bluuebunny/crossref_metadata_2025 huggingface dataset:
Data Mining in Construction Bidding Policy
Authors: Williams Trefor
Published: June 2010

Many construction projects are selected using competitive bidding, where the lowest bidder wins the project. There is often a tendency for projects to cost more than the original bid amount. The data mining techniques of classification and association were used to study patterns in bidding data and to determine if useful patterns do exist that can help predict a projects tendency to have cost overruns. Using highway‐bidding data from Texas highway projects, several different ratios were calculated to describe relationships between the submitted bids such as the spread of the submitted bid and the difference between the low bid and the second lowest bid. Elevated levels of these ratios have been found to be associated with projects that have significant deviations between the original low bid amount and the completed project cost. The tertius and predictivea prioriassociation algorithms, and the Ridor classification algorithm were applied to the data set to determine if useful rules about a projects tendency to have cost overruns could be determined.
Decision Making Under Pressure and Constraints: Bounded Rationality
Authors: Kirlik Alex , Bertel Sven
Published: June 2010

The origins of bounded rationality in the pioneering research of Herbert A. Simon are presented, and the influence of these original ideas are traced forward to examine how they have influenced a wide variety of contemporary lines of psychological research on both, the capabilities and mechanisms of human judgment and decision making.
Discrete‐Time Martingales
Authors: Lin Kyle Y.
Published: June 2010

Discrete‐time martingales are stochastic processes motivated by a sequence of fair bets. If the expected winning of each bet is equal to 0 and their outcomes are independent, then the gambler's expected fortune after the next bet is equal to his current fortune. In this example, the sequence of random variables {
Z
1
,
Z
2
, …}, with
Z

n

denoting the gambler's fortune after
n
bets,
n
 = 1, 2, …, is said to be a discrete‐time martingale. This article gives the definition of discrete‐time martingales and provides several examples.
Distributed Simulation inORMS
Authors: Taylor Simon J.E. , Mustafee Navonil
Published: June 2010

Commercial off‐the‐shelf (COTS) simulation packages (CSPs) are tools typically used in Operational Research and Management Science for discrete‐event simulation. Distributed simulations using these can be widely beneficial. These require CSP interoperability, that is, a set of techniques that facilitate the execution of a distributed simulation over several computers or for several simulations running on different computers to run together. This article introduces reasons for using distributed simulation and CSP interoperability. A set of guiding techniques used to simplify their realization is then presented. A case study of a health‐care application is used to demonstrate how these are used in practice.
Emergency Medical Service Systems that Improve Patient Survivability
Authors: McLay Laura A.
Published: June 2010

The goal of emergency medical service (EMS) systems is to save lives. Although EMS systems traditionally deploy their units at fixed locations (i.e., “stations”), this is not necessarily the optimal way to respond when resources are limited. This article summarizes the key issues in defining performance measures, utilizing scarce emergency medical resources, and assessing EMS performance when applying operations research methodologies to EMS systems and explicitly focusing on patient outcomes. This article overviews standards currently used by many EMS systems and proposes several performance measures to use in operations research models for EMS systems. Several areas within EMS system design that could benefit from the application of operations research methodologies are described.
Estimating Failure Rates and Hazard Functions
Authors: Giorgio Massimiliano , Pulcini Gianpaolo
Published: June 2010

This article illustrates a number of classical nonparametric and parametric procedures for estimating the failure rate (often called the hazard function) and the cumulative failure rate of non repairable units. Both point and interval estimation procedures are discussed and some graphical methods are briefly presented. A specific attention is devoted to two distribution functions frequently used in the reliability analysis: the standard exponential and the two‐parameter Weibull distributions. Finally, some numerical examples are given to illustrate the estimation procedures.
Hazard Rate Function
Authors: Upadhyay Satyanshu Kumar
Published: June 2010

Hazard rate function is an important concept for researchers and practitioners working in areas such as engineering statistics, and biomedical sciences. Hazard rate in fact provides an alternative characterization for the distribution of a random variable, especially when dealing with the lifetime data and it is quite useful in defining and formulating a model. The present article begins with a discussion on how the notion of hazard rate function enters into lifetime data analysis, and provides the general concept and definition of the hazard function for both continuous and discrete variates. The article finally focuses on a few typical shapes of the hazard rate function and comments briefly on some important models that can be useful for the considered shapes. Additional list of references is provided at the end for supplemental reading.
H
olt–
W
inters Exponential Smoothing
Authors: Pan Rong
Published: June 2010

The Holt–Winters exponential smoothing method was first introduced more than half a century ago for the seasonal time series forecast and it is still one of the most popular forecasting systems widely used in production planning, inventory control, and many other application areas. Numerous empirical studies have confirmed the accuracy and robustness of this simple method, compared to many other sophisticated forecasting techniques. Recently, the underlying optimal time series models of this heuristic method have been found and they provide the theoretical foundation for obtaining the statistical properties of this method. This article aims to provide a succinct summary of the basic Holt–Winters method and help readers understand and appreciate this simple, yet powerful, forecasting technique.
Introduction to Stochastic Approximation
Authors: Yin George
Published: June 2010

This article is concerned with the stochastic approximation method. It provides an overview of the subject together with a brief account on the literature and recent developments. The connection to dynamic systems is illustrated through the discrete iterations and ordinary differential equations.
k‐out‐of‐nSystems
Authors: Zuo Ming J. , Tian Zhigang
Published: June 2010

In this article, we focus on thek‐out‐of‐nsystem structure. This structure is a widely used type of redundancy in both industrial and military systems. In the binaryk‐out‐of‐nsystem models, it is assumed that the system and the components can take only two possible states, completely working or totally failed. In the multistatek‐out‐of‐nsystem and the weighted multistatek‐out‐of‐nsystem models, it is assumed that the system and the components can take multiple discrete states. For all thesek‐out‐of‐nsystem models, algorithms for evaluation of the system state distribution are investigated given component state distributions are investigated.
Large Margin Rule‐Based Classifiers
Authors: Bonates Tibérius O.
Published: June 2010

We introduce an optimization approach for the construction of large margin rule‐based classifiers. We base our description on the Logical Analysis of Data (LAD) methodology, but the same approach can be applied to different rule‐based classification algorithms. The novelty in our algorithm relies on the fact that it unifies the distinct tasks of pattern (rule) generation and creation of a so‐calleddiscriminant functionfor classification. Moreover, the algorithm has a single parameter, thus, significantly reducing the necessity for parameter calibration when learning a new data set. We investigate how accurate the LAD classification models built with our algorithm are and how they compare to other machine learning models.
Load‐Sharing Systems
Authors: Dewan Isha , Naik‐Nimbalkar Uttara V.
Published: June 2010

Load‐sharing systems arise in several real‐life situations. Some of them have been described below. Several models proposed in the literature for load‐sharing systems are studied. The emphasis is on parametric estimation and testing and nonparametric estimation of system life distributions under equal and monotone load‐sharing rules. Data sets that describe load‐sharing systems have been described. A few probabilistic results are stated for completeness.
Operation Research in Golf
Authors: Hurley Willam J.
Published: June 2010

In this article, operations research techniques as applied to the sport of golf are described. Promising directions for future research are given.
An Overview of Operations Research in Tennis
Authors: Pollard Geoff , Meyer Denny
Published: June 2010

For nearly 100 years, the equipment and the rules of tennis hardly changed. But since the opening of the game to professionals as well as amateurs in 1968, and the expansion of the game worldwide and in the media, scientific and technological developments have created both problems and opportunities for tennis. This article looks at the use and opportunities for operations research and management science methods to analyze the unique tennis scoring system and the optimal strategies and techniques players might employ. It also considers the use of these methods for the optimization of tennis equipment, including court surface and line calling, and coaching while minimizing medical risk. Efficient tournament management and the accuracy of player ranking are also addressed. This article describes how modern developments allow a scientific approach to measuring and categorizing while suggesting that it may be necessary to limit developments in order to maintain the character of the game.
Paradoxes and Violations of Normative Decision Theory
Authors: Simon Jay , Wang Yitong , Keller L. Robin
Published: June 2010

In this article, first classic examples of descriptive violations of normative decision theory from Allais and Ellsberg are discussed, and then the behavioral phenomena of loss aversion, endowment effect, status quo bias, and framing effects are discussed.
Parallel Discrete‐Event Simulation
Authors: Liu Jason
Published: June 2010

Parallel discrete‐event simulation (PDES), sometimes simply referred to asparallel simulation, is concerned with the execution of discrete‐event simulation on parallel computers. PDES has been recognized as a challenging field of research bridging modeling and simulation, and high‐performance computing. By exploiting the potential parallelism in a simulation model, PDES can overcome the limitations imposed by sequential simulation, both in the execution time and the memory space. It has been demonstrated to be a viable technique for solving large‐scale complex models. In this article, we provide a brief overview of the current state of PDES, identify its fundamental challenges, and discuss existing principal solutions resulting from three decades of intensive research in this field. Further, we report specific research advances in high‐performance modeling and simulation of large‐scale computer networks as an exemplar of typical PDES applications.
Point and Interval Availability
Authors: Aven Terje
Published: June 2010

Consider a system that is repaired or replaced at failures. The problem is to analyze the availability of the system, at a fixed point in time or for an interval [u,v]. This article presents models and methods for analyzing the availability, both for one‐unit systems and more complex systems comprising several components (monotone systems). Exact formulae as well as approximation approaches based on asymptotic results are covered.
Pricing and Replenishment Decisions
Authors: Bernstein Fernando
Published: June 2010

This article reviews recent work addressing the joint determination of prices and inventory replenishment strategies. The article discusses papers that analyze pricing and replenishment decisions in settings with a single firm and in settings that consider the interaction of multiple firms.
Reduction of aPOMDPto anMDP
Authors: Sandikçi Burhaneddin
Published: June 2010

A partially observable Markov decision process (POMDP) is an appropriate mathematical modeling tool for dynamic stochastic systems where portions or all of the system states are not completely observable to the decision maker. In this respect, POMDPs generalize completely observable Markov decision processes (MDPs) by allowing infinitely many states to address partial observability. However, the resulting models suffer tremendously from computational intractability even for relatively small problems. Therefore, POMDPs are frequently approximated by solving variants of completely observable MDPs defined on a grid of finite states. This article summarizes the relationships between completely and partially observable MDPs and derives inequalities for the POMDP value function using the optimal value function of the grid‐based MDPs.
Remanufacturing
Authors: Souza Gilvan C.
Published: June 2010

In this article, we provide a general introduction to remanufacturing and closed‐loop supply chains. Closed‐loop supply chains are those where there are flow of used products (“returns”) from consumers back to manufacturers and suppliers. A key disposition alternative for returns is remanufacturing: the process of restoring used products to a common aesthetic and functional standard. We first introduce the terminology: types of returns (end‐of‐life, end‐of‐use, consumer returns), and disposition decisions for returns (incineration, recycling, sell as‐is, parts harvesting, remanufacturing). We distinguish a key unique characteristic of remanufacturing: in contrast to manufacturing, the inputs—product returns—in remanufacturing are variable with respect to quality, quantity, and timing. We then show how operations research can be used to help the remanufacturing firm price its products (relative to comparable new products), and plan its production, considering the variable input stream.
Scoring Rules
Authors: Winkler Robert L. , Jose Victor Richmond R.
Published: June 2010

Probabilities are used to quantify uncertainty in operations research and management science modeling. Scoring rules provide a numerical measure (a score or reward) based on probabilities for an event or variable and on what actually occurs. As such, they are valuable in evaluating how “good” probabilities are in light of what happens, and they also provide incentives for careful elicitation of probabilities. We discuss basic properties of scoring rules, present families of scoring rules that are useful under various conditions, and discuss some related issues.
Sequential Decision Problems Under Uncertainty
Authors: White Chelsea C.
Published: June 2010

In this article, sequential decision problems under uncertainty are considered. The general features of these problems are given and there is a discussion of practical solutions and how these solutions can be obtained. Several variations of the standard problems statement are shown.
Simplifying and Solving Decision Problems by Stochastic Dominance Relations
Authors: Eeckhoudt Louis , Schlesinger Harris , Tsetlin Ilia
Published: June 2010

Stochastic dominance is a formal statistical property that partially orders probability distributions. If two alternatives can be ordered by the stochastic dominance criterion, then all individuals whose utility functions satisfy a few easy‐to‐verify criteria will unanimously prefer the dominant alternative. We review several extant characterizations of stochastic dominance, including a recent result that shows how stochastic dominance can be linked to a preference for combining “good” and “bad” outcomes. In particular, if a decision context is about allocating pairs of alternatives in two different states, then lotteries between two “good‐bad” pairs dominate lotteries that yield both “bad” alternatives in one state versus both “good” alternatives in the other state. We explain this dominance relationship and show how it can be used in solving several decision problems involving choice under risk. We also show how individual preference for always pairing such good with bad alternatives implies utility that is a weighted average of exponential functions, which can each be characterized as exhibiting constant absolute risk aversion (CARA). Thus, if preference for one alternative over the others holds under CARA with a wide range of risk aversion coefficients, the decision can be determined with only a limited amount of information about the decision maker's particular utility function.
Sociedad Peruana De Investigación Operativa
Y
De Sistemas (
SOPIOS
)
Authors: Delgadillo Rosa , Mauricio David
Published: June 2010

In this article the History of Peruvian Society of Operations Research and Systems (Sociedad Peruana de Investigación Operativa y de Sistemas (SOPIOS)) is presented. It details the antecedents and the creation of SOPIOS, as well as its objectives, the activities it realizes, and the achievements reached to date and the perspectives of society.
Stakeholder Participation
Authors: Heath Robert L.
Published: June 2010

As a substantial and growing body of research, theory, and best practices, stakeholder participation addresses the structures, functions, and meaning constructions that shape ethical and effective stakeholder relations as a point of orientation for effective management and operations. The logic centers on the need organizations have for resource others hold. It features the willingness and ability of those others to yield (and seek reciprocation) stakes in mutually beneficial exchange as the rationale for marketplace and public policy negotiations. This analysis leads to enlightened and reflective management styles and collaborative decision making.
Stochastic Optimal Control Formulations of Decision Problems
Authors: Srivastava Kunal , Stipanović Dušan M.
Published: June 2010

In this article, we give a brief overview of different stochastic optimal control problems that arise in decision problems. An informal derivation of the Hamilton–Jacobi–Bellman equation, which characterizes the optimal policy, is derived for the case of full state infinite horizon optimal control problem. We then discuss the optimal control problem where the horizon is governed by a random stopping time. An example illustrating the application of the theory to a portfolio selection problem is provided. After a brief discussion on ergodic and risk sensitive control formulations, we move to the case when the state is partially observed. We then state the key separation result in this case and provide some intuitive explanation.
Supplier Selection
Authors: Beil Damian R.
Published: June 2010

Supplier selection is the process by which firms identify, evaluate, and contract with suppliers. The supplier selection process deploys a tremendous amount of a firm's financial resources. In return, firms expect significant benefits from contracting with suppliers offering high value. This article describes the typical steps of supplier selection processes: identifying suppliers, soliciting information from suppliers, setting contract terms, negotiating with suppliers, and evaluating suppliers. It highlights why each step is important, how the steps are interrelated, and how the resulting complexity provides fertile ground for ORMS research.
Take‐Back Legislation and Its Impact on Closed‐Loop Supply Chains
Authors: Atasu Atalay , Boyaci Tamer
Published: June 2010

In this article, we introduce and exemplify existing legislation that regulates the end‐of‐life processing of used products and discuss potential implications of such legislation on closed‐loop supply chains (CLSCs). Using a generic CLSC model, we provide our perspective on how such legislation in general influences different stakeholders in CLSCs.
Using Queueing Theory to Alleviate Emergency Department Overcrowding
Authors: Green Linda V.
Published: June 2010

Emergency Department (ED) overcrowding is a growing problem in the United States and many other countries. Though sometimes dismissed as a minor issue caused by an increase in those who use the ED for routine medical care, this masks the potentially fatal consequences for seriously ill patients who do not receive timely care. This article will illustrate how problems in emergency responsiveness are often due to capacity management policies used by hospital managers and government officials which are based on an erroneous understanding of service system dynamics. Examples will show how the use of queueing models can help identify root causes of ED overcrowding and identify better policies for resource allocation and management that will result in significant improvements, often with little or no additional capacity.
Semi‐Markov Processes and Hidden Models
Authors: Limnios Nikolaos
Published: June 2010

The purpose of this article is to present the semi‐Markov processes focusing on applications, especially in reliability and dependability. The semi‐Markov processes under consideration are both of continuous and discrete time with countable or finite state space. The basic definitions of Markov renewal and semi‐Markov processes are presented, as well as the Markov renewal theorem and the some theory of statistical estimation. In the sequel, we describe a general reliability model and give the corresponding estimations. Finally, we briefly present the semi‐Markov chain and hidden semi‐Markov models. Some bibliographical directions for further relevant topics, which are not included in this article, are given.
Availability Analysis: Concepts and Methods
Authors: Zio Enrico
Published: June 2010

Availability is a concept used to characterize the performance of a machine, component, or system with respect to its ability to fulfill the function for which it is operated. In this article, a general introduction to quantitative modeling for the availability analysis of components and systems is provided. Both, cases of continuously monitored and periodically tested components are considered. Markov modeling and Monte Carlo simulation are presented as methods for the evaluation of the availability of complex systems.
TG101209, a novel JAK2 inhibitor, has significant in vitro activity in multiple myeloma and displays preferential cytotoxicity for CD45+ myeloma cells
Authors: Ramakrishnan Vijay , Kimlinger Teresa , Haug Jessica , Timm Michael , Wellik Linda , Halling Timothy , Pardanani Animesh , Tefferi Ayalew , Vincent Rajkumar Sundararasan , Kumar Shaji
Published: June 2010

Interaction of myeloma cells with the bone marrow microenvironment is mediated in large part through different cytokines, especially VEGF and IL6. These cytokines, especially IL6, leads to upregulation of the JAK/STAT pathway in myeloma cell, contributing to increased proliferation, decreased apoptosis, and acquired drug resistance. Here, we examined the preclinical activity of a novel JAK2 inhibitor TG101209. TG101209 induced dose‐ and time‐dependent cytotoxicity in a variety of multiple myeloma (MM) cell lines. The induction of cytotoxicity was associated with inhibition of cell cycle progression and induction of apoptosis in myeloma cell lines and patient‐derived plasma cells. Evaluation of U266 cell lines and patient cells, which have a mix of CD45 positive and negative cells, demonstrated more profound cytotoxicity and antiproliferative activity of the drug on the CD45+ population relative to the CD45− cells. Exploring the mechanism of action of TG101209 indicated downregulation of pJak2, pStat3, and Bcl‐xl levels with upregulation of pErk and pAkt levels indicating cross talk between signaling pathways. TG101209, when used in combination with the PI3K inhibitor LY294002, demonstrated synergistic cytotoxicity against myeloma cells. Our results provide the rationale for clinical evaluation of TG101209 alone or in combination with PI3K/Akt inhibitors in MM. Am. J. Hematol., 2010. © 2010 Wiley‐Liss, Inc.
A novel initiating system for ring‐opening polymerization of ε‐caprolactone: Synthesis of triarm star‐shaped poly(ε‐caprolactone)
Authors: Zhu Weipu , Tong Xiaowei , Xie Weihui , Shen Zhiquan
Published: June 2010

The rare earth compound, scandium trifluoromethanesulfonate [Sc(OTf)3], has been used as a water‐tolerant catalyst for the synthesis of star‐shaped poly(ε‐caprolactone)s (SPCLs) with trimethylol propane as trifunctional initiator in solvent at 40°C. Triarm SPCLs have been successfully prepared. The molar mass of SPCLs were determined by end‐group 1H NMR analyses, which could be well controlled by the molar ratio of the monomer to the initiator, and were independent of the amount of Sc(OTf)3 used. Differential scanning calorimetry analyses suggested that the maximal melting point, the cold crystallization temperature, and the degree of crystallinities of SPCLs increased with the increasing of the molar mass and were lower than the linear poly(ε‐caprolactone) (LPCL) with similar molar mass. Furthermore, polarized optical microscopy indicated that LPCL showed fast crystallization rate and good spherulitic morphology with apparent Maltese cross pattern, whereas SPCLs exhibit much lower crystallization rate and poor spherulitic morphology. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Bubble growth in the microcellular foaming of CO2/polypropylene solutions
Authors: Zhang Ping , Wang Xiao‐Jun , Yang Yong , Zhou Nan‐Qiao
Published: June 2010

This article is concerned with bubble growth dynamics in the CO2/polypropylene microcellular foaming process. The effect of the melt strength on the bubble growth was thoroughly investigated in theory for the first time. The theoretical results indicate that enhanced melt strength effectively restrains the bubble growth and stabilizes the bubble oscillation. Higher melt strength leads to lower bubble growth rate, shorter growth time, and smaller ultimate bubble size. Compared to the melt strength, the viscoelasticity and the gas pressure have less effect on the microcellular foaming process. The bubble growth varies a little as the viscoelasticity is varied. The bubble oscillation and growth rate are enhanced with increasing gas pressure, which leads to the augmentation of the bubble size. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
The comparative study of photocatalytic self‐cleaning properties of synthesized nanoscale titania and zirconia onto polyacrylonitrile fibers
Authors: Moafi Hadi Fallah , Shojaie Abdollah Fallah , Zanjanchi Mohammad Ali
Published: June 2010

The photocatalytic activity of TiO2 and ZrO2‐coated polyacrylonitrile (PAN) fibers was compared through the self‐cleaning of methylene blue and eosin yellowish. TiO2 and ZrO2 nanocrystals were successfully synthesized and deposited onto PAN fibers with photocatalytic self‐cleaning activity using the sol‐gel process at low temperature. The pristine and treated samples have been characterized by several techniques, such as scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, diffuse reflectance spectroscopy, X‐ray diffraction, and thermogravimetric analysis. The TiO2 nanoparticles with 10–20 nm in size, and ZrO2 with 20–40 nm have been synthesized to form dispersed particles on the fiber surface, which shows photocatalytic properties when exposed to UV–Vis light. The photocatalytic activity, tested by measuring the degradation of adsorbed methylene blue and Eosin Y. Photocatalytic activity of TiO2‐coated fibers toward dyes degradation was higher than that of ZrO2‐coated fibers. This preparation technique can be also applied to new fabrics to create self‐cleaning and UV irradiation protection properties in them. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Controlled size chitosan nanoparticles as an efficient, biocompatible oligonucleotides delivery system
Authors: Manchanda Romila , Nimesh Surendra
Published: June 2010

Polymeric nanoparticles of chitosan crosslinked with glutaraldehyde have been prepared using reverse micellar system. An optically clear solution was obtained on redispersing these nanoparticles in aqueous buffer. The nanoparticles were characterized for their size and surface morphology employing dynamic laser scattering (DLS) and transmission electron microscopy (TEM). The TEM images showed spherical particles with smooth surface and narrow size distribution of about 90 nm, which was also supported by DLS data. Size and morphology of the particles remains the same on redispersing the lyophilized powder of these nanoparticles in aqueous buffer. Further, these nanoparticles were loaded with different synthetic oligonucleotides (ODNs). In vitro pH dependent release of the adsorbed oligonucleotides from these nanoparticles was also studied. At basic pH the release of oligonucleotides was found higher as compared with neutral and acidic medium. Cytotoxicity studies done on HEK 293 cells reveals that oligonucleotide loaded nanoparticles have high cell viability of nearly 76–88% whereas those of lipofectamine was about 35%. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Use of Side‐Chain Incompatibility for Tailoring Long‐Range p/n Heterojunctions: Photoconductive Nanofibers Formed by Self‐Assembly of an Amphiphilic Donor–Acceptor Dyad Consisting of Oligothiophene and Perylenediimide
Authors: Li Wei‐Shi , Saeki Akinori , Yamamoto Yohei , Fukushima Takanori , Seki Shu , Ishii Noriyuki , Kato Kenichi , Takata Masaki , Aida Takuzo
Published: June 2010

To tailor organic p/n heterojunctions with molecular‐level precision, a rational design strategy using side‐chain incompatibility of a covalently connected donor–acceptor (D–A) dyad has been successfully carried out. An oligothiophene–perylenediimide dyad, when modified with triethylene glycol side chains at one terminus and dodecyl side chains at the other (2 Amphi), self‐assembles into nanofibers with a long‐range D/A heterojunction. In contrast, when the dyad is modified with dodecyl side chains at both termini (2 Lipo), ill‐defined microfibers result. In steady‐state measurements using microgap electrodes, a cast film of the nanofiber of 2 Amphi displays far better photoconducting properties than that of the microfiber of 2 Lipo. Flash‐photolysis time‐resolved microwave conductivity measurements, in conjunction with transient absorption spectroscopy, clearly indicate that the nanofiber of 2 Amphi intrinsically allows for better carrier generation and transport properties than the microfibrous assembly of 2 Lipo.
Effects of the isoflavonoid biochanin A on the transport of mitoxantronein vitroandin vivo
Authors: An Guohua , Morris Marilyn E.
Published: June 2010

The aim of our study was to investigate the effect of biochanin A on the accumulation and transport of mitoxantrone in breast cancer resistance protein (BCRP)‐expressing normal cells and its impact on the pharmacokinetics (PK) and tissue distribution of mitoxantrone. In accumulation studies, the intracellular level of mitoxantrone was significantly increased in the presence of 2.5 or 25 µMof biochanin A in both murine and human BCRP‐expressing Madin‐Darby canine kidney (MDCK) cells, with no effect in corresponding MDCK/Mock cells. In bi‐directional transport studies, thePapp,B‐Avalue of mitoxantrone with biochanin A co‐treatment was much lower (6.66±0.84×10−7 cm/s) than that in the absence of biochanin A (21.4±4.14×10−7 cm/s), indicating inhibition of Bcrp1‐mediated efflux. To evaluate whether ourin vitroresults might translate into anin vivointeraction, mitoxantrone PK and tissue distribution, with and without co‐administration of biochanin A, was investigated. In contrast to ourin vitroresults, biochanin A (10 mg/kg, i.v.) had no impact on the concentration of mitoxantrone in plasma and most tissues collected (brain, heart, liver and lung). Surprisingly, the concentrations of mitoxantrone in spleen and kidney were even decreased when biochanin A was co‐administered. Interestingly, it was found that the intracellular fluorescence of mitoxantrone was decreased 31.9% when co‐incubated with 10 µMbiochanin A in P‐glycoprotein (P‐gp) expressing MCF‐7/ADR cells, indicating potential P‐gp stimulation. The species difference of the inhibitory effect of biochanin A on BCRP, the extensive metabolism of biochanin A, as well as the stimulation effect of biochanin A on P‐gp, may contribute to thisin vitro–in vivodisconnect. Copyright © 2010 John Wiley & Sons, Ltd.
Methylnitrosourea induces neural progenitor cell apoptosis and microcephaly in mouse embryos
Authors: Komada Munekazu , Fujiyama Fusako , Yamada Shigehito , Shiota Kohei , Nagao Tetsuji
Published: June 2010

BACKGROUND: Prenatal exposure to methylnitrosourea (MNU), an alkylating agent, induces microcephaly in mice. However, its pathogenetic mechanism has not been clarified, especially that in the development of the cerebral cortex. METHODS: ICR mice were treated with MNU at 10 mg/kg intraperitoneally on day 13.5 or 15.5 of gestation, and the embryos were observed histologically 24 hr after treatment with MNU or at term. To clarify the pathogenesis of microcephaly and histological changes, especially apoptosis, neurogenesis, and neural migration/positioning, we performed histological analysis employing a cell‐specific labeling experiment using thymidine‐like substances (BrdU, CldU, and IdU) and markers of neurons/neural stem cells. RESULTS: Histological abnormalities of the dorsal telencephalon, and the excessive cell death of proliferative neural progenitor/stem cells were noted in the MNU‐treated embryos. The highest frequencies of cell death occurred at 36 hr after MNU treatment, and little or no neurogenesis was observed in the ventricular zone of the dorsal telencephalon. Abnormality of the radial migration was caused by the reduction of radial fibers in the radial glias. Birth‐date analysis revealed the abnormal positioning of neurons and aberrant lamination of the cerebral cortex. CONCLUSIONS: Our data suggest that prenatal exposure to MNU induces the excessive cell death of neural precursor/stem cells, and the defective development of the cerebral cortex, resulting in microcephalic abnormalities. Birth Defects Res (Part B) 89:213–222, 2010. © 2010 Wiley‐Liss, Inc.
A comparison of the effects of prenatal exposure of CD‐1 mice to three imidazolium‐based ionic liquids
Authors: Bailey Melissa M. , Jernigan Peter L. , Henson Megan B. , Sturdivant John , Rasco Jane F. , Lovich Ashley N. , Lockhard Jarrett E. , Hough Whitney L. , Di Bona Kristin R. , Beaird Janis , Sherrill Jonathan , Swatloski Richard P. , Rogers Robin D. , Hood Ronald D.
Published: June 2010

BACKGROUND: Ionic liquids (ILs; salts with melting points below 100°C) exhibit wide liquid ranges, non‐flammability, and thermal stability among other properties. These unique salts are best known as “green” alternatives to traditional volatile organic solvents, which are utilized in both academia and industry. Our current study compares the developmental toxicity potential of three representative ionic liquids, with various chain lengths: 1‐ethyl‐3‐methylimidazolium chloride ([C2mim]Cl), 1‐butyl‐3‐methylimidazolium chloride ([C4mim]Cl), and 1‐decyl‐3methylimidazolium chloride ([C10mim]Cl). METHODS: From gestation days (GD) 6‐16, mated CD‐1 mice were orally dosed with one of the following: 1,000, 2,000, or 3,000 mg/kg/day [C2mim]Cl; 113, 169, or 225 mg/kg/day [C4mim]Cl; 50, 75, or 100 mg/kg/day [C10mim]Cl; or the vehicle only. Dams were sacrificed on GD 17, and their litters were examined for adverse effects. RESULTS: Fetal weight was significantly decreased in the two highest dosage groups exposed to [C4mim]Cl and [C10mim]Cl in comparison with their controls, but the [C2mim]Cl treated groups were not affected. An apparent teratogenic effect was associated with both [C4mim]Cl and [C10mim]Cl, as the offspring exhibited certain uncommon morphological defects. However, the incidences of malformations were low and no correlation between incidence and dosage could be made. No morphological defects were observed in any of the [C2mim]Cl‐treated groups, despite maternal morbidity at the highest dosage level. CONCLUSIONS: This study indicates that [C4mim]Cl and [C10mim]Cl may have adverse effects on development at high maternal exposures and strongly supports the supposition that the toxicity of imidazolium‐based ILs is influenced by alkyl chain length. Birth Defects Res (Part B) 89:233–238, 2010. © 2010 Wiley‐Liss, Inc.
Cooperation and cheating in microbial exoenzyme production – Theoretical analysis for biotechnological applications
Authors: Schuster Stefan , Kreft Jan‐Ulrich , Brenner Naama , Wessely Frank , Theißen Günter , Ruppin Eytan , Schroeter Anja
Published: June 2010

The engineering of microorganisms to produce a variety of extracellular enzymes (exoenzymes), for example for producing renewable fuels and in biodegradation of xenobiotics, has recently attracted increasing interest. Productivity is often reduced by “cheater” mutants, which are deficient in exoenzyme production and benefit from the product provided by the “cooperating” cells. We present a game‐theoretical model to analyze population structure and exoenzyme productivity in terms of biotechnologically relevant parameters. For any given population density, three distinct regimes are predicted: when the metabolic effort for exoenzyme production and secretion is low, all cells cooperate; at intermediate metabolic costs, cooperators and cheaters coexist; while at high costs, all cells use the cheating strategy. These regimes correspond to the harmony game, snowdrift game, and Prisoner's Dilemma, respectively. Thus, our results indicate that microbial strains engineered for exoenzyme production will not, under appropriate conditions, be outcompeted by cheater mutants. We also analyze the dependence of the population structure on cell density. At low costs, the fraction of cooperating cells increases with decreasing cell density and reaches unity at a critical threshold. Our model provides an estimate of the cell density maximizing exoenzyme production.
Downhill binding energy surface of the barnase–barstar complex
Authors: Wang Ling , Siu Shirley W. I. , Gu Wei , Helms Volkhard
Published: June 2010

We have employed biased molecular dynamics simulations in explicit solvent to characterize the one‐dimensional potential of mean force for the dissociation process of the barnase–barstar protein–protein complex. Unbinding of barstar from wild‐type barnase was compared with dissociation from four charge‐deletion mutants of barnase. Interestingly, we find in all cases that unbinding of barnase and barstar is an uphill process on a smooth, tilted energy landscape. The total free energy difference between the dissociated and bound state was similar for wild‐type barnase–barstar and for the R87A mutant of barnase. The values for the three other mutant barnase mutants K27A, R59A, and R83Q were only about half as much. Besides, we have analyzed the conformational dynamics of important residues at the barnase–barstar interface. In the bound state, their conformational fluctuations are reduced relatively to the free state because of the formation of intermolecular contacts. Interestingly, we find that some residues also show decreased mobility at intermediate stages of the unbinding process suggesting that these residues may be involved in the first contacts being formed on binding. © 2010 Wiley Periodicals, Inc. Biopolymers 93: 977–985, 2010.
Prevalence of the fibrinogen β‐chain, angiotensin‐converting enzyme and plasminogen activator inhibitor‐1 polymorphisms in Costa Rican young adults with thrombotic disease
Authors: Hidalgo Andrea , Salazar‐Sanchez Lizbeth , Cartin Mayra , Mendez Max , Arauz Jorge , Parajeles Alexander
Published: June 2010

Thrombotic disease is a multifactorial condition that involves both classical and genetic risk factors. We studied the association between the classical risk factors of hypertension and smoking, and polymorphisms on the genes of the angiotensin‐converting enzyme (ACE), the β‐chain of fibrinogen (FG), and the plasminogen activator inhibitor‐1 (PAI‐1) in patients with venous and arterial thrombosis. The present investigation is a retrospective case–control study. A total of 340 participants were analyzed, including 162 patients and 178 healthy controls. Hypertension and smoking showed a significant association with thrombotic disease (p < 0.05) but FG level was found significant risk factor only for the venous thrombosis (VT) group (p < 0.04). Significant differences between thrombotic groups were found for the studied polymorphisms of PAI‐1 (p < 0.0014), but for both FG β‐chain gene polymorphisms, none of the molecular analyses showed a positive sample for any mutating allele (p > 0.05). For the ACE polymorphism, the I allele present a protective effect in the general thrombotic group. This is one of the first reports in a Latin‐American population dealing with these molecular markers and thrombotic diseases. Copyright © 2010 John Wiley & Sons, Ltd.
Structure Determination of the Top‐Loop of the Conserved 3′‐Terminal Secondary Structure in the Genome of Flaviviruses
Authors: Lescrinier Eveline , Dyubankova Natalia , Nauwelaerts Koen , Jones Roger , Herdewijn Piet
Published: June 2010

To what extent small differences in RNA sequences (mutations) can have a profound impact on biology remains an intriguing question. This effect can be studied by using untranslated RNA regions as a model. We have studied the influence of mutations on the structure of an RNA hairpin that occurs in the 3′‐untranslated region (UTR) of Flaviviridae, and is known to have a large impact on the vector dependency of flaviviruses. Three related RNA sequences were studied by NMR spectroscopy. The selected sequences represent each one of the three clusters in the flavivirus genes (mosquito‐borne, tick‐borne, and no‐known‐vector viruses). A new strategy was used to obtain chemical shift signatures of carbonyl atoms in unlabeled uridine nucleobases to characterize their involvement in hydrogen bonding. Clear differences occur in the structures and stacking pattern of the three RNA hairpins. The observed differences cannot be predicted based on sequence analysis. A different biology can be correlated with a different RNA tertiary structure. The underlying biological mechanism, however, remains to be studied.
Functions of Genes and Enzymes Involved in Phenalinolactone Biosynthesis
Authors: Daum Martina , Schnell Hans‐Jörg , Herrmann Simone , Günther Andreas , Murillo Renato , Müller Rolf , Bisel Philippe , Müller Michael , Bechthold Andreas
Published: June 2010

Phenalinolactones are novel terpene glycoside antibiotics produced by Streptomyces sp. Tü6071. Inactivation of three oxygenase genes (plaO2, plaO3 and plaO5), two dehydrogenase genes (plaU, plaZ) and one putative acetyltransferase gene (plaV) led to the production of novel phenalinolactone derivatives (PL HS6, PL HS7, PL HS2 and PL X1). Furthermore, the exact biosynthetic functions of two enzymes were determined, and their in vitro activities were demonstrated. PlaO1, an FeII/α‐ketoglutarate‐dependent dioxygenase, is responsible for the key step in γ‐butyrolactone formation, whereas PlaO5, a cytochrome P450‐dependent monooxygenase, catalyses the 1‐C‐hydroxylation of phenalinolactone D. In addition, stable isotope feeding experiments with biosynthetic precursors shed light on the origin of the carbons in the γ‐butyrolactone moiety.
Marine Molecular Machines: Heterocyclization in Cyanobactin Biosynthesis
Authors: McIntosh John A. , Schmidt Eric W.
Published: June 2010

Natural products that contain amino‐acid‐derived (Cys, Ser, Thr) heterocycles are ubiquitous in nature, yet key aspects of their biosynthesis remain undefined. Cyanobactins are heterocyclic ribosomal peptide natural products from cyanobacteria, including symbiotic bacteria living with marine ascidians. In contrast to other ribosomal peptide heterocyclases that have been studied, the cyanobactin heterocyclase is a single protein that does not require an oxidase enzyme. Using this simplifying condition, we provide new evidence to support the hypothesis that these enzymes are molecular machines that use ATP in a product binding or orientation cycle. Further, we show that both protease inhibitors and ATP analogues inhibit heterocyclization and define the order of biochemical steps in the cyanobactin biosynthetic pathway. The cyanobactin pathway enzymes, PatD and TruD, are thiazoline and oxazoline synthetases.
A Zeolite‐Supported Molecular Ruthenium Complex with η6‐C6H6 Ligands: Chemistry Elucidated by Using Spectroscopy and Density Functional Theory
Authors: Ogino Isao , Chen Mingyang , Dyer Jason , Kletnieks Philip W. , Haw James F. , Dixon David A. , Gates Bruce C.
Published: June 2010

An essentially molecular ruthenium–benzene complex anchored at the aluminum sites of dealuminated zeolite Y was formed by treating a zeolite‐supported mononuclear ruthenium complex, [Ru(acac)(η2‐C2H4)2]+ (acac=acetylacetonate, C5H7O2−), with 13C6H6 at 413 K. IR, 13C NMR, and extended X‐ray absorption fine structure (EXAFS) spectra of the sample reveal the replacement of two ethene ligands and one acac ligand in the original complex with one 13C6H6 ligand and the formation of adsorbed protonated acac (Hacac). The EXAFS results indicate that the supported [Ru(η6‐C6H6)]2+ incorporates an oxygen atom of the support to balance the charge, being bonded to the zeolite through three RuO bonds. The supported ruthenium–benzene complex is analogous to complexes with polyoxometalate ligands, consistent with the high structural uniformity of the zeolite‐supported species, which led to good agreement between the spectra and calculations at the density functional theory level. The calculations show that the interaction of the zeolite with the Hacac formed on treatment of the original complex with 13C6H6 drives the reaction to form the ruthenium–benzene complex.
Isomeric Squaraine‐Based [2]Pseudorotaxanes and [2]Rotaxanes: Synthesis, Optical Properties, and Their Tubular Structures in the Solid State
Authors: Xue Min , Su Yong‐Sheng , Chen Chuan‐Feng
Published: June 2010

On the basis of formation of [2]pseudorotaxane complexes between triptycene‐derived tetralactam macrocycles 1 a and 1 b and squaraine dyes, construction of squaraine‐based [2]rotaxanes through clipping reactions were studied in detail. As a result, when two symmetrical squaraines 2 d and 2 e were utilized as templates, two pairs of isomeric [2]rotaxanes 3 a–b and 4 a–b as diastereomers were obtained, owing to the two possible linking modes of triptycene derivatives. It was also found, interestingly, that when a nonsymmetrical dye 2 g was involved, there existed simultaneously three isomers of [2]rotaxanes in one reaction due to the different directions of the guest threading. The 1H NMR and 2D NOESY NMR spectra were used to distinguish the isomers, and the yield of [2]rotaxane 5 a with the benzyl group in the wider rim of the host 1 a was found to be higher than that of another isomer 5 b with an opposite direction of the guest, which indicated the partial selection of the threading direction. The X‐ray structures of 3 b and 4 a showed that, except for the standard hydrogen bonds between the amide protons of the hosts and the carbonyl oxygen atoms of the guests, multiple π⋅⋅⋅π stacking and CH⋅⋅⋅π interactions between triptycene subunits and aromatic rings of the guests also participated in the complexation. Crystallographic studies also revealed that the [2]rotaxane molecules 3 b and 4 a further self‐assembled into tubular structures in the solid state with the squaraine dyes inside the channels. In the case of 4 a, all the nonsymmetrical macrocyclic molecules pointed in one direction, which suggests the formation of oriented tubular structures. Moreover, it was also found that the squaraines encapsulated in the triptycene‐derived macrocycles were protected from chemical attack, and subsequently have potential applications in imaging probes and other biomedical areas.