2018-03-07

Nature routinely engages alcohols as leaving groups, as DNA biosynthesis relies on the removal of water from ribonucleoside diphosphates by a radical-mediated "spin-center shift" (SCS) mechanism. Alcohols, however, remain underused as alkylating agents in synthetic chemistry due to their low reactivity in two-electron pathways. We report herein an enantioselective α-benzylation of aldehydes using alcohols as alkylating agents based on the mechanistic principle of spin-center shift. This strategy harnesses the dual activation modes of photoredox and organocatalysis, engaging the alcohol by SCS and capturing the resulting benzylic radical with a catalytically generated enamine. Mechanistic studies provide evidence for SCS as a key elementary step, identify the origins of competing reactions, and enable improvements in chemoselectivity by rational photocatalyst design.

>From naive to sophisticated behavior in multiagents-based financial market models

NASA Astrophysics Data System (ADS)

Mansilla, R.

2000-09-01

The behavior of physical complexity and mutual information function of the outcome of a model of heterogeneous, inductive rational agents inspired by the El Farol Bar problem and the Minority Game is studied. The first magnitude is a measure rooted in the Kolmogorov-Chaitin theory and the second a measure related to Shannon's information entropy. Extensive computer simulations were done, as a result of which, is proposed an ansatz for physical complexity of the type C(l)=lα and the dependence of the exponent α from the parameters of the model is established. The accuracy of our results and the relationship with the behavior of mutual information function as a measure of time correlation of agents choice are discussed.

Heterocyclic N-Oxides – An Emerging Class of Therapeutic Agents

PubMed Central

Mfuh, Adelphe M.; Larionov, Oleg V.

2016-01-01

Heterocyclic N-oxides have emerged as potent compounds with anticancer, antibacterial, antihypertensive, antiparasitic, anti-HIV, anti-inflammatory, herbicidal, neuroprotective, and procognitive activities. The N-oxide motif has been successfully employed in a number of recent drug development projects. This review surveys the emergence of this scaffold in the mainstream medicinal chemistry with a focus on the discovery of the heterocyclic N-oxide drugs, N-oxide-specific mechanisms of action, drug-receptor interactions and synthetic avenues to these compounds. As the first review on this subject that covers the developments since 1950s to date, it is expected that it will inspire wider implementation of the heterocyclic N-oxide motif in the rational design of new medicinal agents. PMID:26087764

Action comprehension in non-human primates: motor simulation or inferential reasoning?

PubMed

Wood, Justin N; Hauser, Marc D

2008-12-01

Some argue that action comprehension is intimately connected with the observer's own motor capacities, whereas others argue that action comprehension depends on non-motor inferential mechanisms. We address this debate by reviewing comparative studies that license four conclusions: monkeys and apes extract the meaning of an action (i) by going beyond the surface properties of actions, attributing goals and intentions to the agent; (ii) by using environmental information to infer when actions are rational; (iii) by making predictions about an agent's goal, and the most probable action to obtain the goal given environmental constraints; (iv) in situations in which they are physiologically incapable of producing the actions. Motor theories are, thus, insufficient to account for primate action comprehension in the absence of inferential mechanisms.

US neurologists: attitudes on rationing.

PubMed

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

2000-11-28

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

Artificial intelligence and the future.

PubMed

Clocksin, William F

2003-08-15

We consider some of the ideas influencing current artificial-intelligence research and outline an alternative conceptual framework that gives priority to social relationships as a key component and constructor of intelligent behaviour. The framework starts from Weizenbaum's observation that intelligence manifests itself only relative to specific social and cultural contexts. This is in contrast to a prevailing view, which sees intelligence as an abstract capability of the individual mind based on a mechanism for rational thought. The new approach is not based on the conventional idea that the mind is a rational processor of symbolic information, nor does it require the idea that thought is a kind of abstract problem solving with a semantics that is independent of its embodiment. Instead, priority is given to affective and social responses that serve to engage the whole agent in the life of the communities in which it participates. Intelligence is seen not as the deployment of capabilities for problem solving, but as constructed by the continual, ever-changing and unfinished engagement with the social group within the environment. The construction of the identity of the intelligent agent involves the appropriation or 'taking up' of positions within the conversations and narratives in which it participates. Thus, the new approach argues that the intelligent agent is shaped by the meaning ascribed to experience, by its situation in the social matrix, and by practices of self and of relationship into which intelligent life is recruited. This has implications for the technology of the future, as, for example, classic artificial intelligence models such as goal-directed problem solving are seen as special cases of narrative practices instead of as ontological foundations.

Agent-based modelling of consumer energy choices

NASA Astrophysics Data System (ADS)

Rai, Varun; Henry, Adam Douglas

2016-06-01

Strategies to mitigate global climate change should be grounded in a rigorous understanding of energy systems, particularly the factors that drive energy demand. Agent-based modelling (ABM) is a powerful tool for representing the complexities of energy demand, such as social interactions and spatial constraints. Unlike other approaches for modelling energy demand, ABM is not limited to studying perfectly rational agents or to abstracting micro details into system-level equations. Instead, ABM provides the ability to represent behaviours of energy consumers -- such as individual households -- using a range of theories, and to examine how the interaction of heterogeneous agents at the micro-level produces macro outcomes of importance to the global climate, such as the adoption of low-carbon behaviours and technologies over space and time. We provide an overview of ABM work in the area of consumer energy choices, with a focus on identifying specific ways in which ABM can improve understanding of both fundamental scientific and applied aspects of the demand side of energy to aid the design of better policies and programmes. Future research needs for improving the practice of ABM to better understand energy demand are also discussed.

Substantiation of International Nanomaterials Security Group Creation

NASA Astrophysics Data System (ADS)

Sosnov, A.; Sadovnikov, S.; Panfilov, S.; Magarshak, Yu.

Nanotechnology has achieved the status as one of the critical R&D area. Scientists use the unique properties of atomic and molecular assemblages built at the nanometer scale. The ability to manipulate the physical, chemical, and biological properties of molecules and particles affords to design agents with set up properties. But the technology allows creating not only useful agents. Possible accidental or deliberate creation of new nanoparticles (NPs) with dangerous properties is highly probable minor product of progress in the new area. The article briefly describes some pathways in development and implementation of NPs for medicinal and the similar purposes. Some of NPs can effective facilitate and mask transport of various agents in various environments. Possible creation of new dangerous NPs (e.g. conjugates based on combination of extensively use NPs and chemical, biological and radioactive agents) as well as creation of brand new NPs and nanodevices with unique properties needs creation of international multidiscipline community for security evaluation of nanomaterials and technologies. The community will forecast possible dangerous unexpectedness in the field of nanoscale materials and devices and suggests rational pathways for prevention of the threats.

In Situ Probes of Capture and Decomposition of Chemical Warfare Agent Simulants by Zr-Based Metal Organic Frameworks

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

Plonka, Anna M.; Wang, Qi; Gordon, Wesley O.

Recently, Zr-based metal organic frameworks (MOFs) were shown to be among the fastest catalysts of nerve-agent hydrolysis in solution. Here, we report a detailed study of the adsorption and decomposition of a nerve-agent simulant, dimethyl methylphosphonate (DMMP), on UiO-66, UiO-67, MOF-808, and NU-1000 using synchrotron-based X-ray powder diffraction, X-ray absorption, and infrared spectroscopy, which reveals key aspects of the reaction mechanism. The diffraction measurements indicate that all four MOFs adsorb DMMP (introduced at atmospheric pressures through a flow of helium or air) within the pore space. In addition, the combination of X-ray absorption and infrared spectra suggests direct coordination ofmore » DMMP to the Zr6 cores of all MOFs, which ultimately leads to decomposition to phosphonate products. Our experimental probes into the mechanism of adsorption and decomposition of chemical warfare agent simulants on Zr-based MOFs open new opportunities in rational design of new and superior decontamination materials.« less

In Situ Probes of Capture and Decomposition of Chemical Warfare Agent Simulants by Zr-Based Metal Organic Frameworks

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

Plonka, Anna M.; Wang, Qi; Gordon, Wesley O.

Zr-based metal organic frameworks (MOFs) have been recently shown to be among the fastest catalysts of nerve-agent hydrolysis in solution. We report a detailed study of the adsorption and decomposition of a nerve-agent simulant, dimethyl methylphosphonate (DMMP), on UiO-66, UiO-67, MOF-808, and NU-1000 using synchrotron-based X-ray powder diffraction, X-ray absorption, and infrared spectroscopy, which reveals key aspects of the reaction mechanism. The diffraction measurements indicate that all four MOFs adsorb DMMP (introduced at atmospheric pressures through a flow of helium or air) within the pore space. In addition, the combination of X-ray absorption and infrared spectra suggests direct coordination ofmore » DMMP to the Zr6 cores of all MOFs, which ultimately leads to decomposition to phosphonate products. These experimental probes into the mechanism of adsorption and decomposition of chemical warfare agent simulants on Zr-based MOFs open new opportunities in rational design of new and superior decontamination materials.« less

Agent Communication for Dynamic Belief Update

NASA Astrophysics Data System (ADS)

Kobayashi, Mikito; Tojo, Satoshi

Thus far, various formalizations of rational / logical agent model have been proposed. In this paper, we include the notion of communication channel and belief modality into update logic, and introduce Belief Update Logic (BUL). First, we discuss that how we can reformalize the inform action of FIPA-ACL into communication channel, which represents a connection between agents. Thus, our agents can send a message only when they believe, and also there actually is, a channel between him / her and a receiver. Then, we present a static belief logic (BL) and show its soundness and completeness. Next, we develop the logic to BUL, which can update Kripke model by the inform action; in which we show that in the updated model the belief operator also satisfies K45. Thereafter, we show that every sentence in BUL can be translated into BL; thus, we can contend that BUL is also sound and complete. Furthermore, we discuss the features of CUL, including the case of inconsistent information, as well as channel transmission. Finally, we summarize our contribution and discuss some future issues.

In Situ Probes of Capture and Decomposition of Chemical Warfare Agent Simulants by Zr-Based Metal Organic Frameworks

DOE PAGES

Plonka, Anna M.; Wang, Qi; Gordon, Wesley O.; ...

2016-12-30

Recently, Zr-based metal organic frameworks (MOFs) were shown to be among the fastest catalysts of nerve-agent hydrolysis in solution. Here, we report a detailed study of the adsorption and decomposition of a nerve-agent simulant, dimethyl methylphosphonate (DMMP), on UiO-66, UiO-67, MOF-808, and NU-1000 using synchrotron-based X-ray powder diffraction, X-ray absorption, and infrared spectroscopy, which reveals key aspects of the reaction mechanism. The diffraction measurements indicate that all four MOFs adsorb DMMP (introduced at atmospheric pressures through a flow of helium or air) within the pore space. In addition, the combination of X-ray absorption and infrared spectra suggests direct coordination ofmore » DMMP to the Zr6 cores of all MOFs, which ultimately leads to decomposition to phosphonate products. Our experimental probes into the mechanism of adsorption and decomposition of chemical warfare agent simulants on Zr-based MOFs open new opportunities in rational design of new and superior decontamination materials.« less

Inner conflict in patients receiving oral anticancer agents: a qualitative study.

PubMed

Yagasaki, Kaori; Komatsu, Hiroko; Takahashi, Tsunehiro

2015-04-14

To explore the experiences of patients receiving oral anticancer agents. A qualitative study using semistructured interviews with a grounded theory approach. A university hospital in Japan. 14 patients with gastric cancer who managed their cancer with oral anticancer agents. Patients with cancer experienced inner conflict between rational belief and emotional resistance to taking medication due to confrontation with cancer, doubt regarding efficacy and concerns over potential harm attached to use of the agent. Although they perceived themselves as being adherent to medication, they reported partial non-adherent behaviours. The patients reassessed their lives through the experience of inner conflict and, ultimately, they recognised their role in medication therapy. Patients with cancer experienced inner conflict, in which considerable emotional resistance to taking their medication affected their occasional non-adherent behaviours. In patient-centred care, it is imperative that healthcare providers understand patients' inner conflict and inconsistency between their subjective view and behaviour to support patient adherence. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Bacterial Transcription as a Target for Antibacterial Drug Development

PubMed Central

Ma, Cong; Yang, Xiao

2016-01-01

SUMMARY Transcription, the first step of gene expression, is carried out by the enzyme RNA polymerase (RNAP) and is regulated through interaction with a series of protein transcription factors. RNAP and its associated transcription factors are highly conserved across the bacterial domain and represent excellent targets for broad-spectrum antibacterial agent discovery. Despite the numerous antibiotics on the market, there are only two series currently approved that target transcription. The determination of the three-dimensional structures of RNAP and transcription complexes at high resolution over the last 15 years has led to renewed interest in targeting this essential process for antibiotic development by utilizing rational structure-based approaches. In this review, we describe the inhibition of the bacterial transcription process with respect to structural studies of RNAP, highlight recent progress toward the discovery of novel transcription inhibitors, and suggest additional potential antibacterial targets for rational drug design. PMID:26764017

Structural basis of GSK-3 inhibition by N-terminal phosphorylation and by the Wnt receptor LRP6.

PubMed

Stamos, Jennifer L; Chu, Matthew Ling-Hon; Enos, Michael D; Shah, Niket; Weis, William I

2014-03-18

Glycogen synthase kinase-3 (GSK-3) is a key regulator of many cellular signaling pathways. Unlike most kinases, GSK-3 is controlled by inhibition rather than by specific activation. In the insulin and several other signaling pathways, phosphorylation of a serine present in a conserved sequence near the amino terminus of GSK-3 generates an auto-inhibitory peptide. In contrast, Wnt/β-catenin signal transduction requires phosphorylation of Ser/Pro rich sequences present in the Wnt co-receptors LRP5/6, and these motifs inhibit GSK-3 activity. We present crystal structures of GSK-3 bound to its phosphorylated N-terminus and to two of the phosphorylated LRP6 motifs. A conserved loop unique to GSK-3 undergoes a dramatic conformational change that clamps the bound pseudo-substrate peptides, and reveals the mechanism of primed substrate recognition. The structures rationalize target sequence preferences and suggest avenues for the design of inhibitors selective for a subset of pathways regulated by GSK-3. DOI: http://dx.doi.org/10.7554/eLife.01998.001.

Bound on the Slope of Steady Water Waves with Favorable Vorticity

NASA Astrophysics Data System (ADS)

Strauss, Walter A.; Wheeler, Miles H.

2016-12-01

We consider the angle {θ} of inclination (with respect to the horizontal) of the profile of a steady two dimensional inviscid symmetric periodic or solitary water wave subject to gravity. Although {θ} may surpass 30° for some irrotational waves close to the extreme wave, Amick (Arch Ration Mech Anal 99(2):91-114, 1987) proved that for any irrotational wave the angle must be less than 31.15°. Is the situation similar for periodic or solitary waves that are not irrotational? The extreme Gerstner wave has infinite depth, adverse vorticity and vertical cusps ( θ = 90°). Moreover, numerical calculations show that even waves of finite depth can overturn if the vorticity is adverse. In this paper, on the other hand, we prove an upper bound of 45° on {θ} for a large class of waves with favorable vorticity and finite depth. In particular, the vorticity can be any constant with the favorable sign. We also prove a series of general inequalities on the pressure within the fluid, including the fact that any overturning wave must have a pressure sink.

Leading across Boundaries and Silos in a Single Bound

ERIC Educational Resources Information Center

Lloyd, Christine

2016-01-01

Higher education is built on a long history of tradition, which, in many ways, has been impervious to outside pressures and influences. Despite having served as change agents for society, colleges and universities have resisted change for decades. Amid unprecedented pressure and scrutiny from outside stakeholders and dwindling state and federal…

Haematoporphyrin and OO'-diacetylhaematoporphyrin binding by serum and cellular proteins. Implications for the clearance of these photochemotherapeutic agents by cells.

PubMed Central

Smith, A; Neuschatz, T

1983-01-01

Haematoporphyrin derivative (HpD), a mixture of porphyrins, is currently used as a photochemotherapeutic agent in the treatment of neoplasias. The interaction of purified components of HpD with serum and cellular proteins was investigated using absorption and fluorescence spectroscopy. The interactions of haematoporphyrin and OO'-diacetylhaematoporphyrin with human albumin and with haemopexin, the two major serum porphyrin-binding proteins, show stoichiometries of 1 mol of porphyrin bound per mol of protein. The apparent dissociation constants, Kd, are in the range of 1-2 microM for albumin and 3-4 microM for haemopexin. These two major components of HpD would, after intravenous injection, bind to albumin and circulate in serum as albumin complexes. Free porphyrin rather than porphyrin bound to albumin interacts with Morris hepatoma tissue culture cells. A rapid high-affinity saturable transport system operates at free porphyrin concentrations of less than 2 microM. In addition, fluorescence spectra show that components in rat liver cytosol can bind haematoporphyrin and OO'-diacetylhaematoporphyrin and distinguish these binders from those present in rat serum. PMID:6225429

Synthesis and evaluation of novel polysaccharide-Gd-DTPA compounds as contrast agent for MRI

NASA Astrophysics Data System (ADS)

Sun, Guoying; Feng, Jianghua; Jing, Fengying; Pei, Fengkui; Liu, Maili

2003-09-01

Macromolecular conjugates of two kinds of natural polysaccharides, that from Panax quinquefolium linn (PQPS) and Ganoderma applanatum pat (GAPS), with gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA) have been synthesized and characterized by means of FTIR, elementary analysis and ICP-AES. Their stability was investigated by competition study with Ca 2+, EDTA (ethylenediaminetetraacetic acid) and DTPA. Polysaccharide-bound complexes exhibit T1 relaxivities of 1.5-1.7 times that of Gd-DTPA in D 2O at 25°C and 9.4 T. MR imaging of Sprague-Dawley (SD) rats showed remarkable enhancement in rat liver and kidney after i.v. injection of these two complexes: liver parenchyma 60.9±5.6%, 57.8±7.4% at 65-85 min; kidney 144.9±14.5%, 199.9±25.4% at 10-30 min for PQPS-Gd-DTPA, GAPS-Gd-DTPA at gadolinium dose of 0.083 and 0.082 mmol/kg, respectively. Our preliminary in vivo and in vitro study indicates that the two kinds of polysaccharide-bound complexes are potential tissue-specific contrast agents for MRI.

Distributed neural network control for adaptive synchronization of uncertain dynamical multiagent systems.

PubMed

Peng, Zhouhua; Wang, Dan; Zhang, Hongwei; Sun, Gang

2014-08-01

This paper addresses the leader-follower synchronization problem of uncertain dynamical multiagent systems with nonlinear dynamics. Distributed adaptive synchronization controllers are proposed based on the state information of neighboring agents. The control design is developed for both undirected and directed communication topologies without requiring the accurate model of each agent. This result is further extended to the output feedback case where a neighborhood observer is proposed based on relative output information of neighboring agents. Then, distributed observer-based synchronization controllers are derived and a parameter-dependent Riccati inequality is employed to prove the stability. This design has a favorable decouple property between the observer and the controller designs for nonlinear multiagent systems. For both cases, the developed controllers guarantee that the state of each agent synchronizes to that of the leader with bounded residual errors. Two illustrative examples validate the efficacy of the proposed methods.

Ant-inspired density estimation via random walks

PubMed Central

Musco, Cameron; Su, Hsin-Hao

2017-01-01

Many ant species use distributed population density estimation in applications ranging from quorum sensing, to task allocation, to appraisal of enemy colony strength. It has been shown that ants estimate local population density by tracking encounter rates: The higher the density, the more often the ants bump into each other. We study distributed density estimation from a theoretical perspective. We prove that a group of anonymous agents randomly walking on a grid are able to estimate their density within a small multiplicative error in few steps by measuring their rates of encounter with other agents. Despite dependencies inherent in the fact that nearby agents may collide repeatedly (and, worse, cannot recognize when this happens), our bound nearly matches what would be required to estimate density by independently sampling grid locations. From a biological perspective, our work helps shed light on how ants and other social insects can obtain relatively accurate density estimates via encounter rates. From a technical perspective, our analysis provides tools for understanding complex dependencies in the collision probabilities of multiple random walks. We bound the strength of these dependencies using local mixing properties of the underlying graph. Our results extend beyond the grid to more general graphs, and we discuss applications to size estimation for social networks, density estimation for robot swarms, and random walk-based sampling for sensor networks. PMID:28928146

Production, Labeling and In Vivo Studies with the Theranostic Positron-Emitting Radiometals 44Sc, 55/58m/58gCo, 61/64Cu, 86Y and 69Ge =

NASA Astrophysics Data System (ADS)

Valdovinos, Hector Francisco

In this dissertation, novel radiochemical separation methods for these radiometals that satisfy such requirements are presented, including a detailed characterization of the separated radionuclide in terms of radionuclidic purity, specific activity and spatial resolution in a small animal PET scanner. This dissertation also presents novel targetry and radiochemical separation methods for the production of less conventional radiometals that constitute "theranostic" (therapeutic and diagnostic) pairs, namely the Auger electron emitters 58mCo and 71Ge and their positron emitting complements 55Co and 69Ge. The theranostic potential of each radiometal is demonstrated first by collecting biodistribution data from PET imaging of tumor-bearing mice intravenously injected with radiolabeled agents, followed by internal dosimetry calculations focusing on the therapeutic and radiotoxic implications caused by the agent. Special attention is given to the radionuclides with intrinsic theranostic properties in themselves: 64Cu and the parent-daughter pair 58m/58gCo. The radiolabeled agents that are employed include the radiometal by itself, that is, weakly bound to a simple ligand in solution (all radiometals), as well as strongly bound to a chelator-conjugated tumor-targeting antibody called TRC105 (55Co, 58mCo, 58gCo, 64Cu and 86Y) or incorporated into the structure of a super paramagnetic iron oxide nanoparticle (69Ge).

A Multi Agent Based Approach for Prehospital Emergency Management.

PubMed

Safdari, Reza; Shoshtarian Malak, Jaleh; Mohammadzadeh, Niloofar; Danesh Shahraki, Azimeh

2017-07-01

To demonstrate an architecture to automate the prehospital emergency process to categorize the specialized care according to the situation at the right time for reducing the patient mortality and morbidity. Prehospital emergency process were analyzed using existing prehospital management systems, frameworks and the extracted process were modeled using sequence diagram in Rational Rose software. System main agents were identified and modeled via component diagram, considering the main system actors and by logically dividing business functionalities, finally the conceptual architecture for prehospital emergency management was proposed. The proposed architecture was simulated using Anylogic simulation software. Anylogic Agent Model, State Chart and Process Model were used to model the system. Multi agent systems (MAS) had a great success in distributed, complex and dynamic problem solving environments, and utilizing autonomous agents provides intelligent decision making capabilities.  The proposed architecture presents prehospital management operations. The main identified agents are: EMS Center, Ambulance, Traffic Station, Healthcare Provider, Patient, Consultation Center, National Medical Record System and quality of service monitoring agent. In a critical condition like prehospital emergency we are coping with sophisticated processes like ambulance navigation health care provider and service assignment, consultation, recalling patients past medical history through a centralized EHR system and monitoring healthcare quality in a real-time manner. The main advantage of our work has been the multi agent system utilization. Our Future work will include proposed architecture implementation and evaluation of its impact on patient quality care improvement.

A Multi Agent Based Approach for Prehospital Emergency Management

PubMed Central

Safdari, Reza; Shoshtarian Malak, Jaleh; Mohammadzadeh, Niloofar; Danesh Shahraki, Azimeh

2017-01-01

Objective: To demonstrate an architecture to automate the prehospital emergency process to categorize the specialized care according to the situation at the right time for reducing the patient mortality and morbidity. Methods: Prehospital emergency process were analyzed using existing prehospital management systems, frameworks and the extracted process were modeled using sequence diagram in Rational Rose software. System main agents were identified and modeled via component diagram, considering the main system actors and by logically dividing business functionalities, finally the conceptual architecture for prehospital emergency management was proposed. The proposed architecture was simulated using Anylogic simulation software. Anylogic Agent Model, State Chart and Process Model were used to model the system. Results: Multi agent systems (MAS) had a great success in distributed, complex and dynamic problem solving environments, and utilizing autonomous agents provides intelligent decision making capabilities.  The proposed architecture presents prehospital management operations. The main identified agents are: EMS Center, Ambulance, Traffic Station, Healthcare Provider, Patient, Consultation Center, National Medical Record System and quality of service monitoring agent. Conclusion: In a critical condition like prehospital emergency we are coping with sophisticated processes like ambulance navigation health care provider and service assignment, consultation, recalling patients past medical history through a centralized EHR system and monitoring healthcare quality in a real-time manner. The main advantage of our work has been the multi agent system utilization. Our Future work will include proposed architecture implementation and evaluation of its impact on patient quality care improvement. PMID:28795061

Are metallothioneins equally good biomarkers of metal and oxidative stress?

PubMed

Figueira, Etelvina; Branco, Diana; Antunes, Sara C; Gonçalves, Fernando; Freitas, Rosa

2012-10-01

Several researchers investigated the induction of metallothioneins (MTs) in the presence of metals, namely Cadmium (Cd). Fewer studies observed the induction of MTs due to oxidizing agents, and literature comparing the sensitivity of MTs to different stressors is even more scarce or even nonexistent. The role of MTs in metal and oxidative stress and thus their use as a stress biomarker, remains to be clearly elucidated. To better understand the role of MTs as a biomarker in Cerastoderma edule, a bivalve widely used as bioindicator, a laboratory assay was conducted aiming to assess the sensitivity of MTs to metal and oxidative stressors. For this purpose, Cd was used to induce metal stress, whereas hydrogen peroxide (H2O2), being an oxidizing compound, was used to impose oxidative stress. Results showed that induction of MTs occurred at very different levels in metal and oxidative stress. In the presence of the oxidizing agent (H2O2), MTs only increased significantly when the degree of oxidative stress was very high, and mortality rates were higher than 50 percent. On the contrary, C. edule survived to all Cd concentrations used and significant MTs increases, compared to the control, were observed in all Cd exposures. The present work also revealed that the number of ions and the metal bound to MTs varied with the exposure conditions. In the absence of disturbance, MTs bound most (60-70 percent) of the essential metals (Zn and Cu) in solution. In stressful situations, such as the exposure to Cd and H2O2, MTs did not bind to Cu and bound less to Zn. When organisms were exposed to Cd, the total number of ions bound per MT molecule did not change, compared to control. However the sort of ions bound per MT molecule differed; part of the Zn and all Cu ions where displaced by Cd ions. For organisms exposed to H2O2, each MT molecule bound less than half of the ions compared to control and Cd conditions, which indicates a partial oxidation of thiol groups in the cysteine residues through ROS scavenging. The present results suggest that MTs are excellent markers of metal stress, but not of oxidative stress. Copyright © 2012 Elsevier Inc. All rights reserved.

A Functional Model of Sensemaking in a Neurocognitive Architecture (Open Access, Publisher’s Version)

DTIC Science & Technology

2013-07-08

bias. Moreover, it is to be expected that a rational agent learns and adapts its strategies and knowledge, its metacognitive control (e.g., more...Pirolli and S. K. Card, “The sensemaking process and leverage points for analyst technology ,” inProceedings of the International Conference on...user: the sense- making of qualitative-quantitative methodology,” in Sense- Making Methodology Reader: Selected Writings of Brenda Dervin, B. Dervin, L

Forecasting The Future Of The Islamic State: An Agent Based Rational Choice Model And Social Network Analysis Approach

DTIC Science & Technology

2017-12-01

Mesquita, B., Smith, A., Siverson, M. R., & Morrow, D. J . (2005). The logic of political survival. Cambridge, MA: MIT Press. Bunzel, C . (2015). From...communications-legacy-is-here-to-stay/ Clarke, P. C ., Jackson, K., Johnston, B. P., Robinson, E., & Shatz, J . H. (2017). Financial futures of the...Cunningham, C . F., & Braithwaite, J . (2013). Bridges, brokers and boundary spanners in collaborative networks: A systematic review. BMC Health Services

An Agent for the Prospect Presentation Problem

DTIC Science & Technology

2014-05-01

Economics, 12:133–158. [18] Daniel Kahneman . Thinking , fast and slow . Allen Lane, London, 2011. [19] Daniel Kahneman and Amos Tversky. Prospect theory...u(X) = log(X) (2) 2.2 Prospect Theory The Prospect Theory was presented by Kahneman and Tversky in [19] and later refined to the Cumulative Prospect...fully rationally, but rather use their own de- cision weights when deciding whether to reject or accept a gamble. In his book, Kahneman [18] (p.314

Balancing Antioxidant, Hypolipidemic and Anti-inflammatory Activity in a Single Agent: The Example of 2-Hydroxy-2-Substituted Morpholine, 1,4-Benzoxazine and 1,4-Benzothiazine Derivatives as a Rational Therapeutic Approach against Atherosclerosis.

PubMed

Matralis, Alexios N; Bavavea, Eugenia-Ismini; Incerpi, Sandra; Pedersen, Jens Z; Kourounakis, Angeliki P

2017-01-01

In line with our previous studies, novel morpholine and benzoxa(or thia)zine lead compounds have been developed through a rational design that modulate a multiplicity of targets against atherosclerosis. We have evaluated the most promising compounds for their efficiency to a) intercept and scavenge free radicals, b) inhibit the metal ion (Cu2+)- induced LDL oxidation c) act intracellularly as antioxidants in THP-1 monocytes from a leukemic patient and d) inhibit the pro-inflammatory enzymes cyclooxygenase-1 (COX-1) and -2 (COX-2) in vitro. Furthermore, two representative compounds were tested for their potential to decrease lipidemic parameters (TC, LDL and TG) in hyperlipidemic mice. Most derivatives indicated a remarkable antioxidant activity, while at the same time exhibited a significant in vitro anti-inflammatory activity, inhibiting COX-1 or/and COX-2 activity at 20 μΜ. In addition, after their long-term administration, compounds 6 and 8 afforded considerable activity in a chronic experimental animal model of hyperlipidemia (after high fat diet administration). The multifunctional pharmacological profile exhibited by the compounds of this study renders them interesting lead compounds for the development of novel agents against atherosclerosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.