bluuebunny/crossref_metadata_2025 huggingface dataset:
ULTRASONOGRAPHIC EVALUATION OF UNION IN LONG BONES FRACTURES
Authors: Dudkiewicz Israel , Heim Michael , Salai Moshe , Blankstein Alexander
Published: July 2009

Introduction: To follow fracture healing, radiography is commonly used, but it is not sensitive to the early stages of this healing process when nonossified callus is formed. Hence, radiography can lag behind the physiological events of bone healing by some weeks. Although the use of ultrasound for fracture diagnosis has been reported previously, mainly in children, the clinical use of ultrasound to follow fracture healing has rarely been commented on. The goal of the current study was to test the efficiency and efficacy of ultrasound as an alternative method for follow-up of fracture healing. Material and Methods: During a one-year period, 12 patients—six with proximal fibula fracture and six with proximal metatarsal fractures—were followed by ultrasonographic examination in parallel with the routine radiographs. Results: The ultrasound examinations revealed callus formation after one month, with the early signs of healing after ten days. Early callus was first seen on radiographs after a month. Conclusion: Ultrasound was found to be a good modality to follow up fracture healing in long bones. This modality can reduce the amount of radiation received by the patients in the follow-up of fractures, and may shorten the immobility period and hence the recovery time of returning to normal function.
VITAMIN SUPPLEMENTS AND RADIOGRAPHIC KNEE OSTEOARTHRITIS: THE CLEARWATER OSTEOARTHRITIS STUDY
Authors: Wilder Frances Vaughn , Leaverton Paul E. , Rogers Matthew W. , Lemrow Nancy B.
Published: July 2009

Objective: To evaluate the association between vitamin supplements and the incidence and progression of radiographic knee osteoarthritis (OA). Study Design: Prospective cohort. Methods: Men and women aged 40 years and older (N = 2239) participating in the community-based Clearwater Osteoarthritis Study (1988–current) with biennial, sequential radiographs. The Lawrence & Kellgren ordinal scale was used to determine evidence of the study outcome, radiographic knee OA, and progression of radiographic knee OA. The study exposure was baseline history of self-reported vitamin supplement usage. Results: Individuals without baseline knee OA who self-reported vitamin supplement usage were 12% less likely to develop knee OA than were those individuals who self-reported no vitamin supplement usage (RR = 0.88; 95% C.I. 0.86–0.89). Those with baseline knee OA who self-reported vitamin supplement usage were 7% less likely to experience knee OA progression than were those individuals who self-reported no vitamin supplement usage (RR = 0.93; 95% C.I. 0.87–0.99). Conclusion: After consideration of BMI, gender, age, history of knee trauma, exercise and vitamin supplement usage prior to study baseline, these findings suggest that vitamin supplement usage may play a protective role in knee OA. Vitamin supplements may be a cost-effective strategy to reduce the incidence and/or slow the progression of knee OA. As many approved OA drugs are accompanied by adverse side effects, the role of vitamin supplements in the development and progression of knee OA warrants further investigation.
ON A FINITE HORIZON STARTING AND STOPPING PROBLEM WITH RISK OF ABANDONMENT
Authors: DJEHICHE BOUALEM , HAMADÈNE SAID
Published: July 2009

We address the issue of finding a strategy to sustain structural profitability of an investment project, whose production activity depends on the market price of a number of underlying commodities. Depending on the fluctuating prices of these commodities, the activity will either continue until the project's profitability reaches a critical low level at which it is stopped and starts again when it becomes profitable. But, if the structural nonprofitability remains for a while, the investment project will face the risk to be abandoned or be definitely closed. We suggest a general probabilistic set up to model profitability as a function of the market price of a set of commodities, and find the related optimal strategy to sustain it, under the constraint that the project faces the abandonment risk when being nonprofitable under a fixed finite time interval. When the market price dynamics is described by a diffusion process, we show that the optimal strategy is related to viscosity solutions of a system of two variational inequalities with inter-connected obstacles.
ON THE RELATIONSHIP BETWEEN THE CALL PRICE SURFACE AND THE IMPLIED VOLATILITY SURFACE CLOSE TO EXPIRY
Authors: ROPER MICHAEL , RUTKOWSKI MAREK
Published: July 2009

We examine the asymptotic behaviour of the call price surface and the associated Black-Scholes implied volatility surface in the small time to expiry limit under the condition of no arbitrage. In the final section, we examine a related question of existence of a market model with non-convergent implied volatility. We show that there exist arbitrage free markets in which implied volatility may fail to converge to any value, finite or infinite.
A VIKOR-BASED MULTIPLE CRITERIA DECISION METHOD FOR IMPROVING INFORMATION SECURITY RISK
Authors: OU YANG YU-PING , SHIEH HOW-MING , LEU JUN-DER , TZENG GWO-HSHIUNG
Published: July 2009

Most multicriteria methods focus on ranking and selecting from a set of alternatives. These methods are usually used to compare all alternatives based on the synthesized scorings within a normalized scale with respect to the same criteria in multicriteria problems. However, the decision makers often simultaneously manage one or several alternatives/projects with conflicting and noncommensurable criteria to reduce the gaps to achieve the aspired grade in practice. They then need to rank the gaps that have not been reduced or improved (the unimproved gaps) for the alternatives/projects or aspects of a project to get the most benefit. Because these compared alternatives/projects do not usually have the same criteria/aspects, traditional methods are unsuitable to deal with them. Thus, this research proposes a new VIKOR method to solve this problem; this new method allows the decision maker to understand these gaps of the projects/aspects and rank them to improve these large gaps in control items to achieve the aspired level. Its concept originates in compromise solutions, in particular the VIKOR method. In addition, this research also provides an example of improving information security risk to demonstrate the suitability of this new method. The results show the effectiveness of the new method.
DISTRIBUTION OF MULTI-WORDS IN CHINESE AND ENGLISH DOCUMENTS
Authors: ZHANG WEN , YOSHIDA TAKETOSHI , TANG XIJIN
Published: July 2009

As a hybrid of N-gram in natural language processing and collocation in statistical linguistics, multi-word is becoming a hot topic in area of text mining and information retrieval. In this paper, a study concerning distribution of multi-words is carried out to explore a theoretical basis for probabilistic term-weighting scheme. Specifically, the Poisson distribution, zero-inflated binomial distribution, and G-distribution are comparatively studied on a task of predicting probabilities of multi-words' occurrences using these distributions, for both technical multi-words and nontechnical multi-words. In addition, a rule-based multi-word extraction algorithm is proposed to extract multi-words from texts based on words' occurring patterns and syntactical structures. Our experimental results demonstrate that G-distribution has the best capability to predict probabilities of frequency of multi-words' occurrence and the Poisson distribution is comparable to zero-inflated binomial distribution in estimation of multi-word distribution. The outcome of this study validates that burstiness is a universal phenomenon in linguistic count data, which is applicable not only for individual content words but also for multi-words.
RELATIVE RATIO METHOD FOR MULTIPLE ATTRIBUTE DECISION MAKING PROBLEMS
Authors: LI DENG-FENG
Published: July 2009

The multiple attribute decision making (MADM) is an important research field in decision science and operations research. Recently, several commonly used methods such as the TOPSIS and the VIKOR were proposed to solve the MADM problems. The TOPSIS and VIKOR are based on aggregating functions representing closeness to the ideal, which originated in the compromise programming method. The aim of this paper is to develop a new methodology called the relative ratio (RR) for the MADM problems. In this RR method, a compromise solution/alternative is determined based on the concept that the chosen alternative should be as close to the ideal solution as possible and as far away from the negative-ideal solution as possible simultaneously. The computation principle and procedure of the RR method are described in detail in this paper. Moreover comparisons of the RR method with the TOPSIS as well as the VIKOR are made theoretically and illustrated with a numerical example.
INDIVIDUAL AND SOCIAL STRATEGIES TO DEAL WITH IGNORANCE SITUATIONS IN MULTI-PERSON DECISION MAKING
Authors: ALONSO S. , HERRERA-VIEDMA E. , CHICLANA F. , HERRERA F.
Published: July 2009

Multi-person decision making problems involve the preferences of some experts about a set of alternatives in order to find the best one. However, sometimes experts might not possess a precise or sufficient level of knowledge of part of the problem and as a consequence that expert might not give all the information that is required. Indeed, this may be the case when the number of alternatives is high and experts are using fuzzy preference relations to represent their preferences. In the literature, incomplete information situations have been studied, and as a result, procedures that are able to compute the missing information of a preference relation have been designed. However, these approaches usually need at least a piece of information about every alternative in the problem in order to be successful in estimating all the missing preference values.

In this paper, we address situations in which an expert does not provide any information about a particular alternative, which we call situations of total ignorance. We analyze several strategies to deal with these situations. We classify these strategies into: (i) individual strategies that can be applied to each individual preference relation without taking into account any information from the rest of experts and (ii) social strategies, that is, strategies that make use of the information available from the group of experts. Both individual and social strategies use extra assumptions or knowledge, which could not be directly instantiated in the experts preference relations. We also provide an analysis of the advantages and disadvantages of each one of the strategies presented, and the situations where some of them may be more adequate to be applied than the others.
DYADIC THEORETICAL GAMES MODELS OF DECISION-MAKING FOR THE LEXICOGRAPHIC VECTOR PAYOFFS
Authors: SALUKVADZE MINDIA E. , BELTADZE GURAM , CRIADO FRANCISCO
Published: July 2009

This article is about the full analysis of one concrete class of general non-cooperative lexicographic games and its computer programming. In such game, the payoffs of players are lexicographic vector payoffs — m scalar criteria vectors. At the same time, these criteria are strictly ranked on the set of the situations with lexicographic preference. In some such kind of game a Nash's equilibrium may not exist. In the given article the full analysis of one class of dyadic lexicographic games is worked out. Such kind of class is the non-cooperative lexicographic games, where each player has got two pure strategies and the payoff of each player solely depends on the strategies of two players in each situation. Therefore, the player's payoffs are given by 2 × 2 matrices, the elements of which are lexicographic utilities.
A NOVEL CPG WITH PROPRIOCEPTION AND ITS APPLICATION ON THE LOCOMOTION CONTROL OF QUADRUPED ROBOT
Authors: SUN LEI , MENG MAX Q.-H. , LI SHUAI , LIANG HUAWEI , MEI TAO
Published: July 2009

This paper proposes a novel central pattern generator (CPG) model with proprioceptive mechanism and the dynamic connectivity mechanism. It not only contains the sensory information of the environment but also contains the information of the actuators and automatically tunes the parameters of CPG corresponding to the actuators information and inner sensory information. The position of the joints linked directly with the output of CPG is introduced to the CPG to find its proprioceptive system, spontaneously making the robot realize the actuator working status, further changing the CPG output to fit the change and decrease the influence of the problematic joints or actuators on the robot being controlled. So the damage would be avoided and self-protection is implemented. Its application on the locomotion control of a quadruped robot demonstrates the effectiveness of the proposed approach.
REAL-TIME OBJECT DETECTION USING TWO BACKGROUND MODELS UNDER SHAKING CAMERA
Authors: KIM TAEHO , JO KANG-HYUN
Published: July 2009

In this paper, we propose a novel approach to detect moving objects by two background models, multiple background model (MBM) and temporal median background (TMB), from hand-taken image sequence. For this purpose, we record image sequences by hand-held camera without tripod so every frame has variation between consecutive frames. A pixel-based background model is fragile while image sequence has variation. Therefore we calculate the camera movement using correlation between two consecutive images and it helps us to generate MBM under shaking camera. The computational cost of correlation quickly increases if image resolution increases. Hence, we use edge segments to reduce computational cost. These edge segments are gathered by Sobel operator and those are distinctive spatial features to calculate similarity between two regions, belonging to current and previous images, organized by neighbors of edge segments. Based on the similarity result, we obtain a set of best matched regions, centroids of matched regions, and displacement vectors from each pair of previous and current images. Each displacement vector in a set describes the transition of each matched region in the image pair. Using the highest density of displacement vector histogram, we choose the camera motion vector, indicates camera movement between consecutive frames. According to the camera motion vector, every pixel in a current image is related to different position pixels in a previous image. The pixel relation is used to generate MBM in this paper, unlike original MBM [Xiao, M., Han, C. and Kang, K. [2006]. Proc. Int. Conf. Information Fuscon, pp. 1–7.]. The MBM algorithm classifies the variation of pixel values in frame sequence to several clusters. Classification of varying pixel values to several clusters is similar with mixture of gaussian (MOG). Nevertheless, MBM has low cost to calculate because it does not need to estimate parameter. However, MBM is not sensitive to short period changes. Therefore, we use TMB to support MBM. The experimental result shows that proposed algorithm successfully detects moving objects using background subtraction less than 25 ms per frame when camera has 2D translation.
TOWARD A DYNAMIC PERSPECTIVE ON OPEN INNOVATION: A LONGITUDINAL ASSESSMENT OF THE ADOPTION OF INTERNAL AND EXTERNAL INNOVATION STRATEGIES IN THE NETHERLANDS
Authors: POOT TOM , FAEMS DRIES , VANHAVERBEKE WIM
Published: July 2009

The purpose of this paper is to contribute to a more dynamic perspective on open innovation by conducting a longitudinal analysis of the adoption of open innovation strategies. In order to do so, we rely on three comparable waves of the Dutch Community Innovation Survey, which were conducted in 1996, 2000 and 2004. The contributions of this study are twofold. First, this study is to our knowledge the first one to explicitly provide large-scale evidence of a paradigm shift from a closed to an open innovation model is taking place. At the same time, we provide evidence that this paradigm shift tends to occur in shocks instead of manifesting itself as a continuous process over time. Moreover, we show that the timing of these shocks differs across industries. Second, this study supports the assumption that internal and external innovation strategies are complements instead of substitutes.
PRACTICES OF STRATEGIC FORESIGHT IN BIOTECH COMPANIES
Authors: MIETZNER DANA , REGER GUIDO
Published: July 2009

This paper deals with the practice and requirements of strategic foresight in biotechnology firms. Processes and the degree of method application of strategic foresight are less investigated in small- and medium-sized enterprises. Based on case study research of 30 biotechnology companies in Germany, six different approaches of strategic foresight are identified. The study shows how strategic foresight is organised, which methods for strategic foresight are implemented, who is responsible for strategic foresight, what the main characteristics of the different approaches are, and how the strengths and weaknesses of strategic foresight practice in biotechnology firms can be characterized. Furthermore, firms' requirements for suitable foresight processes and methods are identified within the scope of case study research.
INNOVATIVENESS AND INTERNATIONAL OPERATIONS: CASE OF RUSSIAN R&D COMPANIES
Authors: PODMETINA DARIA , SMIRNOVA MARIA , VÄÄTÄNEN JUHA , TORKKELI MARKO
Published: July 2009

The number of Russian companies entering international markets has increased dramatically in the last 10 years. The development of innovative industries has intensified as well. Do innovations play significant role in internationalisation? Do innovators internationalize more actively? Does operating on international markets make companies more innovative? This paper studies innovations and internationalisation of companies in Russia, based on the survey of R&D-oriented companies located in the two most developed areas of Russia (St. Petersburg and Moscow). The study aims to identify the clusters of companies according to their exports and R&D expenditures, and fulfil in-depth analysis of innovations-related determinants that could explain the structure of the clusters. The main results of the study show the significant impact of innovation activities, competition and new product development on export intensity.
APPROXIMATING THE JOINT REPLENISHMENT PROBLEM WITH DEADLINES
Authors: NONNER TIM , SOUZA ALEXANDER
Published: July 2009

The objective of the classical Joint Replenishment Problem (JRP) is to minimize ordering costs by combining orders in two stages, first at some retailers, and then at a warehouse. These orders are needed to satisfy demands that appear over time at the retailers. We investigate the natural special case that each demand has a deadline until when it needs to be satisfied. For this case, we present a randomized 5/3-approximation algorithm. We moreover prove that JRP with deadlines is APX-hard. Finally, we extend the known hardness results by showing that JRP with linear delay cost functions is NP-hard, even if each retailer has to satisfy only three demands.
A BETTER APPROXIMATION FOR MINIMUM AVERAGE ROUTING PATH CLUSTERING PROBLEM IN 2-D UNDERWATER SENSOR NETWORKS
Authors: WANG WEI , KIM DONGHYUN , WILLSON JAMES , THURAISINGHAM BHAVANI , WU WEILI
Published: July 2009

Previously, we proposed Minimum Average Routing Path Clustering Problem (MARPCP) in multi-hop USNs. The goal of this problem is to find a clustering of a USN so that the average clustering-based routing path from a node to it nearest underwater sink is minimized. We relaxed MARPCP to a special case of Minimum Weight Dominating Set Problem (MWDSP), namely MWDSP-R. In addition, we showed the Performance Ratio (PR) of α-approximation algorithm for MWDSP-R is 3α for MARPCP. Based on this result, we showed the existence of a (15 + ∊)-approximation algorithm for MARPCP. In this paper, we first establish the NP-completeness of both MARPCP and MWDSP-R. Then, we propose a PTAS for MWDSP-R. By combining this result with our previous one, we have a (3 + ∊)-approximation algorithm for MARPCP.
MINIMUM ENERGY BROADCAST ROUTING IN AD HOC AND SENSOR NETWORKS WITH DIRECTIONAL ANTENNAS
Authors: LI ZHENG , LI DEYING
Published: July 2009

In this paper we discuss minimum energy broadcast routing with directional antennas in ad hoc and sensor networks. We assume that the network consists of sensor nodes whose antennas are switched beam directional antennas. The problem of our concern is: a given set V with n nodes and each node vi has l(i) transmission directions (i.e. the antenna sectors) and a broadcast request sourced at s, how to find a broadcast tree rooted at s and spanning all nodes in V such that the total energy is minimized. This problem involves with the choice of transmitting nodes and their transmission directions, which is NP-hard. We firstly propose a directed Steiner tree-based approximation algorithm for this problem and discuss its distributed implementation. Then we also propose a |V|-approximation algorithm and one heuristic with lower time complexities. Extensive simulations have demonstrated the efficiency of our algorithms.
BICRITERIA SCHEDULING ON SINGLE-MACHINE WITH INVENTORY OPERATIONS
Authors: FAN BAOQIANG , CHEN RONGJUN , TANG GUOCHUN
Published: July 2009

In this paper, we consider the single machine scheduling problem with inventory operations. The objective is to minimize makespan subject to the constraint that the total number of tardy jobs is minimum. We show the problem is strongly NP-hard. A polynomial [Formula: see text]-approximation scheme for the problem is presented, where m is defined as the total job's processing times ∑ pj divided by the capacity c of the storage, and an optimal algorithm for a special case of the problem, in which each job is one unit in size.
EFFICIENT ROUTING ALGORITHMS FOR GENERALIZED SHUFFLE-EXCHANGE NETWORKS
Authors: LAN JAMES K. , CHOU WELL Y. , CHEN CHIUYUAN
Published: July 2009

The shuffle-exchange network has been proposed as a popular architecture for multistage interconnection networks. In 1991, Padmanabhan introduced the generalized shuffle-exchange network (GSEN) and proposed an efficient routing algorithm. Later, Chen et al. further enhanced the GSEN with bidirectional links and proposed the bidirectional GSEN (BGSEN). A BGSEN consists of the forward and the backward network. Based on the idea of inversely using the control tag generated by Padmanabhan's algorithm, Chen et al. proposed a routing algorithm for the backward network. Recently, Chen and Lou also proposed a routing algorithm for the backward network. It should be noted, however, that Padmanabhan's algorithm is actually an explicit formula for computing the control tag for routing and takes only O(1) time. Neither the algorithm of Chen et al. nor the algorithm of Chen and Lou provides an explicit formula for computing the control tag for routing and both algorithms take at least Ω(n) time, where n + 1 is the number of stages in the BGSEN. This paper attempts to propose an explicit formula for computing the control tag for routing in the backward network. We will demonstrate how this formula greatly simplifies the computation process and how it leads to efficient routing algorithms. In particular, an O(1)-time one-to-one routing algorithm and an efficient routing-table construction algorithm have been proposed.
A PTAS FOR MINIMUM d-HOP UNDERWATER SINK PLACEMENT PROBLEM IN 2-D UNDERWATER SENSOR NETWORKS
Authors: WANG WEI , KIM DONGHYUN , SOHAEE NASSIM , MA CHANGCUN , WU WEILI
Published: July 2009

The multiple UnderWater Sink (UW-Sink) architecture is introduced to resolve the scalability problem in USNs. To maximize the benefit of this architecture, the UW-Sinks should be located carefully. Previously, we proposed Minimum d-Hop UW-Sink Placement Problem (MdHUWSPP) for time-sensitive applications, whose objective is minimizing the number of UW-Sinks which d-hop dominate a given USN. In this paper, we present a PTAS for MdHUWSPP. We introduce an algorithm to partition an input graph representing the USN, find local optimum solutions, and return the union of the local solutions. Later, we use this algorithm with the shifting technique to have a PTAS for MdHUWSPP.
ON (3, 1)*-CHOOSABILITY OF TOROIDAL GRAPHS
Authors: DONG WEI , XU BAOGANG
Published: July 2009

A list-assignment L to the vertices of G is an assignment of a set L(v) of colors to vertex v for every v ∈ V(G). Given a list-assignment L and integer d ≥ 0, an (L, d)*-coloring of a graph G is a mapping ϕ that assigns a color ϕ(v) ∈ L(v) to each vertex v ∈ V(G) such that at most d neighbors of v receive color ϕ(v). A graph is called (k,d)*-choosable, if G admits an (L, d)*-coloring for every list assignment L with |L(v)| ≥ k for all v ∈ V(G). In this note, it is proved that every toroidal graph, which contains neither i-cycles nor j-cycles for any subset {i, j} ⊆ {3, 4, 6}, is (3, 1)*-choosable.
Mechanisms of Lipid Transport Involved in Organelle Biogenesis in Plant Cells
Authors: Benning Christoph
Published: July 2009

Chloroplasts are the defining organelle of photoautotrophic plant cells. Photosynthetic light reactions and electron transport are the functions of an elaborate thylakoid membrane system inside chloroplasts. The lipid composition of photosynthetic membranes is characterized by a substantial fraction of nonphosphorous galactoglycerolipids reflecting the need of sessile plants to conserve phosphorus. Lipid transport and assembly of glycerolipids play an essential role in the biogenesis of the photosynthetic apparatus in developing chloroplasts. During chloroplast biogenesis, fatty acids are synthesized in the plastid and are exported to the endoplasmic reticulum, where they are incorporated into membrane lipids. Alternatively, lipids can also be assembled de novo at the inner envelope membrane of plastids in many plants. A rich repertoire of lipid exchange mechanisms involving the thylakoid membranes, the chloroplast inner and outer envelope membranes, and the endoplasmic reticulum is emerging. Studies of thylakoid biogenesis provide new insights into the general mechanisms of intermembrane lipid transfer.
The Intersection of Work and Family Life: The Role of Affect
Authors: Eby Lillian T. , Maher Charleen P. , Butts Marcus M.
Published: July 2009

This review examines the role that trait-based and state-based affect plays in understanding the intersection of work and family life. We start with the definition of key terms and concepts. This is followed by a historical overview of the two bodies of scholarship that are the focus of this review, the work-family interface and affect. Next, we provide a review and synthesis of 79 empirical studies examining affect in relation to work-family interaction, organized around three perspectives: the dispositional perspective, the state-based specific affective reactions perspective, and the state-based global affective reactions perspective. A methodological critique of these studies follows, providing a springboard for the discussion of recommended methodologies and data analytic approaches, along with directions for future research.
17β-Estradiol restores excitability of a sexually dimorphic subset of myelinated vagal afferents in ovariectomized rats
Authors: Qiao Guo-Fen , Li Bai-Yan , Lu Yan-Jie , Fu Yi-Li , Schild John H.
Published: July 2009

We recently identified a myelinated vagal afferent subpopulation (Ah type) far more prevalent in female than male rats and showed that this difference extends to functionally specific visceral sensory afferents, baroreceptors of the aortic arch. Excitability of myelinated Ah-type afferents is markedly reduced after ovariectomy (OVX). Here we tested the hypothesis that 17β-estradiol can selectively restore excitability of these sex-specific vagal afferents. Acutely isolated vagal afferent neurons (VGN) from intact and OVX adult female rats were used with patch-clamp technique and current-clamp protocols to assess the effect of acute application of 17β-estradiol on neuronal excitability. At over physiologically relevant 17β-estradiol concentrations for rat (1–10 nM) excitability of myelinated Ah-type vagal afferents is restored to discharge frequencies comparable to those in intact females, albeit with some interesting differences related to burst and sustained patterns of neuronal discharge. Restoration of excitability occurs within 3 min of hormone application and is stereo specific, because 1,000 nM 17α-estradiol fails to alter excitability. Furthermore, activation of G protein-coupled estrogen receptor GPR30 with highly selective agonist G-1 similarly restores excitability of Ah-type afferents. The effectiveness of 17β-estradiol and G-1 is completely eliminated by application of high-affinity estrogen receptor ligand ICI-182,780. 17β-Estradiol conjugated with BSA is ∼70% as effective as 17β-estradiol alone in restoring Ah-type VGN excitability. These data support our conclusions that the cellular mechanisms leading to rapid restoration of neuronal excitability of myelinated Ah-type VGN after OVX occur, at least in part, via membrane-bound estrogen receptors. We contend that recovery of high-frequency discharge at physiologically relevant 17β-estradiol concentrations implies that this unique subtype of low-threshold myelinated vagal afferent may account for some of the sex-related differences in visceral organ system function. Sex differences in cardiovascular and gastrointestinal function and the potential role of GPR30 in modulation of sex-specific myelinated Ah-type vagal afferents are discussed.
Extracellular potassium dependence of the Na+-K+-ATPase in cardiac myocytes: isoform specificity and effect of phospholemman
Authors: Han Fei , Tucker Amy L. , Lingrel Jerry B. , Despa Sanda , Bers Donald M.
Published: July 2009

Cardiac Na+-K+-ATPase (NKA) regulates intracellular Na+, which in turn affects intracellular Ca2+ and contractility via the Na+/Ca2+ exchanger. Extracellular K+ concentration ([K+]) is a central regulator of NKA activity. Phospholemman (PLM) has recently been recognized as a critical regulator of NKA in the heart. PLM reduces the intracellular Na+ affinity of NKA, an effect relieved by PLM phosphorylation. Here we tested whether the NKA α1- vs. α2- isoforms have different external K+ sensitivity and whether PLM and PKA activation affects the NKA affinity for K+ in mouse cardiac myocytes. We measured the external [K+] dependence of the pump current generated by the ouabain-resistant NKA isoform in myocytes from wild-type (WT) mice (i.e., current due to NKA-α1) and mice in which the NKA isoforms have swapped ouabain affinities (α1 is ouabain sensitive and α2 is ouabain resistant) to assess current due to NKA-α2. We found that NKA-α1 has a higher affinity for external K+ than NKA-α2 [half-maximal pump activation ( K0.5) = 1.5 ± 0.1 vs. 2.9 ± 0.3 mM]. The apparent external K+ affinity of NKA was significantly lower in myocytes from WT vs. PLM-knockout mice ( K0.5 = 2.0 ± 0.2 vs. 1.05 ± 0.08 mM). However, PKA activation by isoproterenol (1 μM) did not alter the K0.5 of NKA for external K+ in WT myocytes. We conclude that 1) NKA-α1 has higher affinity for K+ than NKA-α2 in cardiac myocytes, 2) PLM decreases the apparent external K+ affinity of NKA, and 3) phosphorylation of PLM at the cytosolic domain does not alter apparent extracellular K+ affinity of NKA.
AMP-activated protein kinase and nitric oxide regulate the glucose sensitivity of ventromedial hypothalamic glucose-inhibited neurons
Authors: Murphy Beth Ann , Fakira Kurt A. , Song Zhentao , Beuve Annie , Routh Vanessa H.
Published: July 2009

The mechanisms by which glucose regulates the activity of glucose-inhibited (GI) neurons in the ventromedial hypothalamus (VMH) are largely unknown. We have previously shown that AMP-activated protein kinase (AMPK) increases nitric oxide (NO) production in VMH GI neurons. We hypothesized that AMPK-mediated NO signaling is required for depolarization of VMH GI neurons in response to decreased glucose. In support of our hypothesis, inhibition of neuronal nitric oxide synthase (nNOS) or the NO receptor soluble guanylyl cyclase (sGC) blocked depolarization of GI neurons to decreased glucose from 2.5 to 0.7 mM or to AMPK activation. Conversely, activation of sGC or the cell-permeable analog of cGMP, 8-bromoguanosine 3′,5′-cyclic monophosphate (8-Br-cGMP), enhanced the response of GI neurons to decreased glucose, suggesting that stimulation of NO-sGC-cGMP signaling by AMPK is required for glucose sensing in GI neurons. Interestingly, the AMPK inhibitor compound C completely blocked the effect of sGC activation or 8-Br-cGMP, and 8-Br-cGMP increased VMH AMPKα2 phosphorylation. These data suggest that NO, in turn, amplifies AMPK activation in GI neurons. Finally, inhibition of the cystic fibrosis transmembrane regulator (CFTR) Cl− conductance blocked depolarization of GI neurons to decreased glucose or AMPK activation, whereas decreased glucose, AMPK activation, and 8-Br-cGMP increased VMH CFTR phosphorylation. We conclude that decreased glucose triggers the following sequence of events leading to depolarization in VMH GI neurons: AMPK activation, nNOS phosphorylation, NO production, and stimulation of sGC-cGMP signaling, which amplifies AMPK activation and leads to closure of the CFTR.
Membrane depolarization induces calcium-dependent upregulation of Hsp70 and Hmox-1 in skeletal muscle cells
Authors: Jorquera Gonzalo , Juretić Nevenka , Jaimovich Enrique , Riveros Nora
Published: July 2009

Heat shock proteins (HSPs) are a conserved family of cytoprotective polypeptides, synthesized by cells in response to stress. Hsp70 and heme oxygenase 1 (Hmox-1) are induced by a variety of cellular stressors in skeletal muscle, playing a role in long-term adaptations and muscle fibers regeneration. Though HSPs expression after exercise has been intensely investigated, the molecular mechanisms concerning Hsp70 and Hmox-1 induction are poorly understood. The aim of this work was to investigate the involvement of calcium in Hsp70 and Hmox-1 expression upon depolarization of skeletal muscle cells. We observed that depolarization of myotubes increased both mRNA levels and protein expression for Hsp70 and Hmox-1. Stimulation in the presence of intracellular calcium chelator BAPTA-AM resulted in a complete inhibition of Hsp70-induced expression. It is known that inositol-1,4,5-trisphophate (IP3)-mediated slow Ca2+transients, evoked by membrane depolarization, are involved in the regulation of gene expression. Here we demonstrated that inhibition of IP3-dependent calcium signals decreased both Hsp70 mRNA induction and Hsp70 and Hmox-1 protein expression. Inhibitors of calcium-dependent protein kinase C also abolished Hsp70 mRNA induction. Our results provide evidence that membrane depolarization increases Hsp70 and Hmox-1 expression in cultured skeletal muscle cells, which the effect is critically dependent on Ca2+released from IP3-sensitive intracellular stores and that it involves PKC as an upstream effector in Hsp70 mRNA-induced expression.
MaxiK potassium channels in the function of chemoreceptor cells of the rat carotid body
Authors: Gomez-Niño Angela , Obeso Ana , Baranda Jose Antonio , Santo-Domingo Jaime , Lopez-Lopez Jose Ramon , Gonzalez Constancio
Published: July 2009

Hypoxia activates chemoreceptor cells of the carotid body (CB) promoting an increase in their normoxic release of neurotransmitters. Catecholamine (CA) release rate parallels the intensity of hypoxia. Coupling of hypoxia to CA release requires cell depolarization, produced by inhibition of O2-regulated K+channels, and Ca2+entering the cells via voltage-operated channels. In rat chemoreceptor cells hypoxia inhibits large-conductance, calcium-sensitive K channels (maxiK) and a two-pore domain weakly inward rectifying K+channel (TWIK)-like acid-sensitive K+channel (TASK)-like channel, but the significance of maxiK is controversial. A proposal envisions maxiK contributing to set the membrane potential ( Em) and the hypoxic response, but the proposal is denied by authors finding that maxiK inhibition does not depolarize chemoreceptor cells or alters intracellular Ca2+concentration or CA release in normoxia or hypoxia. We found that maxiK channel blockers (tetraethylammonium and iberiotoxin) did not modify CA release in rat chemoreceptor cells, in either normoxia or hypoxia, and iberiotoxin did not alter the Ca2+transients elicited by hypoxia. On the contrary, both maxiK blockers increased the responses elicited by dinitrophenol, a stimulus we demonstrate does not affect maxiK channels in isolated patches of rat chemoreceptor cells. We conclude that in rat chemoreceptor cells maxiK channels do not contribute to the genesis of the Em, and that their full inhibition by hypoxia, preclude further inhibition by maxiK channel blockers. We suggest that full inhibition of this channel is required to generate the spiking behavior of the cells in acute hypoxia.
Glycine and urea kinetics in nonalcoholic steatohepatitis in human: effect of intralipid infusion
Authors: Dasarathy Srinivasan , Kasumov Takhar , Edmison John M. , Gruca Lourdes L. , Bennett Carole , Duenas Clarita , Marczewski Susan , McCullough Arthur J. , Hanson Richard W. , Kalhan Satish C.
Published: July 2009

The rates of oxidation of glycine and ureagenesis were quantified in the basal state and in response to an intravenous infusion of intralipid with heparin (IL) in healthy subjects ( n = 8) and in subjects with nonalcoholic steatohepatitis (NASH) ( n = 6). During fasting, no significant difference in weight-specific rate of appearance ( Ra) of glycine, glycine oxidation, and urea synthesis was observed. Intralipid infusion resulted in a significant increase in plasma β-hydroxybutyrate in both groups. The correlation between free fatty acids and β-hydroxybutyrate concentration in plasma was 0.94 in NASH compared with 0.4 in controls, indicating greater hepatic fatty acid oxidation in NASH. Intralipid infusion resulted in a significant decrease in urea synthesis and glycine Rain both groups and did not impact glycine oxidation. The fractional contribution of glycine carbon to serine was lower in subjects with NASH before and after IL infusion. In contrast, the fractional contribution of serine carbon to cystathionine was higher in NASH before and following IL infusion. These results suggest that hepatic fatty acid oxidation is higher in NASH compared with controls and that glycine oxidation and urea synthesis are not altered. An increase in oxidative stress, induced by a higher rate of fatty acid oxidation in NASH, may have caused an increase in the contribution of serine to cystathionine to meet the higher demands for glutathione.
Modulation of ileal apical Na+-dependent bile acid transporter ASBT by protein kinase C
Authors: Sarwar Zaheer , Annaba Fadi , Dwivedi Alka , Saksena Seema , Gill Ravinder K. , Alrefai Waddah A.
Published: July 2009

Ileal apical Na+-dependent bile acid transporter (ASBT) is responsible for reabsorbing the majority of bile acids from the intestinal lumen. Rapid adaptation of ASBT function in response to physiological and pathophysiological stimuli is essential for the maintenance of bile acid homeostasis. However, not much is known about molecular mechanisms responsible for acute posttranscriptional regulation of ileal ASBT. The protein kinase C (PKC)-dependent pathway represents a major cell signaling mechanism influencing intestinal epithelial functions. The present studies were, therefore, undertaken to investigate ASBT regulation in intestinal Caco-2 monolayers by the well-known PKC activator phorbol 12-myristate 13-acetate (PMA). Our results showed that Na+-dependent [3H]taurocholic acid uptake in Caco-2 cells was significantly inhibited in response to 2 h incubation with 100 nM PMA compared with incubation with 4α-PMA (inactive form). The inhibitory effect of PMA was blocked in the presence of 5 μM bisindolylmaleimide I (PKC inhibitor) but not 1,2-bis(2-aminophenoxy)ethane- N,N,N′,N′-tetraacetic acid-AM (Ca2+chelator) or LY-294002 (phosphatidylinositol 3-kinase inhibitor). PMA inhibition of ASBT function was also abrogated in the presence of myristoylated PKCζ pseudosubstrate peptide, indicating involvement of the atypical PKCζ isoform. The inhibition by PMA was associated with a significant decrease in the maximal velocity of the transporter and a reduction in ASBT plasma membrane content, suggesting a modulation by vesicular recycling. Our novel findings demonstrate a posttranscriptional modulation of ileal ASBT function and membrane expression by phorbol ester via a PKCζ-dependent pathway.
An imbalance of esophageal effector and regulatory T cell subsets in experimental eosinophilic esophagitis in mice
Authors: Zhu Xiang , Wang Meiqin , Crump Caleb H. , Mishra Anil
Published: July 2009

We recently reported a critical role for T cells in the induction of eosinophilic esophagitis (EE) in mice; however, the role of specific T cell subsets in disease pathogenesis is not yet understood. In the current study, we tested the hypothesis that allergen-induced EE develops in response to the disproportion of functionally different effector and regulatory T cells in the esophagus. Fluorescence-activated cell sorter analysis was performed to examine activated T cell subsets using the cell surface activation markers CD25 and CD69. A significant increase in activated CD4+ and CD4− T cells was observed in the total esophageal cells isolated from the mouse model of EE. Furthermore, an imbalance in the effector and regulatory T cells was observed in the esophagus. The esophageal CD4+CD45RBhigh effector T cells in allergen-challenged mice increased compared with saline-challenged mice (65.4 ± 3.6 × 103 to 44.8 ± 4.2 × 103), whereas CD4+CD45RBlow mostly regulatory T cells decreased in allergen-challenged mice compared with saline-challenged mice (5.8 ± 0.9 × 103 from 10.2 ± 1.7 × 103). The functional characteristics were examined by analysis of the pro- and anti-inflammatory cytokine profile of purified low and high CD4+CD45RB subsets from the spleen. Additionally, a significantly reduced interleukin (IL)-2 production by CD4+CD45RBlow cells in allergen-challenged mice compared with saline-challenged mice was observed. The reduced IL-2 in the CD4+CD45RBlow subset may be associated with reduction of CD4+CD45RBlow subset. In conclusion, our results suggest that local regulatory interaction of CD45RBhigh and CD45RBlow CD4+ T cells may be required for protective and pathogenic immunity in EE.
Neuropeptide Y and neurovascular control in skeletal muscle and skin
Authors: Hodges Gary J. , Jackson Dwayne N. , Mattar Louis , Johnson John M. , Shoemaker J. Kevin
Published: July 2009

Neuropeptide Y (NPY) is a ubiquitous peptide with multiple effects on energy metabolism, reproduction, neurogenesis, and emotion. In addition, NPY is an important sympathetic neurotransmitter involved in neurovascular regulation. Although early studies suggested that the vasoactive effects of NPY were limited to periods of high stress, there is growing evidence for the involvement of NPY on baseline vasomotor tone and sympathetically evoked vasoconstriction in vivo in both skeletal muscle and the cutaneous circulation. In Sprague-Dawley rat skeletal muscle, Y1-receptor activation appears to play an important role in the regulation of basal vascular conductance, and this effect is similar in magnitude to the α1-receptor contribution. Furthermore, under baseline conditions, agonist and receptor-based mechanisms for Y1-receptor-dependent control of vascular conductance in skeletal muscle are greater in male than female rats. In skin, there is Y1-receptor-mediated vasoconstriction during whole body, but not local, cooling. As with the NPY system in muscle, this neural effect in skin differs between males and females and in addition, declines with aging. Intriguingly, skin vasodilation to local heating also requires NPY and is currently thought to be acting via a nitric oxide pathway. These studies are establishing further interest in the role of NPY as an important vasoactive agent in muscle and skin, adding to the complexity of neurovascular regulation in these tissues. In this review, we focus on the role of NPY on baseline vasomotor tone in skeletal muscle and skin and how NPY modulates vasomotor tone in response to stress, with the aim of compiling what is currently known, while highlighting some of the more pertinent questions yet to be answered.
Exercise training from late middle age until senescence does not attenuate the declines in skeletal muscle aerobic function
Authors: Betik Andrew C. , Thomas Melissa M. , Wright Kathryn J. , Riel Caitlin D. , Hepple Russell T.
Published: July 2009

We previously showed that 7 wk of treadmill exercise training in late-middle-aged rats can reverse the modest reductions in skeletal muscle aerobic function and enzyme activity relative to values in young adult rats ( Exp Physiol 93: 863–871, 2008). The purpose of the present study was to determine whether extending this training program into senescence would attenuate the accelerated decline in the muscle aerobic machinery normally seen at this advanced age. For this purpose, 29-mo-old Fisher 344 Brown-Norway rats underwent 5 or 7 mo of treadmill exercise training. Training resulted in greater exercise capacity during an incremental treadmill exercise test and reduced percent body fat in 34- and 36-mo-old rats and improved survival. Despite these benefits at the whole body level, in situ muscle aerobic capacity and muscle mass were not greater in the trained groups at 34 mo or 36 mo of age. Similarly, the trained groups did not have higher activities of citrate synthase (CS) or Complex IV in homogenates of either the plantaris (fast twitch) or the soleus (slow twitch) muscles at either age. Finally, protein expression of CS (a marker of mitochondrial content) and peroxisome proliferator-activated receptor-γ coactivator-1 (relating to the drive on mitochondrial biogenesis) were not higher in the trained groups. Therefore, although treadmill training from late middle age into senescence had significant benefits on running capacity, survival, and body fat, it did not prevent the declines in muscle mass, muscle aerobic capacity, or mitochondrial enzyme activities normally seen across this age, revealing a markedly diminished plasticity of the aerobic machinery in response to endurance exercise at advanced age.
20-HETE activates the Raf/MEK/ERK pathway in renal epithelial cells through an EGFR- and c-Src-dependent mechanism
Authors: Akbulut Talha , Regner Kevin R. , Roman Richard J. , Avner Ellis D. , Falck John R. , Park Frank
Published: July 2009

20-Hydroxyeicosatetraenoic acid (20-HETE) has been reported to promote mitogenicity in a variety of cell types, including renal epithelial cells. However, the signal transduction pathways activated by 20-HETE have not been fully defined. The present study evaluated the effects of 20-HETE and its more stable agonist analogs 20-hydroxyeicosa-5(Z),14(Z)-dienoic acid (5,14-20-HEDE) and N-[20-hydroxyeicosa-5(Z),14(Z)-dienoyl]glycine (5,14-20-HEDGE) on the Raf/MEK/ERK and phosphatidylinositol 3-kinase (PI3K)-Akt pathway in LLC-PK1renal epithelial cells. 20-HETE (20 μM) increased phosphorylation of Raf-1 (2.5 ± 0.2-fold), MEK1/2 (6.3 ± 1.6-fold), and ERK1/2 (5.8 ± 0.3-fold) compared with vehicle-treated cells. Similarly, the 20-HETE analogs also strongly activated ERK1/2 in a Raf-1- and MEK1/2-dependent manner. Moreover, 5,14-20-HEDE increased Akt phosphorylation by 2.2 ± 0.3-fold. 20-HETE and 5,14-20-HEDE also promoted activation (Y1086) of epidermal growth factor receptor (EGFR; Y1086) by 1.9 ± 0.2- and 2.5 ± 0.2-fold, respectively. These effects were completely blocked by the EGFR inhibitor EKB-569 (0.1 μM). Moreover, EKB-569 (0.1 μM), as well as a c-Src inhibitor, SKI-606 (0.05 μM), completely abolished the 20-HETE-mediated activation of the Raf/MEK/ERK and PI3K-Akt pathways. Blockade of PKC with bisindolylmaleimide I had no effect on 20-HETE-induced ERK1/2 activation. This study demonstrated that 20-HETE activated the Raf/MEK/ERK and Akt pathways in renal epithelial cells secondary to the activation of c-Src and EGFR.