bluuebunny/crossref_metadata_2025 huggingface dataset:
A NEW FUZZY NEURAL NETWORK STRATEGY OF INSULATORS CONTAMINATION DETECTION FOR POWER SYSTEM TRANSMISSION LINE
Authors: LU YUPING , YU MIN , LAI L. L. , LIN XIA
Published: March 2008

The detection of insulators contamination is difficult in power systems because many factors can influence the pollution. The contamination condition of insulators is usually estimated by detecting the root mean square (r.m.s) of surface leakage current via online-monitoring system. It ignores the influence of environmental factors, such as temperature, humidity, etc. As these factors are fuzzy-characterized, a new method based on Fuzzy Neural Network (FNN) is proposed to improve traditional insulation contamination detection. The renewed structure of FNN is put forward. The evaluation of contamination severity of insulators is achieved through FNN, which are trained by the field samples. The results prove the validity of the method proposed in the paper and can be used to eliminate the insulator from flashover fault and improve the condition-based maintenance (CBM).
CHARACTERIZATIONS OF SOME WREATH PRODUCTS OF GROUPS BY THEIR ENDOMORPHISM SEMIGROUPS
Authors: PUUSEMP PEETER
Published: March 2008

Let A be a cyclic group of order pn, where p is a prime, and B be a finite abelian group or a finite p-group which is determined by its endomorphism semigroup in the class of all groups. It is proved that under these assumptions the wreath product A Wr B is determined by its endomorphism semigroup in the class of all groups. It is deduced from this result that if A, B, A0,…, An are finite abelian groups and A0,…, An are p-groups, p prime, then the wreath products A Wr B and An Wr (…( Wr (A1 Wr A0))…) are determined by their endomorphism semigroups in the class of all groups.
RANDOM GENERATION OF FINITELY GENERATED SUBGROUPS OF A FREE GROUP
Authors: BASSINO FRÉDÉRIQUE , NICAUD CYRIL , WEIL PASCAL
Published: March 2008

We give an efficient algorithm to randomly generate finitely generated subgroups of a given size, in a finite rank free group. Here, the size of a subgroup is the number of vertices of its representation by a reduced graph such as can be obtained by the method of Stallings foldings. Our algorithm randomly generates a subgroup of a given size n, according to the uniform distribution over size n subgroups. In the process, we give estimates of the number of size n subgroups, of the average rank of size n subgroups, and of the proportion of such subgroups that have finite index. Our algorithm has average case complexity [Formula: see text] in the RAM model and [Formula: see text] in the bitcost model.
Will Chinese Medicine Come of Age to be a Global Player?
Authors: Lee Henry
Published: March 2008

This article offers possible Solution to enhance and exploit TCM's potential as a global Player through an appropriate modernization Program.
Towards a taxonomy of perceived agency in narrative game-play
Authors: Mallon Bride
Published: March 2008

Notions of agency, authorship, and interaction tend to be broadly defined. Operational specifications exemplifying their empirical existence are needed to understand where and how players affect content, structures, process or outcomes during interaction. This article presents a taxonomy of parameters influencing interaction. In it are identified (a) game aspects in which the player feels agency, and (b) game mechanisms that encourage that feeling. Such a taxonomy is useful for (i) game designers considering where and how to incorporate user input and input triggers, and (ii) evaluating the quality of interaction, given that players judge game quality partly on the extent to which their agency is enabled or inhibited. The taxonomy builds on the results of a series of focus-group studies analyzing selected commercial narrative role-play and adventure games
Modeling motivation for adaptive nonplayer characters in dynamic computer game worlds
Authors: Merrick Kathryn
Published: March 2008

Current computer games are being set in increasingly more complex and dynamic virtual environments. Massively multiplayer online games, for example, are played in persistent virtual worlds, which evolve and change as players create and personalize their own virtual property. In contrast, technologies for controlling the behavior of nonplayer characters that populate virtual game worlds are frequently limited to preprogrammed rules. Characters using fixed rule-sets lack the ability to adapt in time with their environment. Motivated reinforcement learning offers an alternative to character design that can achieve nonplayer characters that both evolve and adapt in dynamic environments. This article presents and evaluates two computational models of motivation for use in nonplayer characters in persistent computer game worlds. These models represent motivation as an ongoing search for novelty, interest, and competence. Two metrics are introduced to evaluate the adaptability of characters controlled by motivated reinforcement learning agents using different models of motivation. These metrics characterize the behavior of nonplayer characters in terms of the variety and complexity of learned behaviors. An empirical evaluation of characters in simulated game scenarios shows that characters motivated by the search for competence are more adaptable in dynamic environments than those motivated by interest and novelty alone.
FeatherTrait
Authors: Liquori Luigi , Spiwack Arnaud
Published: March 2008

In the context of
statically typed, class-based languages
, we investigate classes that can be extended with
trait
composition. A trait is a collection of methods without state; it can be viewed as an
incomplete stateless class
. Traits can be composed in any order, but only make sense when imported by a class that provides state variables and additional methods to disambiguate conflicting names arising between the imported traits. We introduce FeatherTrait Java (FTJ), a conservative extension of the simple lightweight class-based calculus Featherweight Java (FJ) with
statically typed traits
. In FTJ, classes can be built using traits as basic behavioral bricks; method conflicts between imported traits must be resolved
explicitly
by the user either by (i) aliasing or excluding method names in traits, or by (ii) overriding explicitly the conflicting methods in the class or in the trait itself. We present an operational semantics with a lookup algorithm, and a sound type system that guarantees that evaluating a well-typed expression never yields a
message-not-understood
run-time error nor gets the interpreter stuck. We give examples of the increased expressive power of the trait-based inheritance model. The resulting calculus appears to be a good starting point for a rigorous mathematical analysis of typed class-based languages featuring trait-based inheritance.
Teaching students to think nondeterministically
Authors: Armoni Michal , Lewenstein Noa , Ben-Ari Mordechai
Published: March 2008

Nondeterminism is a fundamental concept of computer science. However, since it is a very abstract concept, teaching and learning nondeterminism is difficult. In this paper we focus on one aspect of the teaching and learning processes of nondeterminism: the extent to which undergraduate students of computer science perceive that nondeterministic automata exhibit nondeterministic behavior, that is, they are unpredictable and inconsistent. First we show that students tend to think of nondeterministic automata as consistent machines; then we show that an explicit intervention can significantly affect students' mental models of nondeterministic automata in the direction of improving their perception of nondeterministic behavior.
Incorporating transformations into jflap for enhanced understanding of automata
Authors: Lucas Joan M. , Jarvis Jonathan
Published: March 2008

This paper describes our experience extending the educational software program JFLAP. JFLAP enables students to design and simulate automata such as Finite State Machines, push-down automata, and Turing Machines. It is a valuable aid in any Automata Theory course. We modified JFLAP so that students could write Java programs that alter the actual automaton itself. This utility greatly increases the students' ability to grasp such fundamental topics as the Church-Turing thesis and the theory of undecidability.
Cross-cultural issues in a tutored video instruction course
Authors: Linnell Natalie , Anderson Richard , Prey Jane
Published: March 2008

In this paper we discuss cultural issues encountered while offering an Algorithms course from a US university at a Chinese university using Tutored Video Instruction (TVI). TVI is a distance learning methodology where lectures are recorded at one site and then shown to a group of students at a remote site by Teaching Assistants (TAs) who stop the video periodically for questions and discussion. In conducting this cross-cultural class, we were interested in determining if we could overcome the issues of using English language materials for Chinese students, achieve a sense of local ownership of the course, and create an interactive classroom environment. We were generally successful in achieving these goals by providing supporting materials and working closely with the Teaching Assistants who served as facilitators.
Fair division as a means of apportioning software engineering class projects
Authors: Beck Jon
Published: March 2008

In a junior- or senior-level undergraduate software engineering course that uses real-world projects for real clients, different parts of a project are inherently unequal in difficulty, time requirements, and desirability. A perennial problem is assigning portions of the project to student teams equitably. Fair division is a highly effective strategy for making an equitable, proportional, and envy-free assignment of tasks and in serving as the basis for fair grading of assignments which vary in difficulty, desirability, and time requirements.
An early software engineering approach to teaching cs1, cs2 and ai
Authors: Rao T. M. , Mitra Sandeep
Published: March 2008

We propose the use of a new design-first approach called Problem Stereotypes and Solution Frameworks, for teaching CS1 and CS2. A problem stereotype is a category of problems that can be solved using similar techniques. A solution framework is a typical solution to a problem, parts of which can be reused to solve other problems of this stereotype. Students are introduced to a stereotype through a selection of related problems, and common features among these are identified. Homework problems are selected from the same stereotype, with students expected to follow the "recipe" provided by the given examples to generate their own solutions. Using this approach reduces the stress level for beginner students, and prevents them falling prey to the "CS is HARD" myth. We present the results of our experience with this approach in two introductory classes and an upper-division Artificial Intelligence (AI) class at SUNY Brockport.
Mock trials and role-playing in computer ethics courses
Authors: Canosa Roxanne L. , Lucas Joan M.
Published: March 2008

Mock trials are an effective and fun way of eliciting thoughtful dialogue from students, and encouraging them to produce incisive analyses of current ethical dilemmas related to computers and society. This paper describes our experience using mock trials in two computer ethics courses. Each trial was centered on a specific

controversial and ethically or legally ambiguous topic related to current computer usage in society. Students participated in a series of mock trials during the term, alternating their role in each trial between jury, proponent, and opponent. Class participation was nearly 100% for every trial, with many students electing to

define their own sub-role within their assigned major role. The logistics of the trials were initially difficult to administer and monitor; however, they quickly became manageable as we gained more experience with the opportunities and pitfalls associated with the mock-trial system, and as students volunteered suggestions for improvements.
Backstop
Authors: Murphy Christian , Kim Eunhee , Kaiser Gail , Cannon Adam
Published: March 2008

The errors that Java programmers are likely to encounter can roughly be categorized into three groups: compile-time (semantic and syntactic), logical, and runtime (exceptions). While much work has focused on the first two, there are very few tools that exist for interpreting the sometimes cryptic messages that result from runtime errors. Novice programmers in particular have difficulty dealing with uncaught exceptions in their code and the resulting stack traces, which are by no means easy to understand. We present Backstop, a tool for debugging runtime errors in Java applications. This tool provides more user-friendly error messages when an uncaught exception occurs, and also provides debugging support by allowing users to watch the execution of the program and the changes to the values of variables. We also present the results of two preliminary studies conducted on introductory-level programmers using the two different features of the tool.
An experimental laboratory environment for teaching embedded operating systems
Authors: Brylow Dennis
Published: March 2008

This paper describes Marquette University's efforts to build an experimental embedded systems laboratory for hands-on projects in an operating systems course. Our prototype laboratory is now serving as the basis for a coherent sequence of class projects threaded throughout courses in hardware systems, operating systems, networking, and embedded systems. We describe the major components of our Embedded XINU laboratory environment, the operating systems course, and related improvements in other core courses of our curriculum.
An experimental study of cooperative learning in cs1
Authors: Beck Leland L. , Chizhik Alexander W.
Published: March 2008

An experiment was conducted to study the effectiveness of the cooperative learning approach to teaching CS1. The cooperative learning exercises, which used specific roles to focus students' attention on key concepts, were designed so they could be used in a variety of educational settings. Experimental results show that the benefits of cooperative learning clearly outweighed any possible losses due to reduced lecture time. These benefits were enjoyed by both male and female students, and by students from a variety of majors. Majority and minority students performed at approximately the same overall level when using the cooperative learning approach. There are indications that the educational benefits continue when students who had a cooperative learning experience in CS1 go on to CS2.
A story-centered, learn-by-doing approach to software engineering education
Authors: Bareiss Ray , Griss Martin
Published: March 2008

Carnegie Mellon's West Coast Campus offers an MS in Software Engineering, with technical and development management tracks, targeted at working software professionals in Silicon Valley. We believe the program to be unique in that it is entirely team-based and project-centered. Students learn by doing as they are coached just in time by faculty in the context of authentic projects, and they are evaluated based on what they produce. Student satisfaction is high: 92% believe that the program has given them a competitive advantage with respect to their professional peers, and their promotion and salary histories bear out this belief.
Patterns for programming in parallel, pedagogically
Authors: Jadud Matthew C. , Simpson Jon , Jacobsen Christian L.
Published: March 2008

Pipeline, Delta, and Black Hole are three simple patterns used in concurrent software design. We recently presented these and other patterns for parallelism at a nine-hour workshop for professional embedded systems developers. By grounding these patterns in the context of robotic control on the LEGO Mindstorms, we provided an engaging and enjoyable educational experience for our "students," and reaffirmed that small, powerful languages have a place in education for beginners and experts alike.
Automatic extraction of notions from course material
Authors: Pedroni Michela , Oriol Manuel , Meyer Bertrand , Angerer Lukas
Published: March 2008

Formally defining the knowledge units taught in a course helps instructors ensure a sound coverage of topics and provides an objective basis for comparing the content of two courses. The main issue is to list and define the course concepts, down to basic knowledge units. Ontology learning techniques can help partially automate the process by extracting information from existing materials such as slides and textbooks. The TrucStudio course planning tool, discussed in this article, provides such support and relies on Text2Onto to extract concepts from course material. We conducted experiments on two different programming courses to assess the quality of the results.
A model for high school computer science education
Authors: Hazzan Orit , Gal-Ezer Judith , Blum Lenore
Published: March 2008

This paper presents a model program for high school computer science education. It is based on an analysis of the structure of the Israeli high school computer science curriculum considered to be one of the leading curricula worldwide. The model consists of four key elements as well as interconnections between these elements. It is proposed that such a model be considered and/or adapted when a country wishes to implement a nation-wide program for high school computer science education.
Broadening participation through scalable game design
Authors: Repenning Alexander , Ioannidou Andri
Published: March 2008

Game development is quickly gaining popularity in introductory programming courses. Motivational and educational aspects of game development are hard to balance and often sacrifice principled educational goals. We are employing the notion of scalable game design as an approach to broaden participation by shifting the pedagogical focus from specific programming to more general design comprehension. Scalable game design combines the Flow psychological model, the FIT competency framework and the AgentSheets rapid game prototyping environment. The scalable aspect of our approach has allowed us to teach game design in a broad variety of contexts with students ranging from elementary school to CS graduate students, with projects ranging from simple Frogger-like to sophisticated Sims-like games, and with diverse cultures from the USA, Europe and Asia.
Ucigame, a java library for games
Authors: Frost Daniel
Published: March 2008

Ucigame (pronounced
OO-see-GAH-me
) is a Java package that supports the programming of 2D sprite-based computer games. Designed for novice programmers, it enables students in an introductory class to write computer games that have animated sprites, music and sound effects, and event-driven keyboard and mouse handling. Ucigame has also been used successfully in a senior-level class for experienced programmers.
Community connections
Authors: Brooks Christopher H.
Published: March 2008

This paper describes Community Connections, an ongoing service-learning project at the University of San Francisco aimed at bridging the digital divide. We discuss Community Connections' work both in San Francisco and in Peru, the advantages and learning outcomes of incorporating service-learning into a traditional computer science curriculum, outline some of the pitfalls and challenges in implementing this program, and provide advice for implementing technology-oriented service-learning programs at other institutions based on our experiences.
Cultural representations of gender among u. s. computer science undergraduates
Authors: Lopez Antonio M. , Zhang Kun , Lopez Frederick G.
Published: March 2008

Worldwide, there is substantial evidence that cultural contexts may either support or hinder the number of women versus men participating in computing. There is also evidence that certain computing disciplines have more appeal to women than others. Hence research on any computing gender gap should be specific to a culture and a computing discipline. In the United States (US) a popular belief is that Computer Science (CS) has a decidedly 'masculine culture'. This paper reports on research that investigates this perception, comparing CS undergraduates to undergraduates in non-computing disciplines (NCD). The data were collected in a nationwide purposeful sampling of US citizens attending Historically Black Colleges and Universities (HBCUs) and Predominantly White Institutions (PWIs) with an ethnic compositional focus on African Americans and Caucasians. The paper describes a survey scale developed in the US to characterize a person's gender role as feminine, masculine, or androgynous. The data were analyzed using statistical and data mining techniques. Surprisingly, CS students were found to be more androgynous than masculine.
Helping him see
Authors: Califf Mary Elaine , Goodwin Mary M. , Brownell Jake
Published: March 2008

In this paper, we describe some of the challenges of teaching computer science to a visually impaired student along with suggested solutions for these challenges. We include perspectives of both professors and a severely visually impaired student.
An image background detection project for a visual exploration of DFS and BFS
Authors: Erkan Ali , Gochev Diyan
Published: March 2008

We outline a Data Structures project that visualizes the operation of depth first search (DFS) and breadth first search (BFS). We use color to illustrate how these two techniques differ as they traverse a search space. We present additional exercises that outline how students can further explore the underlying data structures, algorithmic concepts, and efficiency issues. We also provide a limited amount of student assessment to gauge the effectiveness of our approach.
The funnel that grew our cis major in the cs desert
Authors: Pearce Janice , Nakazawa Mario
Published: March 2008

Across the US, plummeting CS enrollments and disappointing student retention have caused serious concern in recent years. Yet, in the Spring of 2007, the Berea College faculty unanimously adopted a CIS major in response to the rise in enrollment in CS0 and retention into CS1. This paper details how using a funnel approach to attract students into the discipline via multiple CS0-level courses resulted in the exception to the trend.
Supporting student-written tests of gui programs
Authors: Thornton Matthew , Edwards Stephen H. , Tan Roy P. , Pérez-Quiñones Manuel A.
Published: March 2008

Tools like JUnit and its relatives are making software testing reachable even for introductory students. At the same time, however, many introductory computer sciences courses use graphical interfaces as an "attention grabber" for students and as a metaphor for teaching object-oriented programming. Unfortunately, developing software tests for programs that have significant graphical user interfaces is beyond the abilities of typical students (and, for that matter, many educators). This paper describes a framework for combining readily available tools to create an infrastructure for writing tests for Java programs that have graphical user interfaces. These tests are level-appropriate for introductory students and fit in with current approaches in computer science education that incorporate testing in programming assignments. An analysis of data collected during actual student use of the framework in a CS1 course is presented.
Toward a Biomechanical Understanding of Whole Bacterial Cells
Authors: Morris Dylan M. , Jensen Grant J.
Published: March 2008

Following decades of research in genetics and biochemistry, the basic metabolism of bacteria is now well understood. In addition to core metabolism, however, bacterial cells also perform a number of mechanical tasks such as maintaining a characteristic shape, moving within their environment, segregating their genome, and dividing. Major advances in imaging technologies including fluorescence light microscopy (fLM) and electron cryotomography (ECT) have provided new insight into the bacterial ultrastructures that accomplish these tasks. It is now clear, for instance, that bacteria are highly organized, possessing cytoskeletons, specifically arranged genomes, internal compartments, and carefully positioned macromolecular machines. These structures and their functions are reviewed here in the form of a progress report toward a complete biomechanical understanding of a generalized bacterial cell. The goal of eventually integrating genetic, biochemical, imaging, and biophysical data into spatially explicit, mechanically predictive models of whole cells is highlighted.
Fat and Beyond: The Diverse Biology of PPARγ
Authors: Tontonoz Peter , Spiegelman Bruce M.
Published: March 2008

The nuclear receptor PPARγ is a ligand-activated transcription factor that plays an important role in the control of gene expression linked to a variety of physiological processes. PPARγ was initially characterized as the master regulator for the development of adipose cells. Ligands for PPARγ include naturally occurring fatty acids and the thiazolidinedione (TZD) class of antidiabetic drugs. Activation of PPARγ improves insulin sensitivity in rodents and humans through a combination of metabolic actions, including partitioning of lipid stores and the regulation of metabolic and inflammatory mediators termed adipokines. PPARγ signaling has also been implicated in the control of cell proliferation, atherosclerosis, macrophage function, and immunity. Here, we review recent advances in our understanding of the diverse biological actions of PPARγ with an eye toward the expanding therapeutic potential of PPARγ agonist drugs.
Non-Chromate Inhibition of Magnesium Corrosion in Chloride Containing Electrolyte
Authors: Williams Geraint , McMurray H. N.
Published: March 2008

An in-situ Scanning Vibrating Electrode Technique (SVET) is used to investigate the inhibition of localized corrosion occurring on unpolarised magnesium (Mg) samples immersed in 5% w/v aqueous sodium chloride electrolyte. In uninhibited electrolyte, localized corrosion features taking the form of dark, radially expanding discs are shown to consist of a strongly cathodic interior, surrounded by a ring of anodic activity. Of the various inhibitors tested, only chromate and phosphate additions markedly decrease the extent of localized corrosion observed, with the onset of profound corrosion inhibition achieved at threshold concentrations of 10-2 and 2x10-4 mol dm-3 respectively. Phosphate inhibition efficiency increases perceptibly when the pH of the electrolyte is decreased. Consequently at [PO43-] ≥ 10-3 mol dm-3, in the pH 4 - 7 range, Mg is able to withstand over 5h immersion with little evidence of breakdown.
Microstructural Evaluations of Oxide Films During Spark Anodizing of Mg-Al Alloy in Alkaline Fluoride Electrolytes
Authors: Wang Lishi , Pan Chunxu , Cai Qizhou , Wei Bokang
Published: March 2008

Spark anodizing (SA) has been developed as a novel technique for corrosion protection by forming a ceramic layer on magnesium alloys, in which the fluoride in the electrolyte recipes plays a key role during coating. In the present work, the SA ceramic layer produced on AZ91D magnesium alloy was characterized by using SEM, TEM and EDS. The results showed that: 1) there was a fluoride enriched zone around 1-2μm in thickness at the coating/substrate interface, which was composed of the amorphous substrate, nanocrystal MgO particles sized in 20-60nm and sealed cavities; 2) the oxygen content in the inner layer was higher than that in the outer layer, while the fluorine content was relative even in both layers, which suggested that the barrier layer was included in this fluoride zone, and that the fluorine may be only a retained marker during the formation of new coating materials.
Improvement of the Oxidation Resistance of TiAl Alloys Using Controlled Gaseous Fluorination
Authors: Masset Patrick J. , Schütze Michael
Published: March 2008

Surface fluorination of TiAl alloys was carried out using fluorine arising from the thermal decomposition of CFn compounds. From thermodynamic calculations it was shown that the halogen effect is effective despite the presence of a small amount of carbon (from CFn decomposition). Oxidation tests at 900 {degree sign}C over 1000 h were carried out with γ-MET alloy and showed the beneficial effect of the surface treatment using CFn compounds as fluorine source.
Estimation of Inhibitor Efficiency against Hydrogen Sulfide and Carbonic Acid Corrosion of Carbon Steel by Impedance Spectroscopy Method
Authors: Vigdorovich Vladimir , Tsygankova Liudmila E. , Siniutina Svetlana , Kichigin Vladimir
Published: March 2008

Investigation of the protective efficiency of technological mixture of pyridine bases, its solution in heavy coal solvent and 1-(3,6-diazo-8-amino)-2-(alkyl of tall oil acids)-1,3-diazo- 2-cyclopentene (EM-9) against carbon steel corrosion in chloride media with pH equal to 2 and 4 has been conducted by impedance spectroscopy method. The electrochemical impedance spectroscopy measurements (Solartron) were carried out in the frequency range 60 kHz - 10 mHz at the corrosion potential. Protective effect of the inhibitors (Z,%) was calculated on data of the resistance of charge transfer in anodic reaction. The investigated inhibitors are more effective in the solutions containing H2S or H2S and CO2 together at pH=2. Their protective efficiency is equal to 80 - 85% at the inhibitor concentration equal to 100 mg/l. The obtained values satisfactorily correlate with values of Z calculated on data of the gravimetrical corrosion tests. Protecti ve efficiency of the inhibitors increases with pH decrease.
All-Optical Fuel Leak Detector for Monomethylhydrazine
Authors: Sampathkumaran Uma , Barry Barbara , Tseng Derek , Mushfiq Mohammad , Viswanathan Subbu , Majumdar Arun , Goswami Kisholoy
Published: March 2008

Hydrazine-based fuels are commonly used in missiles, spacecraft and space launch vehicles. These chemicals are extremely toxic, highly energetic, and consequentially very hazardous. Currently, monomethylhydrazine (MMH) is considered to be the predominant fuel for spontaneous ignition. The current threshold limit value (TLV) is established at 10 ppb by the American Conference of Governmental Industrial Hygienists (ACGIH). Therefore, monitoring leakage of these chemicals in ambient air becomes highly important for compliance monitoring. InnoSense LLC's (ISL) all-optical leak detector can be calibrated to detect leaks in the parts-per-million to parts-per-billion range. ISL's innovative sensor device incorporates a self-referenced, fiber-optics-based sensor platform for detecting MMH from -46{degree sign}C to +71{degree sign}C. Additionally, an optical sensor system can decrease payload in space applications, and be networked to monitor multiple locations in situ and in real time. This paper discusses the use of an organically modified silicate (Ormosil) matrix to develop the optical leak detector for MMH.
Induction of HIF-2α is dependent on mitochondrial O2 consumption in an O2-sensitive adrenomedullary chromaffin cell line
Authors: Brown Stephen T. , Nurse Colin A.
Published: March 2008

During low O2 (hypoxia), hypoxia-inducible factor (HIF)-α is stabilized and translocates to the nucleus, where it regulates genes critical for survival and/or adaptation in low O2. While it appears that mitochondria play a critical role in HIF induction, controversy surrounds the underlying mechanism(s). To address this, we monitored HIF-2α expression and oxygen consumption in an O2-sensitive immortalized rat adrenomedullary chromaffin (MAH) cell line. Hypoxia (2–8% O2) caused a concentration- and time-dependent increase in HIF-2α induction, which was blocked in MAH cells with either RNA interference knockdown of the Rieske Fe-S protein, a component of complex III, or knockdown of cytochrome- c oxidase subunit of complex IV, or defective mitochondrial DNA (ρ0 cells). Additionally, pharmacological inhibitors of mitochondrial complexes I, III, IV, i.e., rotenone (1 μM), myxothiazol (1 μM), antimycin A (1 μg/ml), and cyanide (1 mM), blocked HIF-2α induction in control MAH cells. Interestingly, the inhibitory effects of the mitochondrial inhibitors were dependent on O2 concentration such that at moderate-to-severe hypoxia (6% O2), HIF-2α induction was blocked by low inhibitor concentrations that were ineffective at more severe hypoxia (2% O2). Manipulation of the levels of reactive oxygen species (ROS) had no effect on HIF-2α induction. These data suggest that in this O2-sensitive cell line, mitochondrial O2 consumption, rather than changes in ROS, regulates HIF-2α during hypoxia.
Thrombin-induced endothelial barrier disruption in intact microvessels: role of RhoA/Rho kinase-myosin phosphatase axis
Authors: van Nieuw Amerongen G. P. , Musters R. J. P. , Eringa E. C. , Sipkema P. , van Hinsbergh V. W. M.
Published: March 2008

Endothelial hyperpermeability is regulated by a myosin light chain-2 (MLC2) phosphorylation-dependent contractile mechanism. Thrombin is a potent inducer of hyperpermeability of cultured monolayers of endothelial cells (ECs) via Rho kinase-mediated MLC2-phosphorylation. The aim of the present study was to investigate the effects of thrombin on in situ endothelial morphology and barrier integrity. Cytoskeletal dynamics, regions of paracellular flux, and MLC2-phosphorylation of ECs were visualized by digital three-dimensional imaging microscopy of pressurized rat kidney arterioles. Myosin phosphatase targeting subunit (MYPT1)-phosphorylation was used as a surrogate marker for Rho kinase activity. Thrombin induced the formation of F-actin filaments in ECs in situ and rounding of the ECs in the absence of obvious formation of gaps between ECs. These changes were accompanied by an increase in MLC2 phosphorylation and a decrease in barrier integrity. In vitro analysis revealed that Rho kinase activity on F-actin filaments was associated with a contractile response that enhanced opening of the barrier. Rho kinase activity was not detectable on F-actin filaments induced by histamine, an inducer of a more transient hyperpermeability response. Inhibition of the myosin phosphatase mimicked the effects of thrombin on barrier function. The thrombin-induced changes in in situ MLC2 phosphorylation and barrier function were Rho kinase dependent. These data demonstrate a direct effect of thrombin on EC morphology and barrier integrity in intact microvessels. Furthermore, they establish an important contribution of enhanced Rho kinase activity to the development of prolonged but not transient types of endothelial barrier dysfunction.
Endogenous interferon-γ is required for efficient skeletal muscle regeneration
Authors: Cheng Ming , Nguyen Mai-Huong , Fantuzzi Giamila , Koh Timothy J.
Published: March 2008

The inflammatory response is thought to play important roles in tissue healing. The hypothesis of this study was that the inflammatory cytokine interferon (IFN)-γ is produced endogenously following skeletal muscle injury and promotes efficient healing. We show that IFN-γ is expressed at both mRNA and protein levels in skeletal muscle following injury, and that the time course of IFN-γ expression correlated with the accumulation of macrophages, T-cells, and natural killer cells, as well as myoblasts, in damaged muscle. Cells of each type were isolated from injured muscle, and IFN-γ expression was detected in each cell type. We also demonstrate that administration of an IFN-γ receptor blocking antibody to wild-type mice impaired induction of interferon response factor-1, reduced cell proliferation, and decreased formation of regenerating fibers. IFN-γ null mice showed similarly impaired muscle healing associated with impaired macrophage function and development of fibrosis. In vitro studies demonstrated that IFN-γ and its receptor are expressed in the C2C12 muscle cell line, and that the IFN-γ receptor blocking antibody reduced proliferation and fusion of these muscle cells. In summary, our results indicate that IFN-γ promotes muscle healing, in part, by stimulating formation of new muscle fibers.
Cortisol and corticosterone in the songbird immune and nervous systems: local vs. systemic levels during development
Authors: Schmidt Kim L. , Soma Kiran K.
Published: March 2008

Glucocorticoids (GCs) have profound effects on the immune and nervous systems during development. However, circulating GC levels are low neonatally and show little response to stressors. This paradox could be resolved if immune and neural tissues locally synthesize GCs. Here, we measured baseline corticosterone and cortisol levels in plasma, immune organs, and brain regions of developing zebra finches. Steroids were extracted using solid phase-extraction and quantified using specific immunoassays. As expected, corticosterone was the predominant GC in plasma and increased with age. In contrast, cortisol was the predominant GC in immune tissues (bursa of Fabricius, thymus, spleen) and decreased with age. Cortisol levels in immune tissues were higher than cortisol levels in plasma. In the brain, corticosterone and cortisol levels were similarly low, providing little evidence for local synthesis of GCs in the brain. This is the first study to measure 1) cortisol in the plasma of songbirds, 2) corticosterone or cortisol in the brain of songbirds, and 3) corticosterone or cortisol in the immune system of any species. Despite the prevailing dogma that corticosterone is the primary GC in birds, these results indicate that cortisol is the predominant GC in the immune system of developing zebra finches. These results raise the hypothesis that cortisol is synthesized de novo from cholesterol in the immune system as an “immunosteroid,” analogous to neurosteroids synthesized in the brain. Local production of GCs in immune tissues may allow GCs to regulate lymphocyte selection while avoiding the costs of high systemic GCs during development.
Benefits of oat β-glucan on respiratory infection following exercise stress: role of lung macrophages
Authors: Murphy E. A. , Davis J. M. , Brown A. S. , Carmichael M. D. , Carson J. A. , Van Rooijen N. , Ghaffar A. , Mayer E. P.
Published: March 2008

Exercise stress is associated with an increased risk for upper respiratory tract infection (URTI). We have shown that consumption of the soluble oat fiber β-glucan (OβG) can offset the increased risk for infection and decreased macrophage antiviral resistance following stressful exercise; however, the direct role of macrophages is unknown. This study examined the effect of macrophage depletion on the benefits of orally administered OβG on susceptibility to infection (morbidity, symptom severity, and mortality) following exercise stress. CL2MDP (Ex- H2O-CL2MDP, Ex-OβG-CL2MDP, Con-H2O-CL2MDP, Con-OβG-CL2MDP)-encapsulated liposomes were administered intranasally to deplete macrophages, and PBS (Ex-H2O-PBS, Ex-OβG-PBS, Con-H2O-PBS, Con-OβG-PBS)-encapsulated liposomes were given to macrophage-intact groups. Ex mice ran to volitional fatigue on a treadmill for 3 consecutive days, and OβG mice were fed a solution of 50% OβG in their drinking water for 10 consecutive days before infection. Fifteen minutes following the final bout of Ex or rest, mice were intranasally inoculated with 50 μl of a standardized dose of herpes simplex virus-1. Ex increased morbidity ( P < 0.001) and symptom severity ( P < 0.05) but not mortality ( P = 0.09). The increase in morbidity and symptom severity was blocked by OβG consumption for 10 consecutive days before exercise and infection [morbidity ( P < 0.001) and symptom severity ( P < 0.05)]. Depletion of macrophages negated the beneficial effects of OβG on reducing susceptibility to infection following exercise stress, as evidenced by an increase in morbidity ( P < 0.01) and symptom severity ( P < 0.05). Results indicate that lung macrophages are at least partially responsible for mediating the beneficial effects of OβG on susceptibility to respiratory infection following exercise stress.
Smad ubiquitination regulatory factor-2 in the fibrotic kidney: regulation, target specificity, and functional implication
Authors: Tan Ruoyun , He Weichun , Lin Xia , Kiss Lawrence P. , Liu Youhua
Published: March 2008

Smad ubiquitination regulatory factor-2 (Smurf2) is an E3 ubiqutin ligase that plays a pivotal role in regulating TGF-β signaling via selectively targeting key components of the Smad pathway for degradation. In this study, we have investigated the regulation of Smurf2 expression, its target specificity, and the functional implication of its induction in the fibrotic kidney. Immunohistochemical staining revealed that Smurf2 was upregulated specifically in renal tubules of kidney biopsies from patients with various nephropathies. In vitro, Smurf2 mRNA and protein were induced in human proximal tubular epithelial cells (HKC-8) upon TGF-β1 stimulation. Ectopic expression of Smurf2 was sufficient to reduce the steady-state levels of Smad2, but not Smad1, Smad3, Smad4, and Smad7, in HKC-8 cells. Interestingly, Smurf2 was also able to downregulate the Smad transcriptional corepressors Ski, SnoN, and TG-interacting factor. Inhibition of the proteasomal pathway prevented Smurf2-mediated downregulation of Smad2 and Smad corepressors. Functionally, overexpression of Smurf2 enhanced the transcription of the TGF-β-responsive promoter and augmented TGF-β1-mediated E-cadherin suppression, as well as fibronectin and type I collagen induction in HKC-8 cells. These results indicate that Smurf2 specifically targets both positive and negative Smad regulators for destruction in tubular epithelial cells, thereby providing a complex fine-tuning of TGF-β signaling. It appears that dysregulation of Smurf2 could contribute to an aberrant TGF-β/Smad signaling in the pathogenesis of kidney fibrosis.
Updating Target Distance Across Eye Movements in Depth
Authors: Van Pelt Stan , Medendorp W. Pieter
Published: March 2008

We tested between two coding mechanisms that the brain may use to retain distance information about a target for a reaching movement across vergence eye movements. If the brain was to encode a retinal disparity representation (retinal model), i.e., target depth relative to the plane of fixation, each vergence eye movement would require an active update of this representation to preserve depth constancy. Alternatively, if the brain was to store an egocentric distance representation of the target by integrating retinal disparity and vergence signals at the moment of target presentation, this representation should remain stable across subsequent vergence shifts (nonretinal model). We tested between these schemes by measuring errors of human reaching movements ( n = 14 subjects) to remembered targets, briefly presented before a vergence eye movement. For comparison, we also tested their directional accuracy across version eye movements. With intervening vergence shifts, the memory-guided reaches showed an error pattern that was based on the new eye position and on the depth of the remembered target relative to that position. This suggests that target depth is recomputed after the gaze shift, supporting the retinal model. Our results also confirm earlier literature showing retinal updating of target direction. Furthermore, regression analyses revealed updating gains close to one for both target depth and direction, suggesting that the errors arise after the updating stage during the subsequent reference frame transformations that are involved in reaching.
Stability and Variability: Indicators for Passive Stability and Active Control in a Rhythmic Task
Authors: Wei Kunlin , Dijkstra Tjeerd M. H. , Sternad Dagmar
Published: March 2008

Using a rhythmic task where human subjects bounced a ball with a handheld racket, fine-grained analyses of stability and variability extricated contributions from open-loop control, noise strength, and active error compensation. Based on stability analyses of a stochastic-deterministic model of the task—a surface contacting the ball by periodic movements—open-loop or dynamic stability was assessed by the acceleration of the racket at contact. Autocovariance analyses of model and data were further used to gauge the contributions of open-loop stability and noise strength. Variability and regression analyses estimated active error compensation. Empirical results demonstrated that experienced actors exploited open-loop stability more than novices, had lower noise strength, and applied more active error compensations. By manipulating the model parameter coefficient of restitution, task stability was varied and showed that actors graded these three components as a function of task stability. It is concluded that actors tune into task stability when stability is high but use more active compensation when stability is reduced. Implications for the neural underpinnings for passive stability and active control are discussed. Further, results showed that stability and variability are not simply the inverse of each other but contain more quantitative information when combined with model analyses.
Uncoupling protein 1 expression in murine skeletal muscle increases AMPK activation, glucose turnover, and insulin sensitivity in vivo
Authors: Neschen Susanne , Katterle Yvonne , Richter Julia , Augustin Robert , Scherneck Stephan , Mirhashemi Farshad , Schürmann Annette , Joost Hans-Georg , Klaus Susanne
Published: March 2008

Uncoupling of oxidative phosphorylation represents a potential target for the treatment of hyperglycemia and insulin resistance in obesity and type 2 diabetes. The present study investigated whether the expression of uncoupling protein 1 in skeletal muscles of transgenic (mUCP1 TG) mice modulates insulin action in major insulin target tissues in vivo. Euglycemic-hyperinsulinemic clamps (17 pM·kg lean body mass−1·min−1) were performed in 9-mo-old hemizygous male mUCP1 TG mice and wild-type (WT) littermates matched for body composition. mUCP1 TG mice exhibited fasting hypoglycemia and hypoinsulinemia compared with WT mice, whereas fasting hepatic glucose production rates were comparable in both genotypes. mUCP1 TG mice were markedly more sensitive to insulin action compared with WT mice and displayed threefold higher glucose infusion rates, enhanced skeletal muscle and white adipose tissue glucose uptake, and whole body glycolysis rates. In the absence of alterations in plasma adiponectin concentrations, acceleration of insulin-stimulated glucose turnover in skeletal muscle of mUCP1 TG mice was accompanied by increased phosphorylated Akt-to-Akt and phosphorylated AMP-activated protein kinase (AMPK)-to-AMPK ratios compared with WT mice. UCP1-mediated uncoupling of oxidative phosphorylation in skeletal muscle was paralleled by AMPK activation and thereby stimulated insulin-mediated glucose uptake in skeletal muscle.
Molecular Aspects ofPlasmodium falciparumInfection during Pregnancy
Authors: Ndam Nicaise Tuikue , Deloron Philippe
Published: March 2008

Cytoadherence ofPlasmodium-falciparum-parasitized red blood cells (PRBCs) to host receptors is the key phenomenon in the pathological process of the malaria disease. Some of these interactions can originate poor outcomes responsible for 1 to 3 million annual deaths mostly occurring among children in sub-Saharan Africa. Pregnancy-associated malaria (PAM) represents an important exception of the disease occurring at adulthood in malaria endemic settings. Consequences of this are shared between the mother (maternal anemia) and the baby (low birth weight and infant mortality). Demonstrating that parasites causing PAM express specific variant surface antigens (VSAPAM), including theP. falciparumerythrocyte membrane protein 1 (PfEMP1) variant VAR2CSA, that are targets for protective immunity has strengthened the possibility for the development of PAM-specific vaccine. In this paper, we review the molecular basis of malaria pathogenesis attributable to the erythrocyte stages of the parasites, and findings supporting potential anti-PAM vaccine components evidenced in PAM.