bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of navigability of Web applications for improving blind usability
Authors: Takagi Hironobu , Saito Shin , Fukuda Kentarou , Asakawa Chieko
Published: September 2007

Various accessibility activities are improving blind access to the increasingly indispensable WWW. These approaches use various metrics to measure the Web's accessibility. “Ease of navigation” (navigability) is one of the crucial factors for blind usability, especially for complicated webpages used in portals and online shopping sites. However, it is difficult for automatic checking tools to evaluate the navigation capabilities even for a single webpage. Navigability issues for complete Web applications are still far beyond their capabilities.

This study aims at obtaining quantitative results about the current accessibility status of real world Web applications, and analyzes real users' behavior on such websites. In Study 1, an automatic analysis method for webpage navigability is introduced, and then a broad survey using this method for 30 international online shopping sites is described. The next study (Study 2) focuses on a fine-grained analysis of real users' behavior on some of these online shopping sites. We modified a voice browser to record each user's actions and the information presented to that user. We conducted user testing on existing sites with this tool. We also developed an analysis and visualization method for the recorded information. The results showed us that users strongly depend on scanning navigation instead of logical navigation. A landmark-oriented navigation model was proposed based on the results. Finally, we discuss future possibilities for improving navigability, including proposals for voice browsers.
Evaluating DANTE
Authors: Yesilada Yeliz , Stevens Robert , Harper Simon , Goble Carole
Published: September 2007

The importance of the World Wide Web for information dissemination is indisputable. However, the dominance of visual design on the Web leaves visually disabled people at a disadvantage. Although assistive technologies, such as screen readers, usually provide basic access to information, the richness of the Web experience is still often lost. In particular, traversing the Web becomes a complicated task since the richness of visual objects presented to their sighted counterparts are neither appropriate nor accessible to visually disabled users. To address this problem, we have proposed an approach called Dante in which Web pages are annotated with semantic information to make their traversal properties explicit. Dante supports usage of different annotation techniques and as a proof-of-concept in this article, pages are annotated manually which when transcoded become rich. We first introduce Dante and then present a user evaluation which compares how visually disabled users perform certain travel-related tasks on original and transcoded versions of Web pages. We discuss the evaluation methodology in detail and present our findings, which provide useful insights into the transcoding process. Our evaluation shows that, in tests with users, document objects transcoded with Dante have a tendency to be much easier for visually disabled users to interact with when traversing Web pages.
Modeling process-driven and service-oriented architectures using patterns and pattern primitives
Authors: Zdun Uwe , Hentrich Carsten , Dustdar Schahram
Published: September 2007

Service-oriented architectures are increasingly used in the context of business processes. However, the proven practices for process-oriented integration of services are not well documented yet. In addition, modeling approaches for the integration of processes and services are neither mature nor do they exactly reflect the proven practices. In this article, we propose a pattern language for process-oriented integration of services to describe the proven practices. Our main contribution is a modeling concept based on pattern primitives for these patterns. A pattern primitive is a fundamental, precisely specified modeling element that represents a pattern. We present a catalog of pattern primitives that are precisely modeled using OCL constraints and map these primitives to the patterns in the pattern language of process-oriented integration of services. We also present a model validation tool that we have developed to support modeling the process-oriented integration of services, and an industrial case study in which we have applied our results.
A culture of community
Authors: Harper Simon
Published: September 2007

The world increasingly asks 'how do I benefit?' as opposed to 'how can I contribute?'. In an age of consumerism and the 'me' culture how can an ethos of community contribution flourish. As the SIG sees' it's numbers stable but it's student numbers converting to professional memberships decline, how can we stem the tide. It's time to think differently about what it means to be part of the SIGWEB community, we must move away from a culture of benefits to a culture of community. I think this means some pretty serious changes to how we think of ourselves as a community and entails a move to place more emphasis on social capital, the advantage created by a person's location in the relationships of the SIGWEB community. Indeed, for a community originally named 'SIGLINK' these interpersonal relationships seem even more relevant. So how to proceed? Well, I'd like to start a discussion about this topic with all members of the SIG through our 'Google--Group' URL at: http://groups.google.com/group/sigweb-community.
An anomaly in an interpreter using GCC source-code-level register allocation
Authors: Hou Ting-Wei , Chen Fuh-Gwo
Published: September 2007

An anomaly of unexpected performance in an interpreter whose frequently accessed variables are manually assigned to hard registers by GCC source-code-level register allocation is presented. A hard-registered virtual program counter and stack pointer as well as a byte-code translation are experimented on both register-rich PowerPC and register-limited Intel x86. According to the study of the anomaly, a hard register should not be assigned singly to a variable in an interpreter due to higher register pressure.
A programming environment for ubiquitous computing environment
Authors: Oh Minkyoung , Lee Jiyeon , Chang Byeong-Mo , Ahn Joonseon , Doh Kyung-Goo
Published: September 2007

The goal of this research is to provide an advanced programming environment for ubiquitous computing, which facilitates the development of secure and reliable ubiquitous software. A discussion follows on the design and implementation of a ubiquitous programming framework, which is based on high-level policy description language. A context-based access control manager(CACM) was implemented for context-aware access control, while an adaptation engine was integrated for context adaptation in dynamically changing environments. A simulator was also implemented for conducting experiments with this framework for ubiquitous applications.
Raw pointers in application classes of C++ considered harmful
Authors: Smirnov Igor B.
Published: September 2007

In order to achieve good reliability, clarity, scalability and re-usability of the application high-level programs written in C++ the raw pointers should not be used as class members (fields), because the raw pointers are too dangerous in this role and they do not represent meaningful relations between objects. Instead of raw pointers two smart pointers should be used. The first one describes exclusive unique ownership with synchronization of objects copying and deletion. The second one describes inclusive references to independent alien objects with invalidating the reference at the deletion of the addressed object. All power of object-oriented programming is preserved, but difficulties and errors are eliminated.
Meeting in the ether
Authors: Damer Bruce
Published: September 2007

The virtual-world environment of Second Life is attracting considerable media attention. Some see it as heralding new ways of working and playing online; others question its prospects. In this column, Bruce Damer considers the history of virtual worlds, in which he played an active part. Upon meeting Bruce in Prague in 1994, I was immediately impressed with his insight, energy, and creativity. His DigiBarn computer museum in Santa Cruz is a unique, invaluable computer-history resource, including vintage computers that visitors can experience hands-on.---Jonathan Grudin, Timelines editor
SwissCHI's HCI education
Authors: Mueller Lothar
Published: September 2007

A master's in advanced studies of human computer interaction design has been offered in Switzerland since 2006. SwissCHI initiated and defined the program in collaboration with three Swiss universities. Maybe this success story could be an example for other local SIGCHI chapters.
Poor man's broadband
Authors: Saif Umar , Chudhary Ahsan Latif , Butt Shakeel , Butt Nabeel Farooq
Published: September 2007

In this paper we present a peer-to-peer dialup architecture for accelerated "Internet access" in the developing world. Our proposed architecture provides a mechanism for multiplexing the scarce and expensive international Internet bandwidth over higher bandwidth p2p dialup connections within a developing country. Our system combines a number of architectural components, such as incentive-driven p2p data transfer, intelligent connection interleaving and content-prefetching. This paper presents a detailed design, implementation and evaluation of our dialup p2p data transfer architecture inspired by Bittorrent.
A shortest-path-based topology control algorithm in wireless multihop networks
Authors: Shen Yao , Cai Yunze , Xu Xiaoming
Published: September 2007

In this paper, we present a shortest-path-based algorithm, called local shortest path(LSP), for topology control in wireless multihop networks. In this algorithm, each node locally computes the shortest paths connecting itself to nearby nodes based on some link weight function, and then it selects all the second nodes on the shortest paths as its logical neighbors in the final topology. Any energy model can be employed in LSP to design the link weight function whose value represents the power consumption required in the transmission along a link. We analytically prove that such a simple algorithm maintains network connectivity and guarantees that the minimal energy path between any two nodes is preserved in the final topology. Simulation results show that LSP can reduce the energy consumption, especially in heterogenous network.
JumboGen
Authors: Salyers David , Jiang Yingxin , Striegel Aaron , Poellabauer Christian
Published: September 2007

Network line speeds have increased at a significant rate. Unfortunately, network performance has not been able to keep pace with increases in line speed. This is due to the majority of packets being less than or equal to 100 bytes in addition to network routers not being able to scale well with the increased number of packets. In this paper we present our solution, JumboGen, an approach that will allow for a higher utilization of larger packet sizes on a domain-wise basis. Through simulations and experimentation, we show that the dynamic creation of jumbo packets decreases the number of packets processed by core routers and does not have an adverse impact on link utilization or fairness. The final result of JumboGen is a reduction in the number of packets seen by core routers which directly improves network scalability.
Exploiting KAD
Authors: Steiner Moritz , En-Najjary Taoufik , Biersack Ernst W.
Published: September 2007

Peer-to-peer systems have seen a tremendous growth in the last few years and peer-to-peer traffic makes a major fraction of the total traffic seen in the Internet. The dominating application for peer-to-peer is file sharing. Some of the most popular peer-to-peer systems for file sharing have been Napster, FastTrack, BitTorrent, and eDonkey, each one counting a million or more users at their peak time.

We got interested in kad since it is the only DHT that has been part of very popular peer-to-peer system with several million simultaneous users. As we have been studying kad over the course of the last 18 months we have been both, fascinated and frightened by the possibilities kad offers. Mounting a Sybil attack is very easy in kad and allows to compromise the privacy of kad users, to compromise the correct operation of the key lookup and to mount DDOS with very little resources.

In this paper, we will relate some of our findings and point out how kad can be used and misused.
You must be joking...
Authors: Faloutsos Michalis
Published: September 2007

Humor is something that I take very seriously. Recently, I have been thinking a lot about it. It all started with a pet peeve of mine that got spurred on by a comment from a student. Then, I started writing and it came out completely different from what I expected. It could be mean or pointless. Or it could be both, you be the judge.
Towards an active network architecture
Authors: Tennenhouse David L. , Wetherall David J.
Published: September 2007

Active networks allow their users to inject customized programs into the nodes of the network. An extreme case, in which we are most interested, replaces packets with "capsules" -- program fragments that are executed at each network router/switch they traverse.

Active architectures permit a massive increase in the sophistication of the computation that is performed within the network. They will enable new applications, especially those based on application-specific multicast, information fusion, and other services that leverage network-based computation and storage. Furthermore, they will accelerate the pace of innovation by decoupling network services from the underlying hardware and allowing new services to be loaded into the infrastructure on demand.

In this paper, we describe our vision of an active network architecture, outline our approach to its design, and survey the technologies that can be brought to bear on its implementation. We propose that the research community mount a joint effort to develop and deploy a wide area ActiveNet.
Very low-cost internet access using KioskNet
Authors: Guo S. , Falaki M. H. , Oliver E. A. , Ur Rahman S. , Seth A. , Zaharia M. A. , Keshav S.
Published: September 2007

Rural Internet kiosks in developing regions can cost-effectively provide communication and e-governance services to the poorest sections of society. A variety of technical and non-technical issues have caused most kiosk deployments to be economically unsustainable [1]. KioskNet addresses the key technical problems underlying kiosk failure by using robust 'mechanical backhaul' for connectivity [2], and by using low-cost and reliable kiosk-controllers to support services delivered from one or more recycled PCs. KioskNet also addresses related issues such as security, user management, and log collection. In this paper, we describe the KioskNet system, outlining its hardware, software, and security architecture. We describe a pilot deployment, and how we used lessons from this deployment to re-design our initial proto-type.
[Software patents] The good, the bad, and the messy
Authors: Thatcher Matt E. , Pingry David E.
Published: September 2007

The goal of improving patent quality remains elusive both from an economic and process perspective.
Knowledge services on the semantic web
Authors: Mentzas Gregoris , Kafentzis Kostas , Georgolios Panos
Published: September 2007

Developing infrastructures for trading knowledge services using semantic technologies.
[Getting ideas to market] Current issues faced by technology entrepreneurs
Authors: Umesh U.N. , Jessup Len , Huynh Minh Q.
Published: September 2007

A great idea does not always result in a successful product. Often the winners are the ones to make it over all the hurdles along the way.
Inspiring students to pursue computing degrees
Authors: Akbulut Asli Yagmur , Looney Clayton Arlen
Published: September 2007

Their aspirations are our possibilities.
Physical product reengineering with embedded information technology
Authors: Konana Prabhudev , Ray Gautam
Published: September 2007

Physical products increasingly incorporate an IT component, requiring manufacturers to adapt their production and support processes.
Business process development life cycle methodology
Authors: Papazoglou Michael P. , van den Heuvel Willem-Jan
Published: September 2007

An innovative roadmap brings together the worlds of business processes and Web services, harnessing their power to construct industrial-strength business applications.
Business applications of unstructured text
Authors: Kuechler William L.
Published: September 2007

Crunching unstructured text rather than numbers is the basis for a new class of high-value applications ranging from regulatory compliance monitoring to business intelligence.
Necessary measures
Authors: Baker Wade H. , Rees Loren Paul , Tippett Peter S.
Published: September 2007

Use measurable, reliable real-world metrics to improve information security decision making.
Leveraging the flexibility of your data warehouse
Authors: Goeke Richard J. , Faley Robert H.
Published: September 2007

How data warehouse flexibility affects its use.
Deterring internal information systems misuse
Authors: D'Arcy John , Hovav Anat
Published: September 2007

Deterring employee intentions to misuse computer systems requires complementary technical and procedural controls.
Does copyright law need to be reformed?
Authors: Samuelson Pamela
Published: September 2007

Considering the issues involved in developing a simplified new copyright law and associated administrative mechanisms.
Why we compete in DARPA's Urban Challenge autonomous robot race
Authors: Thrun Sebastian
Published: September 2007

The robots will have to find their own way, sensing and predicting their whereabouts through automated perception, planning, and control.
Few useful considerations for maintaining software components and component-based systems
Authors: Grover P. S. , Kumar Rajesh , Sharma Arun
Published: September 2007

Component-Based Systems (CBS) maintenance may require several activities different than normal applications, such as upgrading the functionality of black-box components (for which code may not be available), replacement of older version components with the new ones for better and improved functionality, tracing the problem of compatibility between the new components with system, and so on. The focus of this paper is on investigating several issues and concerns about maintainability of component-based systems. It also explores the acceptance of maintainability characteristics and sub-characteristics as defined in ISO9126 quality model for CBS. The paper proposes two new sub-characteristics, namely trackability and portability, to be included under the maintenance activity.
Post-development software architecture
Authors: Huang Gang
Published: September 2007

Software architecture (SA) plays an important role in software development. Since the lifecycle stages post development become more and more important and face with many challenges similar to the development, it is a natural idea to introduce or extend SA into the stages post development. In this paper, we present our practices and experiences on applying software architecture into the deployment and maintenance of J2EE (Java 2 Platform Enterprise Edition) applications, including the tool and principles of SA-based J2EE deployment and SA-based J2EE online maintenance. It demonstrates that 1) SA can help to achieve a holistic, fine-grained and automated deployment of large-scale distributed systems by visualizing the structure of the system to be deployed; 2) SA can provide an understandable, operational and global view for online maintenance by organizing the fragmented and trivial management mechanisms; 3) Extending SA into the stages post development makes it possible that the whole lifecycle of a software system can be governed by SA with many benefits, e.g. consistency, traceability, responsiveness, etc.
UML based embedded documentation for semi-automatic software development
Authors: Marovac Nenad
Published: September 2007

A few years ago we introduced a concept of "Embedded Software Documentation". This embedded documentation consists of special documenting structures referred to as Flagged Sentences. The purpose of Flagged Sentences is to assists us in reading and understanding software programs and their individual components during the maintenance of these programs and reuse of the components. This embedded documentation also helps us in functional decomposition of given problems and design of related computer programs and in ensuring the consistency of interfaces within these programs. After the introduction of Object Oriented Modeling and Design, we expanded the concept of Flagged Sentences to incorporate a specification and classification mechanism based on Object Oriented Modeling and Design. This paper presents new extensions to deal with both: UML language for modeling of problems and software components implementing solutions to these problems, and Unified Process for iterative development of software systems. The basic objective in the current expansion of Flagged Sentences is to accommodate Object Oriented Modeling using UML, and to communicate all the necessary information to tasks that are part of modern and efficient development environments for software production. The information is provided in a format that is easy to extract and automatically organize, classify and use. The information includes data about application domains, problems to be solved, the associated software systems being developed and the related documentations.
Failure-driven software safety
Authors: Riehle Richard
Published: September 2007

Software safety and software risk management are two of the most important facets of modern software engineering. To understand safety requires that we understand first what is not safe. This paper examines the concept of failure in software engineering and describes an approach to failure-driven software design (FDSD).
Surfing the net for software engineering notes
Authors: Doernhoefer Mark
Published: September 2007

A good user interface is key to most programs. Designing an intuitive Graphical User Interface (GUI) that makes it easy for users to get information in to and out of your application is a hallmark of a killer app. Most software engineers are not graphic designers and most graphic designers are not software engineers and therein lies the problem. In this month's article I hope to provide software engineers with advice on graphic design and introduce graphic designers to some software tools that will help them realize their design in code. If you happen to be a graphic designer and a software engineer, you may find some useful tools and tips at the sites listed below.
Assessment of Contemporary Modularization Techniques - ACoM'07
Authors: Garcia Alessandro , Greenwood Phil , Heineman George , Walker Robert , Cai Yuanfang , Yang Hong Yul , Baniassad Elisa , Lopes Cristina Videira , Schwanninger Christa , Zhao Jianjun
Published: September 2007

The effective assessment of emerging modularization technologies plays a pivotal role on: (i) a better understanding of their real benefits and drawbacks when compared to conventional development techniques, and (ii) their effective transfer to mainstream software development. This report is intended to summarize the results of the 1st International Workshop on Assessment of Contemporary Modularization Techniques (ACoM'07) held in Minneapolis, USA, May 22, 2007, as part of the 29th International Conference on Software Engineering (ICSE'07). The main purpose of this workshop was to share and pool the collective experience of people interested in and actively working on assessment of innovative modularization techniques. The workshop consisted of an opening presentation, several paper presentations organized into three technical sessions, and four discussion groups. During the workshop presentations and discussions, the authors and participants directly and indirectly reviewed ongoing and previous work and debated a number of important issues on contemporary modularity assessment. The ACoM'07 website, including the electronic version of this report, can be found at . We begin by presenting an overview of our goals and the workshop structure, and then focus on the workshop technical program and results.
Post-workshop report for the Third International Workshop on Software Engineering for High Performance Computing Applications (SE-HPC 07)
Authors: Carver Jeffrey
Published: September 2007

This is the report from a one-day workshop that took place on Saturday, May 26, 2007 as part of the International Conference on Software Engineering in Minneapolis, MN, USA.
Protein Secretion in Gram-Negative Bacteria via the Autotransporter Pathway
Authors: Dautin Nathalie , Bernstein Harris D.
Published: September 2007

Autotransporters are a large and diverse superfamily of proteins produced by pathogenic gram-negative bacteria that are composed of an N-terminal passenger domain, which typically harbors a virulence function, and a C-terminal β domain. It has long been known that the β domain anchors the protein to the outer membrane and facilitates transport of the passenger domain into the extracellular space. Despite the apparent simplicity of the autotransporter pathway, several aspects of autotransporter biogenesis remain poorly understood, most notably the mechanism by which the passenger domain is translocated across the outer membrane. Here we review recent evidence that the enormous sequence diversity of both passenger and β domains belies a remarkable conservation of structure. We also discuss insights into each stage of autotransporter biogenesis that have emerged from recent structural, biochemical, and imaging studies.
Cytoskeletal Elements in Bacteria
Authors: Graumann Peter L.
Published: September 2007

All cytoskeletal elements known from eukaryotic cells are also present in bacteria, where they perform vital tasks in many aspects of the physiology of the cell. Bacterial tubulin (FtsZ), actin (MreB), and intermediate filament (IF) proteins are key elements in cell division, chromosome and plasmid segregation, and maintenance of proper cell shape, as well as in maintenance of cell polarity and assembly of intracellular organelle-like structures. Although similar tasks are performed by eukaryotic cytoskeletal elements, the individual functions of FtsZ, MreBs, and IFs are different from those performed by their eukaryotic orthologs, revealing a striking evolutional plasticity of cytoskeletal proteins. However, similar to the functions of their eukaryotic counterparts, the functions conferred by bacterial cytoskeletal proteins are driven by their ability to form dynamic filamentous structures. Therefore, the cytoskeleton was a prokaryotic invention, and additional bacteria-specific cytoskeletal elements, such as fibril and MinD-type ATPases, that confer various functions in cell morphology and during the cell cycle have been observed in prokaryotes. The investigation of these elements will give fundamental information for all types of cells and can reveal the molecular mode of action of cytoskeletal, filament-forming proteins.
Increased hypothalamic-pituitary-adrenal axis activity and hepatic insulin resistance in low-birth-weight rats
Authors: Buhl Esben S. , Neschen Susanne , Yonemitsu Shin , Rossbacher Joerg , Zhang Dongyan , Morino Katsutaro , Flyvbjerg Allan , Perret Pascale , Samuel Varman , Kim Jung , Cline Gary W. , Petersen Kitt Falk
Published: September 2007

Individuals born with a low birth weight (LBW) have an increased prevalence of type 2 diabetes, but the mechanisms responsible for this association are unknown. Given the important role of insulin resistance in the pathogenesis of type 2 diabetes, we examined insulin sensitivity in a rat model of LBW due to intrauterine fetal stress. During the last 7 days of gestation, rat dams were treated with dexamethasone and insulin sensitivity was assessed in the LBW offspring by a hyperinsulinemic euglycemic clamp. The LBW group had liver-specific insulin resistance associated with increased levels of PEPCK expression. These changes were associated with pituitary hyperplasia of the ACTH-secreting cells, increased morning plasma ACTH concentrations, elevated corticosterone secretion during restraint stress, and an ∼70% increase in 24-h urine corticosterone excretion. These data support the hypothesis that prenatal stress can result in chronic hyperactivity of the hypothalamic-pituitary-adrenal axis, resulting in increased plasma corticosterone concentrations, upregulation of hepatic gluconeogenesis, and hepatic insulin resistance.
Recovery of labeled CO2 from acetate in severely burned children
Authors: Fram Ricki Y. , Cree Melanie G. , Chinkes David L. , Herndon David N. , Wolfe Robert R.
Published: September 2007

The purpose of this study was to determine the fractional recovery rate of labeled CO2 in the breath of severely burned children. This information is needed to perform tracer studies of substrate oxidation using carbon-labeled fatty acids. Nine children, ages 4–14 yr with massive burns participated in the study. All experiments were performed 7 days post burn after an overnight fast. A primed (60 μmol/kg), constant (2.0 μmol·kg−1·min−1) infusion of [1,2-13C]acetate was given during a 4-h basal period and during a 4-h hyperinsulinemic euglycemic clamp. A priming dose (150 μmol/kg) of NaH13CO3 was given at the beginning of the study. Breath samples were collected every 10 min during the last 40 min of each period. Indirect calorimetry was performed during the last 30 min of each period. The isotopic enrichment of 13CO2 was determined by isotope ratio-mass spectrometry, and total CO2 excretion was measured by indirect calorimetry. The fractional recovery of acetate label was 0.89 ± 0.05 and 0.88 ± 0.04 during the basal state and clamp, respectively. We conclude that the fractional recovery of labeled acetate in severely burned children is approximately three times the recovery of a nonburned adult and similar to the value in exercising adults. The high recovery rate reflects the rapid turnover of the TCA cycle in burned children relative to the rate of exchange reactions. Minimal correction of expired CO2 data is needed in this circumstance to quantify fatty acid oxidation using 13C-labeled fatty acids.
Effect of liver fat on insulin clearance
Authors: Kotronen Anna , Vehkavaara Satu , Seppälä-Lindroos Anneli , Bergholm Robert , Yki-Järvinen Hannele
Published: September 2007

A fatty liver is associated with fasting hyperinsulinemia, which could reflect either impaired insulin clearance or hepatic insulin action. We determined the effect of liver fat on insulin clearance and hepatic insulin sensitivity in 80 nondiabetic subjects [age 43 ± 1 yr, body mass index (BMI) 26.3 ± 0.5 kg/m2]. Insulin clearance and hepatic insulin resistance were measured by the euglycemic hyperinsulinemic (insulin infusion rate 0.3 mU·kg−1·min−1for 240 min) clamp technique combined with the infusion of [3-3H]glucose and liver fat by proton magnetic resonance spectroscopy. During hyperinsulinemia, both serum insulin concentrations and increments above basal remained ∼40% higher ( P < 0.0001) in the high (15.0 ± 1.5%) compared with the low (1.8 ± 0.2%) liver fat group, independent of age, sex, and BMI. Insulin clearance (ml·kg fat free mass−1·min−1) was inversely related to liver fat content ( r = −0.52, P < 0.0001), independent of age, sex, and BMI ( r = −0.37, P = 0.001). The variation in insulin clearance due to that in liver fat (range 0–41%) explained on the average 27% of the variation in fasting serum (fS)-insulin concentrations. The contribution of impaired insulin clearance to fS-insulin concentrations increased as a function of liver fat. This implies that indirect indexes of insulin sensitivity, such as homeostatic model assessment, overestimate insulin resistance in subjects with high liver fat content. Liver fat content correlated significantly with fS-insulin concentrations adjusted for insulin clearance ( r = 0.43, P < 0.0001) and with directly measured hepatic insulin sensitivity ( r = −0.40, P = 0.0002). We conclude that increased liver fat is associated with both impaired insulin clearance and hepatic insulin resistance. Hepatic insulin sensitivity associates with liver fat content, independent of insulin clearance.
Glucose homeostasis, insulin secretion, and islet phospholipids in mice that overexpress iPLA2β in pancreatic β-cells and in iPLA2β-null mice
Authors: Bao Shunzhong , Jacobson David A. , Wohltmann Mary , Bohrer Alan , Jin Wu , Philipson Louis H. , Turk John
Published: September 2007

Studies with genetically modified insulinoma cells suggest that group VIA phospholipase A2(iPLA2β) participates in amplifying glucose-induced insulin secretion. INS-1 insulinoma cells that overexpress iPLA2β, for example, exhibit amplified insulin-secretory responses to glucose and cAMP-elevating agents. To determine whether similar effects occur in whole animals, we prepared transgenic (TG) mice in which the rat insulin 1 promoter (RIP) drives iPLA2β overexpression, and two characterized TG mouse lines exhibit similar phenotypes. Their pancreatic islet iPLA2β expression is increased severalfold, as reflected by quantitative PCR of iPLA2β mRNA, immunoblotting of iPLA2β protein, and iPLA2β enzymatic activity. Immunofluorescence microscopic studies of pancreatic sections confirm iPLA2β overexpression in RIP-iPLA2β-TG islet β-cells without obviously perturbed islet morphology. Male RIP-iPLA2β-TG mice exhibit lower blood glucose and higher plasma insulin concentrations than wild-type (WT) mice when fasting and develop lower blood glucose levels in glucose tolerance tests, but WT and TG blood glucose levels do not differ in insulin tolerance tests. Islets from male RIP-iPLA2β-TG mice exhibit greater amplification of glucose-induced insulin secretion by a cAMP-elevating agent than WT islets. In contrast, islets from male iPLA2β-null mice exhibit blunted insulin secretion, and those mice have impaired glucose tolerance. Arachidonate incorporation into and the phospholipid composition of RIP-iPLA2β-TG islets are normal, but they exhibit reduced Kv2.1 delayed rectifier current and prolonged glucose-induced action potentials and elevations of cytosolic Ca2+concentration that suggest a molecular mechanism for the physiological role of iPLA2β to amplify insulin secretion.
Effects of testosterone and estradiol on cutaneous vasodilation during local warming in older men
Authors: Sokolnicki Lynn A. , Khosla Sundeep , Charkoudian Nisha
Published: September 2007

Microvascular vasodilation in humans can become impaired with age, leading to cardiovascular diseases ranging from mild to life-threatening. Reproductive hormones may confer some protection on the vascular system in women; however, it is unclear whether the same is true in men. Our goal was to evaluate the impact of four hormonal conditions (testosterone only, estradiol only, testosterone and estradiol, no testosterone and no estradiol) on microvascular vasodilator responsiveness in the skin of older men. We hypothesized that in older healthy men estradiol promotes cutaneous microvascular dilation during local warming of the skin and that testosterone inhibits this dilation. We measured skin blood flow using laser Doppler flowmetry during 35 min of cutaneous local warming to 42°C in 52 healthy men (average age 67 ± 1 yr). Subjects were randomized to one of the four hormonal conditions and were studied before and after hormone treatments. The endothelium-dependent vasodilator response to local warming was not different among groups either before or after hormone treatment. For example, with testosterone-only treatment this vasodilator response was 220 ± 13 AU, and with estrogen only the response averaged 246 ± 12 AU ( P > 0.05). We conclude that, within the doses employed in the present study, testosterone and estradiol did not consistently alter cutaneous vasodilator responsiveness in healthy older men.
Baroreflexes of the rat. IV. ADN-evoked responses at the NTS
Authors: Tang Xiaorui , Dworkin Barry R.
Published: September 2007

In a long-term (7–21 days) neuromuscular blocked (NMB) rat preparation, using precise single-pulse aortic depressor nerve (ADN) stimulation and stable chronic evoked response (ER) recordings from the dorsal-medial solitary nucleus (dmNTS), two different response patterns were observed: continuous and discrete. For the continuous pattern, activity began ∼3 ms after the stimulus and persisted for 45 ms; for the discrete pattern, two complexes were separated by a gap from ∼17 to 25 ms. The early complex was probably transmitted via A-fibers: it had a low stimulus current threshold and an average conduction velocity (CV) of 0.58–5.5 m/s; the high threshold late (HTL) complex had a CV = 0.26–0.58 m/s. The average stimulus amplitude-ER magnitude transduction curves for the A and HTL complexes were sigmoidal. For individual rats, in the linear range, mean r2 = 0.96 ± 0.03 for both complexes. The average stimulus amplitude vs. the systolic blood pressure change (ΔsBP) transduction curve was also approximately linear; however, for individual rats, the relationship was not consistently reliable: mean r2 = 0.48 ± 0.19. Approximately 90% of recording sites had respiratory, and 50% had cardiac synchronism. The NMB preparation is useful for studying central baroreflex mechanisms that operate on time scales of days or weeks, such as adaptation and other kinds of neural plasticity.
Leukocytes of exceptionally old persons display ultra-short telomeres
Authors: Kimura M. , Barbieri M. , Gardner J. P. , Skurnick J. , Cao X. , van Riel N. , Rizzo M. R. , Paoliso G. , Aviv A.
Published: September 2007

With a view to understanding the association between leukocyte telomere length and the human lifespan, we performed genome-wide telomere length analyses by the terminal restriction fragment length (TRFL) and single molecule telomere length analysis (STELA) of the X and Y chromosomes in leukocytes of exceptionally old (aged 90–104 yr) and younger (aged 23–74 yr) individuals. We found that the mean TRFL of 82 exceptionally old individuals was within a range projected by age-dependent TRFL attrition of 99 younger individuals. However, compared with the younger individuals, exceptionally old persons exhibited peaking of the TRFL distribution with overrepresentation of ultra-short telomeres. These findings were confirmed by the STELA. Women had longer mean TRFL than men (6.10 vs. 5.86 kb), and exceptionally old women exhibited fewer ultra-short telomeres than exceptionally old men. Our results have implications for gerontological studies of the limitation of lifespan in humans.
Programmed metabolic syndrome: prenatal undernutrition and postweaning overnutrition
Authors: Desai Mina , Babu Jooby , Ross Michael G.
Published: September 2007

Maternal nutrient restriction results in intrauterine growth restriction (IUGR) newborns that develop obesity despite normal postweaning diet. The epidemic of metabolic syndrome is attributed to programmed “thrifty phenotype” and exposure to Western diets. We hypothesized that programmed IUGR newborns would demonstrate greater susceptibility to obesity and metabolic abnormalities in response to high-fat diet. From day 10 to term gestation and lactation, control pregnant rats received ad libitum (AdLib) food, whereas study rats were 50% food restricted (FR). Cross-fostering techniques resulted in three offspring groups: control (AdLib/AdLib), FR during pregnancy (FR/AdLib), and FR during lactation (AdLib/FR). At 3 weeks, offspring were weaned to laboratory chow or high-fat calorie diet (9% vs. 17% calorie as fat). Body composition, appetite hormones, and glucose and lipid profiles were determined in 9-mo-old male and female offspring. High-fat diet had no effect on body weight of AdLib/AdLib, but significantly increased weights of FR/AdLib and AdLib/FR offspring. High-fat diet significantly increased body fat, reduced lean body mass, and accentuated plasma leptin but not ghrelin levels in both sexes in all groups. In males, high-fat diet caused a significant increase in glucose levels in all three groups with increased insulin levels in AdLib/AdLib and AdLib/FR, but not in FR/AdLib. In females, high-fat diet had no effect on glucose but significantly increased basal insulin among all three groups. High-fat diet caused hypertriglyceridemia in all three groups although only food-restricted females exhibited hypercholesterolemia. Sex and offspring phenotype-associated effects of high-fat diet indicate differing pathophysiologic mechanisms that require specific therapeutic approaches.
Renal calcinosis and stone formation in mice lacking osteopontin, Tamm-Horsfall protein, or both
Authors: Mo Lan , Liaw Lucy , Evan Andrew P. , Sommer Andre J. , Lieske John C. , Wu Xue-Ru
Published: September 2007

Although often supersaturated with mineral salts such as calcium phosphate and calcium oxalate, normal urine possesses an innate ability to keep them from forming harmful crystals. This inhibitory activity has been attributed to the presence of urinary macromolecules, although controversies abound regarding their role, or lack thereof, in preventing renal mineralization. Here, we show that 10% of the mice lacking osteopontin (OPN) and 14.3% of the mice lacking Tamm-Horsfall protein (THP) spontaneously form interstitial deposits of calcium phosphate within the renal papillae, events never seen in wild-type mice. Lack of both proteins causes renal crystallization in 39.3% of the double-null mice. Urinalysis revealed elevated concentrations of urine phosphorus and brushite (calcium phosphate) supersaturation in THP-null and OPN/THP-double null mice, suggesting that impaired phosphorus handling may be linked to interstitial papillary calcinosis in THP- but not in OPN-null mice. In contrast, experimentally induced hyperoxaluria provokes widespread intratubular calcium oxalate crystallization and stone formation in OPN/THP-double null mice, while completely sparing the wild-type controls. Whole urine from OPN-, THP-, or double-null mice all possessed a dramatically reduced ability to inhibit the adhesion of calcium oxalate monohydrate crystals to renal epithelial cells. These data establish OPN and THP as powerful and functionally synergistic inhibitors of calcium phosphate and calcium oxalate crystallization in vivo and suggest that defects in either molecule may contribute to renal calcinosis and stone formation, an exceedingly common condition that afflicts up to 12% males and 5% females.
Rapid Adaptation to Scaled Changes of the Mechanical Environment
Authors: Hinder Mark R. , Milner Theodore E.
Published: September 2007

We investigated adaptation to simple force field scaling to determine whether the same strategy is used as during adaptation to more complex changes in the mechanical environment. Subjects initially trained in a force field, consisting of a rightward lateral force with a parabolic spatial profile (PF). The field strength was then unexpectedly increased or decreased (ΔPF) for repeated sets of five consecutive trials, with intervening PF trials. Stiff elastic walls, which prevented lateral movement of the arm, randomly replaced 25% of ΔPF trials. Lateral deviation on ΔPF trials and lateral force against the elastic walls were used to assess the extent to which feedforward adaptations could be attributed to changes in lateral force or increased stiffness of the arm. When force field strength was increased or decreased hand paths were perturbed to the right or left, respectively. Performance error was significantly reduced between the first and second ΔPF trial positions of the set, whereas the lateral force impulse exerted against the elastic walls did not change until the third trial position. The lateral force was scaled upward or downward in response to the change in force field strength, suggesting a gradual change in the internal model. The results support a dual strategy of cocontraction (increased stiffness) and internal model modification. The development of an accurate internal model is a slower process than cocontraction and error reduction. This may explain the need to represent motor learning as two parallel processes with varying timescales, as recently proposed by Smith and colleagues.
Receptive Field for Dorsal Cochlear Nucleus Neurons at Multiple Sound Levels
Authors: Bandyopadhyay Sharba , Reiss Lina A. J. , Young Eric D.
Published: September 2007

Neurons in the dorsal cochlear nucleus (DCN) exhibit nonlinearities in spectral processing, which make it difficult to predict the neurons’ responses to stimuli. Here, we consider two possible sources of nonlinearity: nonmonotonic responses as sound level increases due to inhibition and interactions between frequency components. A spectral weighting function model of rate responses is used; the model approximates the neuron's rate response as a weighted sum of the frequency components of the stimulus plus a second-order sum that captures interactions between frequencies. Such models approximate DCN neurons well at low spectral contrast, i.e., when the SD (contrast) of the stimulus spectrum is limited to 3 dB. This model is compared with a first-order sum with weights that are explicit functions of sound level, so that the low-contrast model is extended to spectral contrasts of 12 dB, the range of natural stimuli. The sound-level–dependent weights improve prediction performance at large spectral contrast. However, the interactions between frequencies, represented as second-order terms, are more important at low spectral contrast. The level-dependent model is shown to predict previously described patterns of responses to spectral edges, showing that small changes in the inhibitory components of the receptive field can produce large changes in the responses of the neuron to features of natural stimuli. These results provide an effective way of characterizing nonlinear auditory neurons incorporating stimulus-dependent sensitivity changes. Such models could be used for neurons in other sensory systems that show similar effects.
Differential gene expression in functional classes of interstitial cells of Cajal in murine small intestine
Authors: Chen Hui , Ördög Tamás , Chen Junwei , Young David L. , Bardsley Michael R. , Redelman Doug , Ward Sean M. , Sanders Kenton M.
Published: September 2007

Interstitial cells of Cajal (ICC) have important functions in regulation of motor activity in the gastrointestinal tract. In murine small intestine, ICC are gathered in the regions of the myenteric plexus (ICC-MY) and the deep muscular plexus (ICC-DMP). These two classes of ICC have different physiological functions. ICC-MY are pacemaker cells and generate the slow-wave electrical rhythmicity of gastrointestinal organs. ICC-DMP form synaptic connections with the varicose nerve terminals of enteric motor neurons and are involved in reception and transduction of motor neurotransmission. Gene expression underlying specific functions of ICC classes is incompletely understood. In the present study, we used recently developed highly selective techniques to isolate the two functional ICC classes from enzymatically dispersed intestinal muscles by fluorescence-activated cell sorting. The transcriptomes of ICC-MY and ICC-DMP were investigated using oligonucleotide microarray analysis. Differential expression of functional groups of genes defined by standard gene ontology terms was also studied. There were substantial numbers of genes expressed more abundantly in ICC than in the tunica muscularis, and we also detected marked phenotypic differences between ICC-MY and ICC-DMP. Notably, genes related to cell junction, process guidance, and vesicle trafficking were upregulated in ICC. Consistent with their specific functions, metabolic and Ca2+transport genes were relatively upregulated in ICC-MY, whereas genes for signaling proteins involved in transduction of neurotransmitter functions were relatively upregulated in ICC-DMP. Our results may lead to the identification of novel biomarkers for ICC and provide directions for further studies designed to understand ICC function in health and disease.