bluuebunny/crossref_metadata_2025 huggingface dataset:
Inferring aliasing and encapsulation properties for java
Authors: Ma Kin-Keung , Foster Jeffrey S.
Published: November 2007

There are many proposals for language techniques to control aliasing and encapsulation in object oriented programs, typically based on notions of object ownership and pointer uniqueness. Most of these systems require extensive manual annotations, and thus there is little experience with these properties in large, existing Java code bases. To remedy this situation, we present Uno, a novel static analysis for automatically inferring ownership, uniqueness, and other aliasing and encapsulation properties in Java. Our analysis requires no annotations, and combines an intraprocedural points-to analysis with an interprocedural, demand-driven predicate resolution algorithm. We have applied Uno to a variety of Java applications and found that some aliasing properties, such as temporarily lending a reference to a method, are common, while others, in particular field and argument ownership, are relatively uncommon. As a result, we believe that Uno can be a valuable tool for discovering and understanding aliasing and encapsulation in Java programs.
Lost in translation
Authors: Bierman Gavin M. , Meijer Erik , Torgersen Mads
Published: November 2007

Current real-world software applications typically involve heavy use of relational and XML data and their query languages. Unfortunately object-oriented languages and database query languages are based on different semantic foundations and optimization strategies. The resulting ''ROX (Relations, Objects, XML) impedance mismatc'' makes life very difficult for developers.

Microsoft Corporation is developing extensions to the .NET framework to facilitate easier processing of non-object-oriented data models. Part of this project (known as "LINQ") includes various extensions to the .NET languages to leverage this support.

In this paper we consider proposals for C
#
3.0, the next version of the C
#
programming language. We give both an informal introduction to the new language features, and a precise formal account by defining a translation from C
#
3.0 to C
#
2.0. This translation also demonstrates how these language extensions do not require any changes to the underlying CLR.
The java module system
Authors: Strniša Rok , Sewell Peter , Parkinson Matthew
Published: November 2007

Java has no module system. Its
packages
only subdivide the class name space, allowing only a very limited form of component-level information hiding and reuse. Two Java Community Processes have started addressing this problem: one describes the runtime system and has reached an early draft stage, while the other considers the developer's view and only has a straw-man proposal. Both are natural language documents, which inevitably contain ambiguities.

In this work we design and formalize a core module system for Java. Where the JCP documents are complete, we follow them closely; elsewhere we make reasonable choices. We define the syntax, the type system, and the operational semantics of an
LJAM
language, defining these rigorously in the Isabelle/HOL automated proof assistant. Using this formalization, we identify various issues with the module system. We highlight the underlying design decisions, and discuss several alternatives and their benefits. Our Isabelle/HOL definitions should provide a basis for further consideration of the design alternatives, for reference implementations, and for proofs of soundness.
Using hpm-sampling to drive dynamic compilation
Authors: Buytaert Dries , Georges Andy , Hind Michael , Arnold Matthew , Eeckhout Lieven , De Bosschere Koen
Published: November 2007

All high-performance production JVMs employ an adaptive strategy for program execution. Methods are first executed unoptimized and then an online profiling mechanism is used to find a subset of methods that should be optimized during the same execution. This paper empirically evaluates the design space of several profilers for initiating dynamic compilation and shows that existing online profiling schemes suffer from several limitations. They provide an insufficient number of samples, are untimely, and have limited accuracy at determining the frequently executed methods. We describe and comprehensively evaluate HPM-sampling, a simple but effective profiling scheme for finding optimization candidates using hardware performance monitors (HPMs) that addresses the aforementioned limitations. We show that HPM-sampling is more accurate; has low overhead; and improves performance by 5.7% on average and up to 18.3% when compared to the default system in Jikes RVM, without changing the compiler.
No ifs, ands, or buts
Authors: Edwards Jonathan
Published: November 2007

Schematic tables
are a new representation for conditionals. Roughly a cross between decision tables and data flowgraphs, they represent computation and decision-making orthogonally. They unify the full range of conditional constructs, from if statements through pattern matching to polymorphic predicate dispatch. Program logic is maintained in a declarative canonical form that enforces completeness and disjointness among choices. Schematic tables can beused either as a code specification/generation tool, or as a self-contained diagrammatic programming language. They give program logic the clarity of truth tables, and support high-level direct manipulation of that logic, avoiding much of the mental computation demanded by conventional conditionals.
Does data warehouse end-user metadata add value?
Authors: Foshay Neil , Mukherjee Avinandan , Taylor Andrew
Published: November 2007

Many data warehouses are currently underutilized by managers and knowledge workers. Can high-quality end-user metadata help to increase levels of adoption and use?
Making knowledge work in virtual teams
Authors: Thomas Dominic M. , Bostrom Robert P. , Gouge Marianne
Published: November 2007

"I've been working in computers for years, and only the simplest stuff works 90% of the time."---A virtual team leader reflecting on technology facilitation.
The choice uncertainty principle
Authors: Denning Peter J.
Published: November 2007

It is impossible to make an unambiguous choice between near-simultaneous events under a deadline. How can computations choose reliably?
A research project with important practitioner-oriented findings
Authors: Glass Robert L.
Published: November 2007

Exploring a standard that, in the end, "...fails to achieve its objectives and be useful to its users."
Stop the numbers game
Authors: Parnas David Lorge
Published: November 2007

Counting papers slows the rate of scientific progress.
Experimental algorithmics
Authors: McGeoch Catherine C.
Published: November 2007

Theoretical questions and motivations, combined with empirical research methods, produce insights into algorithm and program performance.
Empirical studies to build a science of computer science
Authors: Basili Victor R. , Zelkowitz Marvin V.
Published: November 2007

We learn to develop software by building, testing, and evolving models.
From the editors
Authors: Stafford Tom , Chau Patrick Y. K. , Schwarz Andrew , Lanier Clinton R.
Published: November 2007

Interesting times and interesting research at Data Base this year. We'll be providing coverage of a new Chinese Information Systems conference, courtesy of Global Co-Editor Patrick Chau. We have an issue on software testing in process with Al Hevner, and this promises to provide some interesting new perspectives on an underutilized but critical research area in our field.

We are expanding our global reach and service dramatically. You'll see important colleagues from distant lands on our masthead as board members, even editors. You'll notice increasing submissions from far parts of the global market. You'll find a new perspective on the practice of scholarship in Information Systems, worldwide, at ACM Data Base!

This issue, welcome Guest Editor Ed Roche, who has brought a globe-spanning body of speculative and futuristic writing about emerging virtual worlds enabled by online technology. Authors from the four corners of the eWorld weigh in with discussions of where the Internet is taking us as an experiential and cultural milieu of modern life. The directions for research provided by this extraordinary overview of an emerging field of inquiry are innovative, visionary and dramatic.

We hope you like it. We hope you'll send us work equally as innovative. We hope you'll tell your friends around the world about how easy it is to access ACM Data Base with our online portal and review system, as well, located at http://www.editorialmanager.com/sigmisdb.
From the chair
Authors: Sipior Janice C. , Lending Diane , Amoroso Donald L. , Shayo Conrad , Vowels Susan A.
Published: November 2007

A warm invitation to attend... "
The Seventh Annual ACM-SIGMIS Reception
," will be held as an ACM-SIGMIS event prior to the International Conference on Information Systems (ICIS2007) in Montréal, Québec, Canada, December 9 -- 12, 2007. Light refreshments will be served.

Where: International Conference on Information Systems (ICIS2007) Montréal, Québec, Canada Fairmont Queen Elizabeth Hotel Room not yet assigned

When: Saturday, December 9, 2007, 5:30 to 7:00 pm

Who: All ACM-SIGMIS members and their invited guests are welcome

.

Please plan to attend the SIGMIS CPR'08 Conference to be held April 3--5, 2008 at the Omni Charlottesville Hotel in Charlottesville, Virginia, USA. The theme of this year's conference is "Refilling the Pipeline: Meeting the Renewed Demand for Information Technology Workers." Additionally, the 2008 conference will include a doctoral student consortium on April 3, 2007 that will host a competition for best doctoral consortium paper. More information can be found at: http://www.sigmis.org/Call_for_Papers_2008.pd.

Please consider volunteering to serve on the Program Committee for the 2008 conference. Members of the Program Committee serve as reviewers and assist in identifying session chairs and discussants. If you would like to serve on the Program Committee, please contact Program Co-Chair Deb Armstrong at djarmstrong@fsu.edu. Let's make the SIGMIS CPR Conference a continuing success!

Also, please continue to consider
Data Base
as an outlet for your research. The new online submission system is available at the Data Base website at: http://the-database.org.
vCRM
Authors: Goel Lakshmi , Mousavidin Elham
Published: November 2007

Virtual worlds provide companies opportunities for valuable co-creation and co-production with their customers. In order to harness this potential, companies need to design effective entry strategies for virtual customer relationship management or vCRM. Understanding how self-expression and collaboration work in virtual worlds can help design better customer-facing strategies. In this paper, we provide a roadmap for companies that want to leverage virtual worlds for vCRM.
Marketing strategies in virtual worlds
Authors: Lui Tsz-Wai , Piccoli Gabriele , Ives Blake
Published: November 2007

More and more businesses are selling products and providing services through multiple channels. 3D virtual worlds are emerging to be one of the channels for companies to communicate with their customers. Being able to simulate similar experiences as customers have in real stores, virtual worlds are able to enhance product knowledge, attitude and purchase intention of customers. However, not all product attributes are able to be experienced virtually because not all kinds of senses (e.g. taste) can be digitzed and presented through a virtual reality interface. Applying theory of cognitive fit and media richness theory, we propose the products attributes that can be experienced virtually with the current technologies. These product attributes and their moderating effects on the relationships between virtual reality and product knowledge, attitude and purchase intention should be studied further so that companies can make decides on the investment in their presence in virtual worlds and the marketing strategies most appropriate for their products.
User acceptance of virtual worlds
Authors: Holsapple Clyde W. , Wu Jiming
Published: November 2007

Research on information technology (IT) adoption focuses almost entirely on productivity-oriented IT such as word processing. Little attention has been directed at investigating adoption of entertainment-oriented IT such as virtual worlds. Contending that it is important to better understand adoption of this technology, we develop a theoretical framework that recognizes the potential of imaginal and emotional responses in explaining user acceptance of virtual worlds. With its basis in the hedonic theory, the research framework may benefit the developers and sponsors of virtual worlds as they strive to build and sustain a customer base. The paper also outlines an example to illustrate one way to approach a consideration of the imaginal and emotional variables.
Islamic perspective
Authors: Yusof Shafiz Affendi Mohd , Zakaria Norhayati
Published: November 2007

Although the number of virtual worlds and their participants is growing rapidly, this phenomena is primarily a Western Culture dominated environment. There is little if any attention paid to other cultures. This article examines this issue from an Islamic perspective? It examines the assumption that if virtual worlds are to become a truly global platform for collaboration, particularly in multinational enterprises, then it will be essential to "encode" the flexibility for social interactions to take place in a way that is sensitive to other cultures.
Virtual worlds
Authors: Cajvaneanu Doina
Published: November 2007

This article raises the question of political innovation that can potentially emerge within, and spread from, the virtual worlds. Locating the signs of political change in the surfacing of innovative political concepts, the article proposes the investigation of keywords in the codes and rules of the virtual communities, as well as the compilation of a glossary of such keywords, as a way to map and analyze the conceptual and political innovation of the latest political incubator.
The dismal economics of virtual worlds
Authors: Noam Eli M.
Published: November 2007

This article analyzes the economics of virtual worlds in order to assess their viability. It identifies eight basic business models. Most of those will not be profitable in a competitive and open general virtual world. However, the owner/operator of the virtual world can capitalize on the value of the community, and benefit from managing and reducing competition. The fundamental economics of digital activities suggest that this sector--and Web 2.0 activities more generally--will be subject to boom-bust cycles.
Federal aviation administration and ada
Authors: O'Leary Jeff
Published: November 2007

The US Federal Aviation Administration (FAA) depends upon large, complex and highly available software systems to manage the vast commercial and civil aviation network and to carry out the agency's mission of ensuring high capacity, efficient and extremely safe air travel for the flying public. The FAA's Tower domain provides air traffic control services in the airport environment. There are more than 500 FAA managed Towers. The Terminal Radar Approach Control (TRACON) domain provides air traffic control services in the terminal environment where aircraft are climbing or descending. There are 197 TRACONs. The En Route domain provides air traffic control services typically above 10,000 feet between departure and arrival domains where aircraft achieve their optimal cruise altitude. There are only 21 En Route centers, so each must provide coverage to very large areas.

Ada has become a strategic technology in developing and sustaining systems that require high availability and high reliability. The FAA Air Traffic Organization's (ATO) major recent initiative, the En-Route Automation Modernization (ERAM) program goes a long way to reintegrating many disparate system components into a modern composite architecture. This program leverages and significantly expands upon previous Ada based systems, so the FAA has a vital interest in Ada language technology now and for the foreseeable future.

Mr. O'Leary will present a federal customer's perspective on systems development and quality, with emphasis on higher reliability, security, and safety. Ada is exceptionally well positioned to support these characteristics, and that is why many current large FAA ATC systems are largely or significantly Ada based. He will touch on past Ada based systems that FAA fielded, the current major ERAM effort, and also where FAA is going in the future with the Next Generation Air Transportation System (NextGen). He will give some insights on what the language and development technologies can contribute towards facilitating the vision of our future.

FAA accepts use of DO-278 as a means of assuring systems integrity for Communications, Navigation, Surveillance, and Air Traffic Management (CNS/ATM) software. Ada has also performed well in DO-278.
Timing neural networks in C and ada
Authors: Carlisle Martin C. , Baird III Leemon C.
Published: November 2007

In this paper, we describe a neural network program that was originally developed in C, then ported to Ada 2005. We explain several simple modifications to the Ada code that reduce the overhead from 76% to 0%. These modifications could provide significant performance gains to other applications, allowing them to combine the safety of Ada with the speed of C. such a complicated data structure. In Section 3, we explain how we modified the code in translating it to Ada. Section 4 describes how we made simple changes to the Ada implementation to eliminate the additional overhead. Section 5 provides conclusions and insights for future projects.
Multi-core + multi-tasking = multi-opportunity?
Authors: Nyberg Karl
Published: November 2007

In this paper we look at the opportunity provided by the introduction of multicore chips to leveraging Ada's multitasking capabilities, with an eye to expanding the influence of Ada in this environment. The Sun Microsystems Sun Fire T1000 running Solaris is used as a platform for investigation of Ada in a multicore environment. Some sample applications are described and evaluated. Guidance on developing multi-tasking applications is also given. Opportunities for the Ada community to leverage this hardware shift to expand Ada's scope of application are presented.
Correctness by construction
Authors: Chapman Rod
Published: November 2007

This presentation will look at the many problems of designing and building high-integrity software and the processes, languages and tools that are currently used. The need to "engineer" our software implies that discipline and reasoning are required, yet most processes and languages seem to obstruct rather than assist such attempts. To help understand why, we consider the history of programming language design, and how this has shaped the way we think about software and constrained our ability to engineer it. In this generally gloomy picture some good news can be found: the emergence of design-by-contract facilities in languages such as Eiffel and SPARK has made a strong impact in some niche areas. In those areas, we have made a rather unusual observation: customers (some having "flirted" with this week's fashionable approach) are "coming back to Ada", recognizing the language's strengths, particularly for high-integrity applications. The presentation will close by considering why Praxis still uses (and chooses) Ada, and the role that Ada has to play in the future of high-integrity software.
Functional, structural, and chemical changes in myosin associated with hydrogen peroxide treatment of skeletal muscle fibers
Authors: Prochniewicz Ewa , Lowe Dawn A. , Spakowicz Daniel J. , Higgins LeeAnn , O'Conor Kate , Thompson LaDora V. , Ferrington Deborah A. , Thomas David D.
Published: November 2007

To understand the molecular mechanism of oxidation-induced inhibition of muscle contractility, we have studied the effects of hydrogen peroxide on permeabilized rabbit psoas muscle fibers, focusing on changes in myosin purified from these fibers. Oxidation by 5 mM peroxide decreased fiber contractility (isometric force and shortening velocity) without significant changes in the enzymatic activity of myofibrils and isolated myosin. The inhibitory effects were reversed by treating fibers with dithiothreitol. Oxidation by 50 mM peroxide had a more pronounced and irreversible inhibitory effect on fiber contractility and also affected enzymatic activity of myofibrils, myosin, and actomyosin. Peroxide treatment also affected regulation of contractility, resulting in fiber activation in the absence of calcium. Electron paramagnetic resonance of spin-labeled myosin in muscle fibers showed that oxidation increased the fraction of myosin heads in the strong-binding structural state under relaxing conditions (low calcium) but had no effect under activating conditions (high calcium). This change in the distribution of structural states of myosin provides a plausible explanation for the observed changes in both contractile and regulatory functions. Mass spectroscopy analysis showed that 50 mM but not 5 mM peroxide induced oxidative modifications in both isoforms of the essential light chains and in the heavy chain of myosin subfragment 1 by targeting multiple methionine residues. We conclude that 1) inhibition of muscle fiber contractility via oxidation of myosin occurs at high but not low concentrations of peroxide and 2) the inhibitory effects of oxidation suggest a critical and previously unknown role of methionines in myosin function.
Neural agrin controls maturation of the excitation-contraction coupling mechanism in human myotubes developing in vitro
Authors: Bandi Elena , Jevšek Marko , Mars Tomaz , Jurdana Mihaela , Formaggio Elena , Sciancalepore Marina , Fumagalli Guido , Grubič Zoran , Ruzzier Fabio , Lorenzon Paola
Published: November 2007

The aim of this study was to elucidate the mechanisms responsible for the effects of innervation on the maturation of excitation-contraction coupling apparatus in human skeletal muscle. For this purpose, we compared the establishment of the excitation-contraction coupling mechanism in myotubes differentiated in four different experimental paradigms: 1) aneurally cultured, 2) cocultured with fetal rat spinal cord explants, 3) aneurally cultured in medium conditioned by cocultures, and 4) aneurally cultured in medium supplemented with purified recombinant chick neural agrin. Ca2+ imaging indicated that coculturing human muscle cells with rat spinal cord explants increased the fraction of cells showing a functional excitation-contraction coupling mechanism. The effect of spinal cord explants was mimicked by treatment with medium conditioned by cocultures or by addition of 1 nM of recombinant neural agrin to the medium. The treatment with neural agrin increased the number of human muscle cells in which functional ryanodine receptors (RyRs) and dihydropyridine-sensitive L-type Ca2+ channels were detectable. Our data are consistent with the hypothesis that agrin, released from neurons, controls the maturation of the excitation-contraction coupling mechanism and that this effect is due to modulation of both RyRs and L-type Ca2+ channels. Thus, a novel role for neural agrin in skeletal muscle maturation is proposed.
AMPK activation with AICAR provokes an acute fall in plasma [K+]
Authors: Zheng Dan , Perianayagam Anjana , Lee Donna H. , Brannan M. Douglas , Yang Li E. , Tellalian David , Chen Pei , Lemieux Kathleen , Marette André , Youn Jang H. , McDonough Alicia A.
Published: November 2007

AMP-activated protein kinase (AMPK), activated by an increase in intracellular AMP-to-ATP ratio, stimulates pathways that can restore ATP levels. We tested the hypothesis that AMPK activation influences extracellular fluid (ECF) K+ homeostasis. In conscious rats, AMPK was activated with 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) infusion: 38.4 mg/kg bolus then 4 mg·kg−1·min−1 infusion. Plasma [K+] and [glucose] both dropped at 1 h of AICAR infusion and [K+] dropped to 3.3 ± 0.04 mM by 3 h, linearly related to the increase in muscle AMPK phosphorylation. AICAR treatment did not increase urinary K+ excretion. AICAR lowered [K+] whether plasma [K+] was chronically elevated or lowered. The K+ infusion rate needed to maintain baseline plasma [K+] reached 15.7 ± 1.3 μmol K+·kg−1·min−1 between 120 and 180 min AICAR infusion. In mice expressing a dominant inhibitory form of AMPK in the muscle (Tg-KD1), baseline [K+] was not different from controls (4.2 ± 0.1 mM), but the fall in plasma [K+] in response to AICAR (0.25 g/kg) was blunted: [K+] fell to 3.6 ± 0.1 in controls and to 3.9 ± 0.1 mM in Tg-KD1, suggesting that ECF K+ redistributes, at least in part, to muscle ICF. In summary, these findings illustrate that activation of AMPK activity with AICAR provokes a significant fall in plasma [K+] and suggest a novel mechanism for redistributing K+ from ECF to ICF.
Apical membrane targeting and trafficking of the human proton-coupled transporter in polarized epithelia
Authors: Subramanian Veedamali S. , Marchant Jonathan S. , Said Hamid M.
Published: November 2007

The human proton-coupled folate transporter (hPCFT) is a recently discovered intestinal transporter involved in folate uptake in epithelia (and possibly other cells). Little is currently known about the structure-function relationship of the different domains of this transporter, particularly which regions are important for substrate transport as well as targeting of the transporter to the apical cell surface of polarized cells. Here we have investigated the role of the COOH-terminal domain and a well-conserved sequence separating transmembrane (TM) domains TM2 and TM3 (DXXGRR; amino acids 109–114) speculated by others to be important for transport function. Using live cell imaging approaches, we show that 1) an hPCFT-yellow fluorescent protein construct is functionally expressed at the apical membrane domain and is localized differentially to the human reduced folate carrier; 2) the predicted cytoplasmic COOH-terminal region of hPCFT is not essential for apical targeting or transporter functionality; 3) mutations that ablate a consensus β-turn sequence separating predicted TM2 and TM3 abolished apical [3H]folic acid uptake as a consequence of endoplasmic reticulum retention of mutant, likely misfolded, transporters; and 4) cell surface delivery of hPCFT is disrupted by microtubule depolymerization or by overexpression of the dynactin complex dynamitin (p50). For the first time, our data present information regarding structure-function and membrane targeting of the hPCFT polypeptide, as well as the mechanisms that control its steady-state expression in polarized cells.
Insulin promotes glycogen synthesis in the absence of GSK3 phosphorylation in skeletal muscle
Authors: Bouskila Michale , Hirshman Michael F. , Jensen Jørgen , Goodyear Laurie J. , Sakamoto Kei
Published: November 2007

Insulin promotes dephosphorylation and activation of glycogen synthase (GS) by inactivating glycogen synthase kinase (GSK) 3 through phosphorylation. Insulin also promotes glucose uptake and glucose 6-phosphate (G-6- P) production, which allosterically activates GS. The relative importance of these two regulatory mechanisms in the activation of GS in vivo is unknown. The aim of this study was to investigate if dephosphorylation of GS mediated via GSK3 is required for normal glycogen synthesis in skeletal muscle with insulin. We employed GSK3 knockin mice in which wild-type GSK3α and -β genes are replaced with mutant forms (GSK3α/βS21A/S21A/S9A/S9A), which are nonresponsive to insulin. Although insulin failed to promote dephosphorylation and activation of GS in GSK3α/βS21A/S21A/S9A/S9Amice, glycogen content in different muscles from these mice was similar compared with wild-type mice. Basal and epinephrine-stimulated activity of muscle glycogen phosphorylase was comparable between wild-type and GSK3 knockin mice. Incubation of isolated soleus muscle in Krebs buffer containing 5.5 mM glucose in the presence or absence of insulin revealed that the levels of G-6- P, the rate of [14C]glucose incorporation into glycogen, and an increase in total glycogen content were similar between wild-type and GSK3 knockin mice. Injection of glucose containing 2-deoxy-[3H]glucose and [14C]glucose also resulted in similar rates of muscle glucose uptake and glycogen synthesis in vivo between wild-type and GSK3 knockin mice. These results suggest that insulin-mediated inhibition of GSK3 is not a rate-limiting step in muscle glycogen synthesis in mice. This suggests that allosteric regulation of GS by G-6- P may play a key role in insulin-stimulated muscle glycogen synthesis in vivo.
Determinants of intramyocellular triglyceride turnover: implications for insulin sensitivity
Authors: Moro Cédric , Bajpeyi Sudip , Smith Steven R.
Published: November 2007

Increased intramyocellular triglyceride (IMTG) content is found in both insulin-sensitive endurance-trained subjects and insulin-resistant obese/type 2 diabetic subjects. A high turnover rate of the IMTG pool in athletes is proposed to reduce accumulation of lipotoxic intermediates interfering with insulin signaling. IMTG turnover is a composite measure of the dynamic balance between lipolysis and lipid synthesis; both are influenced by mitochondrial fat oxidation and plasma free fatty acid availability. Therefore, more attention should be given to the factors controlling the rate of turnover of IMTG. In this review, particular attention has been given to muscle oxidative capacity, plasma free fatty acid availability, and IMTG hydrolysis (lipolysis) and synthesis. A higher oxidative, lipolytic, and lipid storage capacity in the muscle of endurance-trained subjects reflects a higher fractional turnover of the IMTG pool. Thus the co-localization of intermyofibrillar lipid droplets and mitochondria allows for a fine coupling of lipolysis of the IMTG pool to mitochondrial β-oxidation. Conversely, reduced oxidative capacity and a mismatch between IMTG lipolysis and β-oxidation might be detrimental to insulin sensitivity by generating several lipotoxic intermediates in sedentary populations including obese/type 2 diabetic subjects. Further studies are clearly required to better understand the relationship between the rate of turnover of IMTG and the accumulation of lipotoxic intermediates in the pathophysiology of insulin resistance.
Protection of transplant-induced hepatic ischemia/reperfusion injury with carbon monoxide via MEK/ERK1/2 pathway downregulation
Authors: Kaizu Takashi , Ikeda Atsushi , Nakao Atsunori , Tsung Allan , Toyokawa Hideyoshi , Ueki Shinya , Geller David A. , Murase Noriko
Published: November 2007

Carbon monoxide (CO), a product of heme degradation by heme oxygenases (HO), has been shown to provide cytoprotection in various tissue injury models. This study examined the efficacy and molecular mechanisms of exogenously delivered inhaled CO in protecting liver grafts from cold ischemia/reperfusion (I/R) injury associated with liver transplantation. Orthotopic syngenic liver transplantation (OLT) was performed in Lewis rats with 18-h cold preservation in University of Wisconsin solution. Recipients were exposed to air or different concentrations of CO (20–250 ppm) for 1 h before and 24 h after OLT and killed 1–48 h posttransplant. CO inhalation significantly decreased serum alanine transaminase (ALT) levels and suppressed hepatic necrosis and neutrophil accumulation at 24–48 h after OLT in a dose-dependent manner. Reduced hepatic injury with inhaled CO is associated with marked downregulation of early mRNA expression for TNF-α and IL-6. Expression in liver grafts of mRNA and protein of the stress-responding enzyme inducible nitric oxide synthase was significantly reduced by CO, while HO-1 was only marginally suppressed. Cold hepatic I/R injury was associated with prompt MAPK phosphorylation in liver grafts at 1 h after OLT, and CO significantly inhibited phosphorylation of ERK1/2 MAPK and its upstream MEK1/2 and downstream transcriptional factor c-Myc. CO also significantly inhibited I/R injury-induced STAT1 and STAT3 activation. In contrast, CO did not inhibit p38 or JNK MAPK pathways during hepatic I/R injury. Results demonstrate that exogenous CO suppresses early proinflammatory and stress-response gene expression and efficiently ameliorates hepatic I/R injury. The possible mechanism may include the downregulation of MEK/ERK1/2 signaling pathway with CO.
Exercise accelerates cutaneous wound healing and decreases wound inflammation in aged mice
Authors: Keylock K. Todd , Vieira Victoria J. , Wallig Matthew A. , DiPietro Luisa A. , Schrementi Megan , Woods Jeffrey A.
Published: November 2007

The purpose of this study was to determine the effect of exercise on wound healing and inflammation in young (3 mo) and old (18 mo) female BALB/cByJ mice. Mice were assigned to either exercise or sedentary control (control) groups. The exercise group mice were run on a motorized treadmill at a moderate intensity 30 min/day for 8 days. All mice were given four full-thickness dermal wounds, and the rate of wound closure was assessed daily for 10 days. Four months later, the aged mice were rerandomized to treatment, wounded again in different locations, and wounds were harvested at 1, 3, or 5 days postwounding. Wound tissue was analyzed for IL-1β, IL-6, keratinocyte chemoattractant (KC), monocyte chemoattractant protein-1 (MCP-1), and TNF-α protein. Myeloperoxidase (MPO) activity and F4/80 mRNA were assessed as an indirect measure of neutrophil and macrophage content, respectively. There was a trend ( P = 0.10) for exercise to reduce wound size in young mice, and exercise significantly ( P < 0.05) decreased wound size in old mice. TNF-α, KC, and MCP-1 were significantly ( P < 0.05) lower in wounds from exercised old mice compared with control. No group differences were found for wound IL-1β or IL-6, MPO activity, or F4/80 mRNA. Our data suggest that exercise accelerates the wound healing process in old mice. This improved healing response in the old mice may be the result of an exercise-induced anti-inflammatory response in the wound.
Fat pad-specific effects of lipectomy on foraging, food hoarding, and food intake
Authors: Dailey Megan E. , Bartness Timothy J.
Published: November 2007

Unlike most species, after food deprivation, Siberian hamsters increase foraging and food hoarding, two appetitive ingestive behaviors, but not food intake, a consummatory ingestive behavior. We previously demonstrated (Wood AD, Bartness TJ, Am J Physiol Regul Integr Comp Physiol 272: R783−R792, 1997) that increases in food hoarding are triggered by directly decreasing body fat levels through partial surgical lipectomy; however, we did not test if lipectomy affected foraging, nor if the magnitude of the lipid deficit affected food hoard size. Therefore, we tested whether varying the size of the lipectomy-induced lipid deficit and/or foraging effort affected foraging, food hoarding, or food intake. This was accomplished by housing adult male Siberian hamsters in a foraging/hoarding system and removing (x) both epididymal white adipose tissue (EWATx) pads, both inguinal white adipose tissue (IWATx) pads, or both EWAT and IWAT pads (EWATx + IWATx) and measuring foraging, food hoarding, and food intake for 12 wk. The lipectomy-induced lipid deficit triggered different patterns of white adipose tissue mass compensation that varied with foraging effort. Foraging for food (10 wheel revolutions to earn a food pellet) abolished the EWATx-induced compensation in IWAT pad mass. The magnitude of the lipid deficit did not engender a proportional change in any of the appetitive or consummatory ingestive behaviors. EWATx caused the greatest increase in food hoarding compared with IWATx or EWATx + IWATx, when animals were required to forage for their food. Collectively, it appears that the magnitude of a lipid deficit does not affect appetitive or consummatory behaviors; rather, when energy (foraging) demands are increased, loss of specific (gonadal) fat pads can preferentially stimulate increases in food hoarding.
A high-fat diet raises fasting plasma CCK but does not affect upper gut motility, PYY, and ghrelin, or energy intake during CCK-8 infusion in lean men
Authors: Little Tanya J. , Feltrin Kate L. , Horowitz Michael , Meyer James H. , Wishart Judith , Chapman Ian M. , Feinle-Bisset Christine
Published: November 2007

There is evidence from studies in animals that the effects of both fat and CCK on gastrointestinal function and energy intake are attenuated by consumption of a high-fat diet. In humans, the effects of exogenous CCK-8 on antropyloroduodenal motility, plasma CCK, peptide YY (PYY), and ghrelin concentrations, appetite, and energy intake are attenuated by a high-fat diet. Ten healthy lean males consumed isocaloric diets (∼15,400 kJ per day), containing either 44% (high-fat, HF) or 9% (low-fat, LF) fat, for 21 days in single-blind, randomized, cross-over fashion. Immediately following each diet (i.e., on day 22), subjects received a 45-min intravenous infusion of CCK-8 (2 ng·kg−1·min−1), and effects on antropyloroduodenal motility, plasma CCK, PYY, ghrelin concentrations, hunger, and fullness were determined. Thirty minutes after commencement of the infusion, subjects were offered a buffet-style meal, from which energy intake (in kilojoules) was quantified. Body weight was unaffected by the diets. Fasting CCK ( P < 0.05), but not PYY and ghrelin, concentrations were greater following the HF, compared with the LF, diet. Infusion of CCK-8 stimulated pyloric pressures ( P < 0.01) and suppressed antral and duodenal pressures ( P < 0.05), with no difference between the diets. Energy intake also did not differ between the diets. Short-term consumption of a HF diet increases fasting plasma CCK concentrations but does not affect upper gut motility, PYY and ghrelin, or energy intake during CCK-8 infusion, in a dose of 2 ng·kg−1·min−1, in healthy males.
Detectable serum flagellin and lipopolysaccharide and upregulated anti-flagellin and lipopolysaccharide immunoglobulins in human short bowel syndrome
Authors: Ziegler Thomas R. , Luo Menghua , Estívariz Concepción F. , Moore Daniel A. , Sitaraman Shanthi V. , Hao Li , Bazargan Niloofar , Klapproth Jan-Michael , Tian Junqiang , Galloway John R. , Leader Lorraine M. , Jones Dean P. , Gewirtz Andrew T.
Published: November 2007

Gut barrier dysfunction may occur in short bowel syndrome (SBS). We hypothesized that systemic exposure to flagellin and lipopolysaccharide (LPS) in SBS might regulate specific immune responses. We analyzed serial serum samples obtained from parenteral nutrition (PN)-dependent patients with SBS versus non-SBS control serum. Serum from 23 adult SBS patients was obtained at baseline and 4, 8, 12, 16, 20, and 24 wk in a trial of modified diet with or without growth hormone. Control serum was obtained from 48 healthy adults and 37 adults requiring PN during critical illness. Serum flagellin was detected by an ELISA recognizing an array of gram-negative flagellins, and LPS was detected by limulus assay. Serum flagellin- and LPS-specific immunoglobulin levels (IgM, IgA, and IgG) were determined by ELISA. Serum flagellin and LPS were undetectable in control subjects. In contrast, serum flagellin, LPS, or both were detected in 14 SBS patients (61%) during one or more time points [flagellin alone, 5/23 (22%); LPS alone, 6/23 (26%); or flagellin + LPS, 3/23 (13%)]. Flagellin-specific serum IgM, IgA, and IgG levels were markedly increased in SBS patients compared with both control populations and remained elevated during the 6-mo study period. LPS-specific IgA was significantly higher in SBS patients compared with healthy controls; LPS-specific IgM, IgA, and IgG levels each decreased over time in association with PN weaning. We conclude that adults with PN-dependent SBS are systemically exposed to flagellin and LPS, presumably from the gut lumen. This likely regulates innate and adaptive immune responses to these specific bacterial products.
Left ventricular dysfunction and associated cellular injury in rats exposed to chronic intermittent hypoxia
Authors: Chen Ling , Zhang Jin , Gan Tracey X. , Chen-Izu Ye , Hasday Jeffrey D. , Karmazyn Morris , Balke C. William , Scharf Steven M.
Published: November 2007

Obstructive sleep apnea (OSA) increases cardiovascular morbidity and mortality. We have reported that chronic intermittent hypoxia (CIH), a direct consequence during OSA, leads to left ventricular (LV) remodeling and dysfunction in rats. The present study is to determine LV myocardial cellular injury that is possibly associated with LV global dysfunction. Fifty-six rats were exposed either to CIH (nadir O2 4–5%) or sham (handled normoxic controls, HC), 8 h/day for 6 wk. At the end of the exposure, we studied LV global function by cardiac catheterization, and LV myocardial cellular injury by in vitro analyses. Compared with HC, CIH animals demonstrated elevations in mean arterial pressure and LV end-diastolic pressure, but reductions in cardiac output (CIH 141.3 ± 33.1 vs. HC 184.4 ± 21.2 ml·min−1·kg−1, P < 0.01), maximal rate of LV pressure rise in systole (+dP/d t), and maximal rate of LV pressure fall in diastole (−dP/d t). CIH led to significant cell injury in the left myocardium, including elevated LV myocyte size, measured by cell surface area (CIH 3,564 ± 354 vs. HC 2,628 ± 242 μm2, P < 0.05) and cell length (CIH 148 ± 23 vs. HC 115 ± 16 μm, P < 0.05), elevated terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-stained positive cell number (CIH 98 ± 45 vs. HC 15 ± 13, P < 0.01), elevated caspase-3 activity (906 ± 249 vs. 2,275 ± 1,169 pmol·min−1·mg−1, P < 0.05), and elevated expression of several remodeling gene markers, including c-fos, atrial natriuretic peptide, β-myosin heavy chain, and myosin light chain-2. However, there was no difference between groups in sarcomere contractility of isolated LV myocytes, or in LV collagen deposition on trichrome-stained slices. In conclusion, CIH-mediated LV global dysfunction is associated with myocyte hypertrophy and apoptosis at the cellular level.
Functional Parameters of Voltage-Activated Ca2+Currents From Olfactory Interneurons in the Antennal Lobe ofPeriplaneta americana
Authors: Husch Andreas , Hess Simon , Kloppenburg Peter
Published: November 2007

Toward our goal to better understand the physiological parameters that mediate olfactory information processing on the cellular level, voltage-activated calcium currents ( ICa) in olfactory interneurons of the antennal lobe from adult cockroaches were analyzed under two conditions: 1) in acutely dissociated cells (in vitro) and 2) in an intact brain preparation (in situ). The study included an analysis of modulatory effects of potential inorganic and organic Ca2+channel blockers. ICawas isolated and identified using pharmacological, voltage, and ion substitution protocols. ICaconsisted of two components: transient and sustained. The decay of the transient component was largely Ca2+dependent. In vitro, ICahad an activation threshold of −50 mV with a maximal peak current at −7 mV and a half-maximal voltage ( V0.5act) for tail-current activation of −18 mV. In situ these parameters were significantly shifted to more depolarized membrane potentials: ICaactivated at −40 mV with a maximal peak current at 8 mV and a V0.5actfor tail-current activation of −11 mV. The sensitivity of ICato the divalent cations Cd2+, Co2+, and Ni2+was dose dependent. The most effective blocker was Cd2+with an IC50of 10−5M followed by Ni2+(IC50= 3.13 × 10−3M) and Co2+(IC50= 1.06 × 10−3M). The organic channel blockers verapamil, diltiazem, and nifedipine also blocked ICain a dose-dependent way and had differential effects on the current waveform. Verapamil blocked ICawith an IC50of 1.5 × 10−4M and diltiazem had an IC50of 2.87 × 10−4M. Nifedipine blocked ICaby 33% at a concentration of 10−4M.
Can Observational Training Substitute Motor Training in Preventing Backward Balance Loss After an Unexpected Slip During Walking?
Authors: Bhatt T. , Pai Y.-C.
Published: November 2007

A person's awareness of potential slippery walking conditions induces a cautious gait pattern. The purposes of this study were to determine whether neuromechanical changes associated with such cognitive conditioning are sufficient to alter the outcome of a slip and whether the effects of such conditioning are comparable to those of motor training. Prior to their own first slip exposure, 18 young subjects watched videos and slides demonstrating where and how the slip would occur and how people adapted to repeated-slip exposure (observe). The outcomes of the first slip exposure experienced by another 16 subjects who did not receive any such information were used as controls (naïve). The latter subjects subsequently experienced an additional 23 slips and thus served in a dual-role as the motor training group (motor). Gait stability as measured against backward loss of balance (BLOB) was obtained for pre- and postslip instances. A protective step landing posterior to the slipping-limb identified each BLOB outcome. The observe group had a greater postslip stability and lower slip displacement and velocity than the naïve group. However, such effects were insufficient to prevent balance loss (100% BLOB). The motor group showed significantly better performance on the last training slip (0% BLOB) than did the observe group. The results indicated that updating the cognitive centers of the CNS with awareness and perceptual knowledge through observational training can yield tangible benefits. Nonetheless observation could not replace the task-specific motor training that adaptively updated the internal representations of stability limits for prevention of BLOB.
Modifications of Locomotor Pattern Underlying Escape Behavior in the Lamprey
Authors: Islam Salma S. , Zelenin Pavel V.
Published: November 2007

Two forms of undulatory locomotion in the lamprey (a lower vertebrate) have been described earlier: fast forward swimming (FFS) used for long distance migrations and slow backward swimming (SBS) used for escape from adverse tactile stimuli. In the present study, we describe another form of escape behavior: slow forward swimming (SFS). We characterize the kinematic and electromyographic patterns of SFS and compare them with SBS and FFS. The most striking feature of SFS is nonuniformity of shape and speed of the locomotor waves propagating along the body: close to the site of stimulation, the waves slow down and the body curvature increases several-fold due to enhanced muscle activity. Lesions of afferents showed that sensory information critical for elicitation of SFS is transmitted through the dorsal roots. In contrast, sensory signals that induce SBS are transmitted through the dorsal roots, lateral line nerves, and trigeminal nerves. Persistence of SFS and SBS after different lesions of the spinal cord suggests that the ascending and descending pathways, necessary for induction of SBS and SFS, are dispersed over the cross section of the spinal cord. As shown previously, during FFS (but not SBS) the lamprey maintains the dorsal-side-up body orientation due to vestibular postural reflexes. In this study we have found that the orientation control is absent during SFS. The role of the spinal cord and the brain stem in generation of different forms of undulatory locomotion is discussed.