bluuebunny/crossref_metadata_2025 huggingface dataset:
A TWO-LEVEL QUANTUM SYSTEM IN THE MODULATED OPTICAL FIELD
Authors: JANKAUSKAS ZIGMANTAS
Published: February 2007

Expressions for polarization and population difference of a quantum system in the modulated optical field at the modulation frequency exceeding the transition line width have been obtained in the form of the Fourier series. The characteristic frequency of the system, or the Rabi frequency, has been determined numerically. It depends not only on the intensity of the carrier wave and the detuning magnitude but also on depth and frequency of modulation. The computational technique is applicable both for amplitude and phase modulation.
AN ALGORITHMIC COMPUTATION OF CORRELATION DIMENSION FROM TIME SERIES
Authors: HARIKRISHNAN K. P. , AMBIKA G. , MISRA R.
Published: February 2007

We present an algorithmic scheme to compute the correlation dimension D2 of a time series, without requiring the visual inspection of the scaling region in the correlation sum. It is based on the standard Grassberger–Proccacia [GP] algorithm for computing D2. The scheme is tested using synthetic data sets from several standard chaotic systems as well as by adding noise to low-dimensional chaotic data. We show that the scheme is efficient with a few thousand data points and is most suitable when a nonsubjective comparison of D2 values of two time series is required, such as, in hypothesis testing.
OPTICAL CONDUCTIVITY OF (III, Mn)V DILUTED MAGNETIC SEMICONDUCTORS
Authors: HOANG ANH TUAN , LE DUC ANH
Published: February 2007

The coherent potential approximation (CPA) is used on a minimal model of diluted magnetic semiconductors (DMS), where the carrier feels a nonmagnetic potential at a magnetic impurity site, and its spin interacts with the localized spins of the magnetic impurities through exchange interactions. The CPA equations for one particle Green function are derived and the optical conductivity dependence on the system parameters and temperature is investigated. For illustration, the case of Ga 1-x Mn x As is considered and compared with experimental data.
DECISION TREE SUPPORT VECTOR MACHINE
Authors: ZHANG LI , ZHOU WEI-DA , SU TIAN-TIAN , JIAO LI-CHENG
Published: February 2007

A new multi-class classifier, decision tree SVM (DTSVM) which is a binary decision tree with a very simple structure is presented in this paper. In DTSVM, a problem of multi-class classification is decomposed into a series of ones of binary classification. Here, the binary decision tree is generated by using kernel clustering algorithm, and each non-leaf node represents one binary classification problem. By compared with the other multi-class classification methods based on the binary classification SVMs, the scale and the complexity of DTSVM are less, smaller number of support vectors are needed, and has faster test speed. The final simulation results confirm the feasibility and the validity of DTSVM.
OPTIMIZATION OF BOUNDS IN TEMPORAL FLEXIBLE PLANS WITH DYNAMIC CONTROLLABILITY
Authors: WAH BENJAMIN W. , XIN DONG
Published: February 2007

A temporal flexible planning problem that involves contingent and requirement events can be formulated as a simple temporal network with uncertainty (STNU). An STNU is controllable when there is a strategy for executing the requirement events (or actions) in such a way that all the conditions involving contingent events can be satisfied in all situations. The most interesting and useful controllability property is dynamic controllability in which the remaining actions in an STNU can always be scheduled under all possible feasible durations of future contingent events when all the past contingent events are known. In this paper, we propose and study a novel problem of assigning bounds on the duration of each requirement link in order for the resulting STNU to be dynamically controllable and to minimize the total cost over the allowed durations of all requirement links. We first prove the NP hardness of the problem with a linear cost function. We then formulate the dynamic controllability of an STNU as the constraints in a nonlinear optimization problem. Finally, we present methods for reducing the number of constraints in order to make the problem tractable and to demonstrate the computational performance of our methods.
INTELLIGENT ADAPTIVE CONTROL OF NON-LINEAR SYSTEMS BASED ON EMOTIONAL LEARNING APPROACH
Authors: MEHRABIAN ALI REZA , LUCAS CARO
Published: February 2007

Drawing upon the past research on neuromorphic implementation of an emotionally intelligent control system, a developed version of the brain emotional learning based intelligent controller, BELBIC, is proposed in this paper. The modified system, which essentially realizes direct adaptive control scheme, deals very well for SISO plants, and does not need any pre-training. It is adaptive and robust with respect to changes in the environment since it learns to produce appropriate control actions on-line. An additional advantage of BELBIC is its simplicity as well as low computational load. The performance of the system is demonstrated via application on previously studied benchmarks involving optimization and adaptive control in nonlinear systems with MLP-backpropagation (BP) nets.
EVOLVING THE UPDATE STRATEGY OF THE PARTICLE SWARM OPTIMISATION ALGORITHMS
Authors: DIOŞAN LAURA , OLTEAN MIHAI
Published: February 2007

A complex model for evolving the update strategy of a Particle Swarm Optimisation (PSO) algorithm is described in this paper. The model is a hybrid technique that combines a Genetic Algorithm (GA) and a PSO algorithm. Each GA chromosome is an array encoding a meaning for updating the particles of the PSO algorithm. The Evolved PSO algorithm is compared to several human-designed PSO algorithms by using ten artificially constructed functions and one real-world problem. Numerical experiments show that the Evolved PSO algorithm performs similarly and sometimes even better than the Standard approaches for the considered problems. The Evolved PSO is highly scalable (regarding the size of the problem's input), being able to solve problems having different dimensions.
ANALYSIS OF MULTIDIMENSIONAL XOR CLASSIFICATION PROBLEM WITH EVOLUTIONARY FEEDFORWARD NEURAL NETWORKS
Authors: MANGAL MANISH , SINGH MANU PRATAP
Published: February 2007

This paper describes the application of two evolutionary algorithms to the feedforward neural networks used in classification problems. Besides of a simple backpropagation feedforward algorithm, the paper considers the genetic algorithm and random search algorithm. The objective is to analyze the performance of GAs over the simple backpropagation feedforward in terms of accuracy or speed in this problem. The experiments considered a feedforward neural network trained with genetic algorithm/random search algorithm and 39 types of network structures and artificial data sets. In most cases, the evolutionary feedforward neural networks seemed to have better of equal accuracy than the original backpropagation feedforward neural network. We found few differences in the accuracy of the networks solved by applying the EAs, but found ample differences in the execution time. The results suggest that the evolutionary feedforward neural network with random search algorithm might be the best algorithm on the data sets we tested.
A NEW SENTENCE REDUCTION TECHNIQUE BASED ON A DECISION TREE MODEL
Authors: NGUYEN LE MINH , PHAN XUAN HIEU , HORIGUCHI SUSUMU , SHIMAZU AKIRA
Published: February 2007

This paper addresses a novel sentence reduction algorithm based on a decision tree model in which semantic information is used to enhance the accuracy of sentence reduction. The proposed algorithm is able to deal with the changeable order problem in sentence reduction. Furthermore, the use of decision list to solve the fragment problem in sentence reduction based decision tree model is also discussed. Our experimental results show an improvement when compared with earlier methods.
SEIFERT MATRICES OF PERIODIC KNOTS
Authors: KO KI HYOUNG , SONG WON TAEK
Published: February 2007

We characterize the Seifert matrices of periodic knots in S3 up to S-equivalence. Given a periodic knot we construct an equivariant spanning surface F and choose a basis for H1(F) in such a way that the Seifert matrix has a special form exhibiting the periodicity. Conversely, given such a Seifert matrix we construct a periodic knot that realizes it. We exhibit the decomposition of H1(F;ℂ) into eigenspaces of the periodic action, orthogonal to each other with respect to the Seifert pairing. Consequently we obtain Murasugi's formula for the Alexander polynomial of the periodic knot.
ON THE KAUFFMAN BRACKET SKEIN MODULE OF THE QUATERNIONIC MANIFOLD
Authors: GILMER PATRICK M. , HARRIS JOHN M.
Published: February 2007

We use recoupling theory to study the Kauffman bracket skein module of the quaternionic manifold over ℤ[A±1] localized by inverting all the cyclotomic polynomials. We prove that the skein module is spanned by five elements. Using the quantum invariants of these skein elements and the ℤ2-homology of the manifold, we determine that they are linearly independent.
ON THE FORMAL ANALYSIS OF THE DYNAMICS OF SIMULATED AGENT SOCIETIES
Authors: EIBEN A. E. , JONKER C. M. , POPOVA V. , SCHUT M. C.
Published: February 2007

To analyze emergent behavior, a formal framework is needed to characterize the structure and dynamics of complex interaction-based multi-agent systems. We introduce an extension of an existing agent testbed for artificial societies making it possible to formally analyze the dynamics of the simulated agent system. The extension generates temporally annotated logical terms that describe parts of the dynamics of the simulated system. Based on these terms, it is possible to validate hypotheses about the system on different levels of aggregation, i.e. agent, group and system level. We present first results from a set of simple experiments in a class of artificial societies.
ALTRUISM AMONG SIMPLE AND SMART VAMPIRES
Authors: DI TOSTO GENNARO , PAOLUCCI MARIO , CONTE ROSARIA
Published: February 2007

In this work, we present a simulation study drawn upon a famous ethological example: food-sharing habit of vampire bats in Central America. A norm of reciprocity is introduced when agents are expected to exhibit a cooperative behavior under serious environmental strictures (infrequent but lethal food scarcity). We compare different agents' architectures (with different levels of cognitive complexity) in the evolution of food-sharing habit and we analyze their performances against the presence of cheaters in the population. The experiments are aimed at studying the role of cognitive mediators (i.e. goals) in spreading altruism, described as a purposeful action.
INSTITUTIONAL REALITY AND NORMS: SPECIFYING AND MONITORING AGENT ORGANIZATIONS
Authors: CARDOSO HENRIQUE LOPES , OLIVEIRA EUGÉNIO
Published: February 2007

Norms and institutions have been proposed to regulate multi-agent interactions. However, agents are intrinsically autonomous, and may thus decide whether to comply with norms. On the other hand, besides institutional norms, agents may adopt new norms by establishing commitments with other agents. In this paper, we address these issues by considering an electronic institution that monitors the compliance to norms in an evolving normative framework: norms are used both to regulate an existing environment and to define contracts that make agents' commitments explicit. In particular, we consider the creation of virtual organizations in which agents commit to certain cooperation efforts regulated by appropriate norms. The supervision of norm fulfillment is based on the notion of institutional reality, which is constructed by assigning powers to agents enacting institutional roles. Constitutive rules make a connection between the illocutions of those agents and institutional facts, certifying the occurrence of associated external transactions. Contract specification is based on conditional prescription of obligations. Contract monitoring relies on rules for detecting the fulfillment and violation of those obligations. The implementation of our normative institutional environment is supported by a rule-based inference engine.
NORM NEGOTIATION IN MULTIAGENT SYSTEMS
Authors: BOELLA GUIDO , VAN DER TORRE LEENDERT
Published: February 2007

Normative multiagent systems provide agents with abilities to autonomously devise societies and organizations coordinating their behavior via social norms and laws. In this paper, we study how agents negotiate new social norms and when they accept them. We introduce a negotiation model based on what we call the social delegation cycle, which explains the negotiation of new social norms from agent desires in three steps. First, individual agents or their representatives negotiate social goals, then a social goal is negotiated in a social norm, and finally the social norm is accepted by the agents when it leads to fulfillment of the desires the cycle started with. We characterize the allowed proposals during social goal negotiation as mergers of the individual agent desires, and we characterize the allowed proposals during norm negotiation as both joint plans to achieve the social goal (obligations associated with the norm) and the associated sanctions or rewards (a control system associated with the norm). The norm is accepted when the norm is stable in the sense that agents will act according to the norm, and effective in the sense that fulfillment of the norm leads to achievement of the agents' desires. We also compare norm negotiation with contract negotiation and negotiation of the distribution of obligations.
ON THE CONVERGENCE STRUCTURE OF L-TOPOLOGICAL SPACES AND THE CONTINUITY IN L-TOPOLOGICAL SPACES
Authors: DEMİRCİ MUSTAFA
Published: February 2007

A general and a comprehensive theory of fuzzy topological spaces on the basis of a fixed quadruple M = (L, ≤, ⊗, *), where (L, ≤), ⊗ and *, respectively, denote a complete lattice and binary operations on L satisfying some further axioms, was introduced by Höhle and Šostak. L-topological spaces, convergence structure of L-topological spaces and L-continuous functions form an important part of their work. The present paper continues the study in this area, and provides new results on the convergence structure of L-topological spaces and the continuity in L-topological spaces.
DELAY-DEPENDENT GLOBAL ROBUST ASYMPTOTIC STABILITY ANALYSIS OF BAM NEURAL NETWORKS WITH TIME DELAY: AN LMI APPROACH
Authors: LOU XU-YANG , CUI BAO-TONG
Published: February 2007

The global robust asymptotic stability of bi-directional associative memory (BAM) neural networks with constant or time-varying delays is studied. An approach combining the Lyapunov-Krasovskii functional with the linear matrix inequality (LMI) is taken to study the problem. Some a criteria for the global robust asymptotic stability, which gives information on the delay-dependent property, are derived. Some illustrative examples are given to demonstrate the effectiveness of the obtained results.
REVERSE ENGINEERING OF THE NK BOOLEAN NETWORK AND ITS EXTENSION — FUZZY LOGIC NETWORK
Authors: CAO YINGJUN , WANG PAUL P. , RESCONI GERMANO
Published: February 2007

In this paper, we first propose a reverse engineering solution to decode the NK Boolean dynamic network given the input and output of the system. This theory utilizes basis functions and dynamic matrices, through which the network's evolutionary behavior can be simulated in a rigorous mathematical manner. Then, a general network model, fuzzy logic network (FLN), is presented as the extension of the Boolean network. This novel network model assigns variable values in a continuous domain, and it can accommodate internal conflicts among variables. In addition, the FLN uses fuzzy logical functions instead of Boolean logical functions, which enables it to model highly non-linear relationships and periodicity. Using the approach of annealed approximations, we proved important theorems concerning the dynamic property of the FLN. Combined with the Zipf's law, the criteria of applying FLN to the modeling of gene regulatory networks were achieved.
A CREDIT EVALUATION IN E-BUSINESS THROUGH GAME THEORY
Authors: LIU XIAOHONG , RUAN DA , LI TIANRUI
Published: February 2007

The security of both technical and trade credit factors becomes a serious bottleneck that affects the current development of e-business. Honest behavior is one of the important aspects of trade credit safety. It is a vital step to establish and maintain a safe credit system. In this paper, we analyze the characteristic of the credit in e-business and establish a motivation model that violates honest behavior in e-business. We evaluate the credit, the mode of evaluation and the behavior of the credit in e-business by using game theory. We present the factors that affect the justness of credit evaluation in e-business.
AN INTELLIGENT CLASSIFICATION METHOD IN BANK CUSTOMER RELATIONSHIP MANAGEMENT
Authors: ZHANG JIE , LU JIE , ZHANG GUANGQUAN
Published: February 2007

Customer classification is one of the major tasks in customer relationship management. Customers often have both static characteristics and dynamic behavioral features. Using both kinds of data to conduct comprehensive analysis can enhance the reasonability of customer classification. In the proposed classification method, customer dynamic data is clustered using a hybrid genetic algorithm. The result is then combined with customer static data to give reasonable customer segmentation supported by neural network technique. A bank dataset-based experiment shows that applying the proposed method can obviously improve the accuracy of customer classification comparing with the traditional methods where only static data is used.
INTEGRATION OF HOSPITAL INFORMATION SYSTEMS IN CHINA
Authors: FANG MEIQI , ZHANG YUAN , ZHAO HOUFANG , WU NING , YU JIA
Published: February 2007

Information sharing and the conformity of information systems in China's hospitals have drawn attention due to the rapid development of the medicine industry and medical information systems. The paper proposes a game theory-based model for information sharing in hospitals by analyzing the current situation in China. Using the proposed model, a Doctor Workstation System (DWS) is developed. This DWS implements the conformity of the medical information systems by applying semantic web and web service techniques. The results show that the conformity of information systems for hospitals is a trend for the medical informalization in China.
Leaf Senescence
Authors: Lim Pyung Ok , Kim Hyo Jung , Gil Nam Hong
Published: February 2007

Leaf senescence constitutes the final stage of leaf development and is critical for plants’ fitness as nutrient relocation from leaves to reproducing seeds is achieved through this process. Leaf senescence involves a coordinated action at the cellular, tissue, organ, and organism levels under the control of a highly regulated genetic program. Major breakthroughs in the molecular understanding of leaf senescence were achieved through characterization of various senescence mutants and senescence-associated genes, which revealed the nature of regulatory factors and a highly complex molecular regulatory network underlying leaf senescence. The genetically identified regulatory factors include transcription regulators, receptors and signaling components for hormones and stress responses, and regulators of metabolism. Key issues still need to be elucidated, including cellular-level analysis of senescence-associated cell death, the mechanism of coordination among cellular-, organ-, and organism-level senescence, the integration mechanism of various senescence-affecting signals, and the nature and control of leaf age.
Plant ATP-Binding Cassette Transporters
Authors: Rea Philip A.
Published: February 2007

The ATP-binding cassette (ABC) protein superfamily is one of the largest known, with over 120 members in both Arabidopsis thaliana and rice (Oryza sativa). Most, but not all, ABC proteins are modularly organized membrane proteins (“ABC transporters”) that mediate MgATP-energized transmembrane transport and/or regulate other transporters. The range of processes in which members of the various subclasses of plant ABC transporters have been implicated encompasses polar auxin transport, lipid catabolism, xenobiotic detoxification, disease resistance, and stomatal function. Although it is often possible to predict the likely function of a plant ABC transporter on the basis of its subfamily membership, there are many whose capabilities deviate from what would be predicted from the properties of even their most sequence-related counterparts. When taking account of this and the disparate processes in which the few that have been characterized participate, it is likely that elucidation of the mechanistic basis of any given plant process will necessitate consideration of at least one ABC transporter.
Light Regulation of Stomatal Movement
Authors: Shimazaki Ken-ichiro , Doi Michio , Assmann Sarah M. , Kinoshita Toshinori
Published: February 2007

Stomatal pores, each surrounded by a pair of guard cells, regulate CO2 uptake and water loss from leaves. Stomatal opening is driven by the accumulation of K+ salts and sugars in guard cells, which is mediated by electrogenic proton pumps in the plasma membrane and/or metabolic activity. Opening responses are achieved by coordination of light signaling, light-energy conversion, membrane ion transport, and metabolic activity in guard cells. In this review, we focus on recent progress in blue- and red-light-dependent stomatal opening. Because the blue-light response of stomata appears to be strongly affected by red light, we discuss underlying mechanisms in the interaction between blue-light signaling and guard cell chloroplasts.
Alternative Splicing of Pre-Messenger RNAs in Plants in the Genomic Era
Authors: Reddy Anireddy S.N.
Published: February 2007

Primary transcripts (precursor-mRNAs) with introns can undergo alternative splicing to produce multiple transcripts from a single gene by differential use of splice sites, thereby increasing the transcriptome and proteome complexity within and between cells and tissues. Alternative splicing in plants is largely an unexplored area of gene expression, as this phenomenon used to be considered rare. However, recent genome-wide computational analyses have revealed that alternative splicing in flowering plants is far more prevalent than previously thought. Interestingly, pre-mRNAs of many spliceosomal proteins, especially serine/arginine-rich (SR) proteins, are extensively alternatively spliced. Furthermore, stresses have a dramatic effect on alternative splicing of pre-mRNAs including those that encode many spliceosomal proteins. Although the mechanisms that regulate alternative splicing in plants are largely unknown, several reports strongly suggest a key role for SR proteins in spliceosome assembly and regulated splicing. Recent studies suggest that alternative splicing in plants is an important posttranscriptional regulatory mechanism in modulating gene expression and eventually plant form and function.
The Production of Unusual Fatty Acids in Transgenic Plants
Authors: Napier Johnathan A.
Published: February 2007

The ability to genetically engineer plants has facilitated the generation of oilseeds synthesizing non-native fatty acids. Two particular classes of fatty acids are considered in this review. First, so-called industrial fatty acids, which usually contain functional groups such as hydroxyl, epoxy, or acetylenic bonds, and second, very long chain polyunsaturated fatty acids normally found in fish oils and marine microorgansims. For industrial fatty acids, there has been limited progress toward obtaining high-level accumulation of these products in transgenic plants. For very long chain polyunsaturated fatty acids, although they have a much more complex biosynthesis, accumulation of some target fatty acids has been remarkably successful. In this review, we consider the probable factors responsible for these different outcomes, as well as the potential for further optimization of the transgenic production of unusual fatty acids in transgenic plants.
Genetic and Epigenetic Mechanisms for Gene Expression and Phenotypic Variation in Plant Polyploids
Authors: Chen Z. Jeffrey
Published: February 2007

Polyploidy, or whole-genome duplication (WGD), is an important genomic feature for all eukaryotes, especially many plants and some animals. The common occurrence of polyploidy suggests an evolutionary advantage of having multiple sets of genetic material for adaptive evolution. However, increased gene and genome dosages in autopolyploids (duplications of a single genome) and allopolyploids (combinations of two or more divergent genomes) often cause genome instabilities, chromosome imbalances, regulatory incompatibilities, and reproductive failures. Therefore, new allopolyploids must establish a compatible relationship between alien cytoplasm and nuclei and between two divergent genomes, leading to rapid changes in genome structure, gene expression, and developmental traits such as fertility, inbreeding, apomixis, flowering time, and hybrid vigor. Although the underlying mechanisms for these changes are poorly understood, some themes are emerging. There is compelling evidence that changes in DNA sequence, cis- and trans-acting effects, chromatin modifications, RNA-mediated pathways, and regulatory networks modulate differential expression of homoeologous genes and phenotypic variation that may facilitate adaptive evolution in polyploid plants and domestication in crops.
Oxidative Modifications to Cellular Components in Plants
Authors: Møller Ian M. , Jensen Poul Erik , Hansson Andreas
Published: February 2007

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are produced in many places in living cells and at an increased rate during biotic or abiotic stress. ROS and RNS participate in signal transduction, but also modify cellular components and cause damage. We first look at the most common ROS and their properties. We then consider the ways in which the cell can regulate their production and removal. We critically assess current knowledge about modifications of polyunsaturated fatty acids (PUFAs), DNA, carbohydrates, and proteins and illustrate this knowledge with case stories wherever possible. Some oxidative breakdown products, e.g., from PUFA, can cause secondary damage. Other oxidation products are secondary signaling molecules. We consider the fate of the modified components, the energetic costs to the cell of replacing such components, as well as strategies to minimize transfer of oxidatively damaged components to the next generation.
Regulation of Cullin RING Ligases
Authors: Hotton Sara K. , Callis Judy
Published: February 2007

The ubiquitin/26S proteasome pathway largely mediates selective proteolysis in the nucleus and cytosol. This pathway catalyzes covalent attachment of ubiquitin (UBQ) to substrate proteins in an E1-E2-E3 cascade. Ubiquitin E3 ligases interact with substrates to catalyze UBQ transfer from E2 to substrate. Within the E3 ligase superfamily, cullin RING ligases (CRLs) are significant in plants because they are linked to hormonal signaling, developmental programs, and environmental responses. Thus, knowledge of CRL regulation is required for a complete understanding of these processes. A major mechanism modulating CRL activity is modification of the cullin subunit by RUB (RELATED TO UBIQUITIN), a ubiquitin-like protein, and demodification by the COP9 signalosome (CSN). CULLIN-ASSOCIATED NEDD8-DISSOCIATED 1 (CAND1) interacts with CRLs, affecting both rubylation and derubylation. Described here are the pathways, regulation, and biological function of rubylation and derubylation, as well as future directions and outstanding questions.
Stomatal Development
Authors: Bergmann Dominique C. , Sack Fred D.
Published: February 2007

Stomata are cellular epidermal valves in plants central to gas exchange and biosphere productivity. The pathways controlling their formation are best understood for Arabidopsis thaliana where stomata are produced through a series of divisions in a dispersed stem cell compartment. The stomatal pathway is an accessible system for analyzing core developmental processes including position-dependent patterning via intercellular signaling and the regulation of the balance between proliferation and cell specification. This review synthesizes what is known about the mechanisms and genes underlying stomatal development. We contrast the functions of genes that act earlier in the pathway, including receptors, kinases, and proteases, with those that act later in the cell lineage. In addition, we discuss the relationships between environmental signals, stomatal development genes, and the capacity for controlling shoot gas exchange.
Zinc deficiency depresses p21 gene expression: inhibition of cell cycle progression is independent of the decrease in p21 protein level in HepG2 cells
Authors: Wong Stephen H. K. , Zhao Yangqing , Schoene Norberta W. , Han Chung-Ting , Shih Rita S. M. , Lei Kai Y.
Published: February 2007

The influence of zinc status on p21 gene expression was examined in human hepatoblastoma (HepG2) cells. Cells were cultured for one passage in a basal medium depleted of zinc to induce severely zinc-deficient (ZD) cells or in basal medium supplemented with 0.4, 4.0, 16, or 32 μM zinc to represent mild zinc deficiency (ZD0.4), the amount of zinc in most normal media (ZN), the normal human plasma zinc level (zinc-adequate; ZA), or the high end of plasma zinc attainable by oral supplementation (ZS), respectively. In ZD and ZD0.4 cells, the nuclear p21 protein level, mRNA abundance, and promoter activity were reduced to 40, 70, and 65%, respectively, of ZN cells. However, p21 protein and mRNA levels, as well as p21 promoter activity, were not altered in ZA and ZS cells compared with ZN cells. Moreover, the amounts of acetylated histone-4 associated with the proximal and distal p21 promoter regions, as a measure of p21 promoter accessibility, were decreased in ZD (73 and 64%, respectively) and ZD0.4 (82 and 77%, respectively) cells compared with ZN cells (100 and 100%, respectively). Thus multiple lines of evidence indicate that the transcriptional process of p21 is downregulated by depressed zinc status in HepG2 cells. Furthermore, the transfection of 5 μg of plasmid cytomegalovirus-p21 plasmid, which constitutively expressed p21, was able to normalize the reduction in p21 protein level and cyclin D1-cdk4 complex activity but not the inhibition of cell growth and G1/S cell cycle progression in ZD cells.
Reduced inflammatory response and increased microcirculatory disturbances during hepatic ischemia-reperfusion injury in steatotic livers of ob/ob mice
Authors: Hasegawa Tadashi , Ito Yoshiya , Wijeweera Jayanthika , Liu Jie , Malle Ernst , Farhood Anwar , McCuskey Robert S. , Jaeschke Hartmut
Published: February 2007

Steatosis is a major risk factor for complications after liver surgery. Since neutrophil cytotoxicity is critical for ischemia-reperfusion injury in normal livers, the aim of the present study was to evaluate whether an exaggerated inflammatory response could cause the increased injury in steatotic livers. In C57Bl/6 mice, 60 min of warm hepatic ischemia triggered a gradual increase in hepatic neutrophil accumulation during reperfusion with peak levels of 100-fold over baseline at 12 h of reperfusion. Neutrophil extravasation and a specific neutrophil-induced oxidant stress (immunostaining for hypochlorous acid-modified epitopes) started at 6 h of reperfusion and peaked at 12–24 h. Ob/ob mice, which had a severe macrovesicular steatosis, suffered significantly higher injury (alanine transaminase activity: 18,000 ± 2,100 U/l; 65% necrosis) compared with lean littermates (alanine transaminase activity: 4,900 ± 720 U/l; 24% necrosis) at 6 h of reperfusion. However, 62% fewer neutrophils accumulated in steatotic livers. This correlated with an attenuated increase in mRNA levels of several proinflammatory genes in ob/ob mice during reperfusion. In contrast, sham-operated ob/ob mice had a 50% reduction in liver blood flow and 35% fewer functional sinusoids compared with lean littermates. These deficiencies in liver blood flow and the microcirculation were further aggravated only in ob/ob mice during reperfusion. The attenuated inflammatory response and reduced neutrophil-induced oxidant stress observed in steatotic livers during reperfusion cannot be responsible for the dramatically increased injury in ob/ob mice. In contrast, the aggravated injury appears to be mediated by ischemic necrosis due to massive impairment of blood and oxygen supply in the steatotic livers.
Quantitative imaging of lymph function
Authors: Sharma Ruchi , Wang Wei , Rasmussen John C. , Joshi Amit , Houston Jessica P. , Adams Kristen E. , Cameron Arlin , Ke Shi , Kwon Sunkuk , Mawad Michel E. , Sevick-Muraca Eva M.
Published: February 2007

Functional lymphatic imaging was demonstrated in the abdomen and anterior hindlimb of anesthetized, intact Yorkshire swine by using near-infrared (NIR) fluorescence imaging following intradermal administration of 100–200 μl of 32 μM indocyanine green (ICG) and 64 μM hyaluronan NIR imaging conjugate to target the lymph vacular endothelial receptor (LYVE)-1 on the lymph endothelium. NIR fluorescence imaging employed illumination of 780 nm excitation light (∼2 mW/cm2) and collection of 830 nm fluorescence generated from the imaging agents. Our results show the ability to image the immediate trafficking of ICG from the plexus, through the vessels and lymphangions, and to the superficial mammary, subiliac, and middle iliac lymph nodes, which were located as deep as 3 cm beneath the tissue surface. “Packets” of ICG-transited lymph vessels of 2–16 cm length propelled at frequencies of 0.5–3.3 pulses/min and velocities of 0.23–0.75 cm/s. Lymph propulsion was independent of respiration rate. In the case of the hyaluronan imaging agent, lymph propulsion was absent as the dye progressed immediately through the plexus and stained the lymph vessels and nodes. Lymph imaging required 5.0 and 11.9 μg of ICG and hyaluronan conjugate, respectively. Our results suggest that microgram quantities of NIR optical imaging agents and their conjugates have a potential to image lymph function in patients suffering from lymph-related disorders.
Heterogeneous ventricular chamber response to hypokalemia and inward rectifier potassium channel blockade underlies bifurcated T wave in guinea pig
Authors: Poelzing Steven , Veeraraghavan Rengasayee
Published: February 2007

It was previously demonstrated that transmural electrophysiological heterogeneities can inscribe the ECG T wave. However, the bifurcated T wave caused by loss of inward rectifier potassium current ( IK1) function is not fully explained by transmural heterogeneities. Since right ventricular (RV) guinea pig myocytes have significantly lower IK1 than left ventricular (LV) myocytes, we hypothesized that the complex ECG can be inscribed by heterogeneous chamber-specific responses to hypokalemia and partial IK1 blockade. Ratiometric optical action potentials were recorded from the epicardial surface of the RV and LV. BaCl2 (10 μmol/l) was perfused to partially block IK1 in isolated guinea pig whole heart preparations. BaCl2 or hypokalemia alone significantly increased RV basal (RVB) action potential duration (APD) by ∼30% above control compared with LV apical (LVA) APD (14%, P < 0.05). In the presence of BaCl2, 2 mmol/l extracellular potassium (hypokalemia) further increased RVB APD to a greater extent (31%) than LVA APD (19%, P < 0.05) compared with BaCl2 perfusion alone. Maximal dispersion between RVB and LVA APD increased by 105% ( P < 0.05), and the QT interval prolonged by 55% ( P < 0.05) during hypokalemia and BaCl2. Hypokalemia and BaCl2 produced an ECG with a double repolarization wave. The first wave (QT1) corresponded to selective depression of apical LV plateau potentials, while the second wave (QT2) corresponded to the latest repolarizing RVB myocytes. These data suggest that final repolarization is more sensitive to extracellular potassium changes in regions with reduced IK1, particularly when IK1 availability is reduced. Furthermore, underlying IK1 heterogeneities can potentially contribute to the complex ECG during IK1 loss of function and hypokalemia.
Electrophysiological study on the effects of leptin in rat dorsal motor nucleus of the vagus
Authors: Li Tzu-Ling , Chiou Lih-Chu , Lin You Shuei , Hsieh Jing-Ru , Hwang Ling-Ling
Published: February 2007

Immunoreactivity of leptin receptor (Ob-R) has been detected in rat dorsal motor nucleus of the vagus (DMNV). Here, we confirmed the presence of Ob-R immunoreactivity on retrograde-labeled parasympathetic preganglionic neurons in the DMNV of neonatal rats. The present study investigated the effects of leptin on DMNV neurons, including parasympathetic preganglionic neurons, by using whole cell patch-clamp recording technique in brain stem slices of neonatal rats. Leptin (30–300 nM) induced membrane depolarization and hyperpolarization, respectively, in 14 and 15 out of 80 DMNV neurons tested. Both leptin-induced inward and outward currents persisted in the presence of TTX, indicating that leptin affected DNMV neurons postsynaptically. The current-voltage (I–V) curve of leptin-induced inward currents is characterized by negative slope conductance and has an average reversal potential of −90 ± 3 mV. The reversal potential of the leptin-induced inward current was shifted to a more positive potential level in a high-potassium medium. These results indicate that a decrease in potassium conductance is likely the main ionic mechanism underlying the leptin-induced depolarization. On the other hand, the I–V curve of leptin-induced outward currents is characterized by positive slope conductance and has an average reversal potential of −88 ± 3 mV, suggesting that an increase in potassium conductance may underlie leptin-induced hyperpolarization. Most of the leptin-responsive DMNV neurons were identified as being parasympathetic preganglionic neurons. These results suggest that the DMNV is one of the central target sites of leptin, and leptin can regulate parasympathetic outflow from the DMNV by directly acting on the parasympathetic preganglionic neurons of the DMNV.
Insulin resistance and impaired baroreflex gain during pregnancy
Authors: Daubert Daisy L. , Chung Mee-Young , Brooks Virginia L.
Published: February 2007

Pregnancy decreases baroreflex gain, but the underlying mechanism is unclear. Insulin resistance, which has been associated with reduced transport of insulin into the brain, is a consistent feature of many conditions exhibiting impaired baroreflex gain, including pregnancy. Therefore, using conscious pregnant and nonpregnant rabbits, we tested the novel hypothesis that the pregnancy-induced impairment in baroreflex gain is due to insulin resistance and reduced brain insulin. Baroreflex gain was determined by quantifying changes in heart rate in response to stepwise steady-state changes in arterial pressure, secondary to infusion of nitroprusside and phenylephrine. We found that insulin sensitivity and baroreflex gain were strongly correlated in nonpregnant and term pregnant rabbits ( r2 = 0.59). The decrease in insulin sensitivity and in baroreflex gain exhibited similar time courses throughout pregnancy, reaching significantly lower levels at 3 wk of gestation and remaining reduced at 4 wk (term is 31 days). Treatment of rabbits with the insulin-sensitizing drug rosiglitazone during pregnancy almost completely normalized baroreflex gain. Finally, pregnancy significantly lowered cerebrospinal fluid insulin concentrations. These data identify insulin resistance as a mechanism underlying pregnancy-induced baroreflex impairment and suggest, for the first time in any condition, that decreased brain insulin concentrations may be the link between reductions in peripheral insulin sensitivity and baroreflex gain.
Myofibrillar protein oxidation and contractile dysfunction in hyperthyroid rat diaphragm
Authors: Yamada Takashi , Mishima Takaaki , Sakamoto Makoto , Sugiyama Minako , Matsunaga Satoshi , Wada Masanobu
Published: February 2007

The purpose of the present study was to test the hypothesis that administration of thyroid hormone [3,5,3′-triiodo-l-thyronine (T3)] could result in oxidation of myofibrillar proteins and, in turn, induce alterations in respiratory muscle function. Daily injection of T3 for 21 days depressed isometric forces of diaphragm fiber bundles across a range of stimulus frequencies (1, 10, 20, 40, 75, and 100 Hz) ( P < 0.05). These reductions in force production were accompanied by a remarkable increment (104%; P < 0.05) in carbonyl groups of myofibrillar proteins. In contrast, T3 treatment has no effects on the carbonyl content in myosin heavy chain. In additional experiments, we have also tested the efficacy of carvedilol, a nonselective β1- β2-blocker that possesses antioxidative properties. Treatment with carvedilol dramatically improved isometric tetanic force production at stimulus frequencies from 40 to 100 Hz ( P < 0.05). Carvedilol also prevented T3-induced contractile protein oxidation ( P < 0.05). These data suggest that the oxidative modification of myofibrillar proteins may account, at least in part, for an impairment of diaphragm in hyperthyroidism.
Tectal Control of Locomotion, Steering, and Eye Movements in Lamprey
Authors: Saitoh Kazuya , Ménard Ariane , Grillner Sten
Published: February 2007

The intrinsic function of the brain stem–spinal cord networks eliciting the locomotor synergy is well described in the lamprey—a vertebrate model system. This study addresses the role of tectum in integrating eye, body orientation, and locomotor movements as in steering and goal-directed behavior. Electrical stimuli were applied to different areas within the optic tectum in head-restrained semi-intact lampreys ( n = 40). Motions of the eyes and body were recorded simultaneously (videotaped). Brief pulse trains (<0.5 s) elicited only eye movements, but with longer stimuli (>0.5 s) lateral bending movements of the body (orientation movements) were added, and with even longer stimuli locomotor movements were initiated. Depending on the tectal area stimulated, four characteristic response patterns were observed. In a lateral area conjugate horizontal eye movements combined with lateral bending movements of the body and locomotor movements were elicited, depending on stimulus duration. The amplitude of the eye movement and bending movements was site specific within this region. In a rostromedial area, bilateral downward vertical eye movements occurred. In a caudomedial tectal area, large-amplitude undulatory body movements akin to struggling behavior were elicited, combined with large-amplitude eye movements that were antiphasic to the body movements. The alternating eye movements were not dependent on vestibuloocular reflexes. Finally, in a caudolateral area locomotor movements without eye or bending movements could be elicited. These results show that tectum can provide integrated motor responses of eye, body orientation, and locomotion of the type that would be required in goal-directed locomotion.
p38-Mediated Inactivation of Cyclin D1/Cyclin-Dependent Kinase 4 Stimulates Nucleolar Translocation of RelA and Apoptosis in Colorectal Cancer Cells
Authors: Thoms Hazel C. , Dunlop Malcolm G. , Stark Lesley A.
Published: February 2007

Aberrant nuclear factor-κB (NF-κB) signaling plays a role in cancer initiation and progression; thus, it represents a potential therapeutic target. We previously identified a mechanism of repression of NF-κB transcriptional activity and induction of apoptosis in colon cancer cells involving nuclear/nucleolar translocation of the RelA (p65) component of NF-κB. This response was stimulated by cellular stress-inducing agents, including aspirin, but not by tumor necrosis factor. Here, we investigate the upstream molecular mechanisms responsible for nucleolar targeting of RelA and show that aspirin activates the p38 mitogen-activated protein kinase (MAPK) pathway in colorectal cancer cells. We also show that aspirin causes rapid, ubiquitin-dependent degradation of cyclin D1, a known p38 target. Aspirin-induced p38 activation preceded cyclin D1 degradation, which was then followed by activation of the NF-κB pathway, suggesting a causative link. Indeed, chemical p38 inhibition (PD169316) and small interfering RNA directed against p38 blocked aspirin-induced cyclin D1 degradation, nucleolar translocation of RelA, and apoptosis. Furthermore, chemical inhibition of the cyclin D1/cyclin-dependent kinase 4 (CDK4) kinase complex, used as a surrogate for cyclin D1 degradation, caused nucleolar translocation of RelA, repression of κB-driven transcription, and apoptosis, thereby reproducing the effects of aspirin. In addition, we found that aspirin and the CDK4 inhibitor induced nucleolar translocation of RelA and apoptosis through a common mechanism involving the NH2-terminal nucleolar localization signal. Collectively, these data suggest that aspirin causes inhibition of cyclin D1/CDK4 through the p38 MAPK pathway. This inhibition stimulates the NF-κB pathway to induce nucleolar translocation of RelA and apoptosis. These novel findings have considerable relevance to the rational design of novel chemotherapeutic and chemopreventative strategies. [Cancer Res 2007;67(4):1660–9]
c-Met Overexpression Is a Prognostic Factor in Ovarian Cancer and an Effective Target for Inhibition of Peritoneal Dissemination and Invasion
Authors: Sawada Kenjiro , Radjabi A. Reza , Shinomiya Nariyoshi , Kistner Emily , Kenny Hilary , Becker Amy R. , Turkyilmaz Muge A. , Salgia Ravi , Yamada S. Diane , Vande Woude George F. , Tretiakova Maria S. , Lengyel Ernst
Published: February 2007

The hepatocyte growth factor receptor c-Met is a receptor tyrosine kinase that plays an important role in tumor growth by activating mitogenic signaling pathways. The goal of this study was to evaluate the role of c-Met in the biology of ovarian cancer and to determine its potential as a therapeutic target. c-Met protein expression was detected by immunohistochemistry in 138 advanced-stage ovarian cancers using a tissue microarray annotated with disease-specific patient follow-up. Fifteen of 138 (11%) tissues had c-Met overexpression. Median survival for patients with high c-Met levels was 17 months versus 32 months (P = 0.001) for patients with low c-Met expression. Infection of SKOV-3ip1 cells with an adenovirus expressing a small interfering RNA (siRNA) against c-Met efficiently inhibited c-Met protein and mRNA expression as well as extracellular signal-regulated kinase and phosphatidylinositol 3-kinase signaling. It also inhibited adhesion to different extracellular matrix components, human primary mesothelial cells, and full-thickness human peritoneum and, in vivo, to mouse peritoneum. This was paralleled by a significant reduction in α5 and β1 integrin protein and mRNA expression as well as a reduction of urokinase and matrix metalloproteinase (MMP)-2/MMP-9 activity. In SKOV-3ip1 ovarian cancer xenografts, i.p. treatment with the c-Met siRNA significantly reduced tumor burden, ascites formation, protease activity, and the number of peritoneal implants but not tumor size or angiogenesis. These results suggest that c-Met overexpression is a prognostic factor in ovarian cancer and that targeting c-Met in vivo inhibits peritoneal dissemination and invasion through an α5β1 integrin-dependent mechanism. Therefore, c-Met should be explored further as a therapeutic target in ovarian cancer. [Cancer Res 2007;67(4):1670–9]