bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the interdisciplinary connections of gossip-based systems
Authors: Costa Paolo , Gramoli Vincent , Jelasity Márk , Jesi Gian Paolo , Le Merrer Erwan , Montresor Alberto , Querzoni Leonardo
Published: November 2007

In recent years the labels "gossip" and "gossip-based" have been applied to an increasingly general class of algorithms, including approaches to information aggregation, overlay network management and clock synchronization. These algorithms are intuitively similar, irrespective of their purpose. Their distinctive features include relying on local information, being round-based and relatively simple, and having a bounded information transmission and processing complexity in each round. Our position is that this class can and should be significantly extended to involve algorithms from other disciplines that share the same or similar distinctive features, like certain parallel numerical algorithms, routing protocols, bio-inspired algorithms and cellular automata, to name but a few. Such a broader perspective would allow us to import knowledge and tools to design and understand gossip-based distributed systems, and we could also export accumulated knowledge to re-interpret some of the problems in other disciplines, such as vehicular traffic control. In this position paper we describe a number of areas that show parallels with gossip protocols. These example areas will hopefully serve as inspiration for future research. In addition, we believe that comparisons with other fields also helps clarify the definition of gossip protocols and represents a necessary first step towards an eventual formal definition.
Gossiping on MANETs
Authors: Friedman Roy , Gavidia Daniela , Rodrigues Luis , Viana Aline Carneiro , Voulgaris Spyros
Published: November 2007

Gossip protocols have emerged as a powerful technique for implementing highly scalable and robust services, such as information dissemination and aggregation. The fact that gossip protocols require very little or no structure to operate makes them particularly appealing to apply in dynamic systems, where topology changes are common (for instance, due to frequent faults or high churn rates). Therefore, gossip protocols seem particularly well fit to operate in wireless self-organizing networks. Unfortunately, these networks have a number of characteristics that impede the deployment of gossip protocols designed for wired networks. In this work we identify the inherent differences in communication between wired and wireless networks and their impact on the design and implementation of gossip protocols. In particular, our comparison includes drawing a distinction between the gossiping primitives suitable for each of these environments. In the context of this analysis, we conclude by presenting a list of open research questions.
Gossiping over storage systems is practical
Authors: Weatherspoon Hakim , Miranda Hugo , Iwanicki Konrad , Ghodsi Ali , Busnel Yann
Published: November 2007

Gossip-based mechanisms are touted for their simplicity, limited resource usage, robustness to failures, and tunable system behavior. These qualities make gossiping an ideal mechanism for storage systems that are responsible for maintaining and updating data in a mist of failures and limited resources (e.g., intermittent network connectivity, limited bandwidth, constrained communication range, or limited battery power). We focus on persistent storage systems that, unlike mere caches, are responsible for both the durability and the consistency of data. Examples of such systems may be encountered in many different environments, in particular: wide-area networks (constrained by limited bandwidth), wireless sensor networks (characterized by limited resources), and mobile ad hoc networks (suffering from intermittent connectivity). In this paper, we demonstrate the qualities of gossiping in these three respective environments.
The Next Big Thing
Authors: Neville-Neil George
Published: November 2007

Dear KV, I know you did a previous article where you listed some books to read. I would also consider adding How to Design Programs, available free on the Web. This book is great for explaining the process of writing a program. It uses the Scheme language and introduces FP. I think FP could be the future of programming. John Backus of the IBM Research Laboratory suggested this in 1977. Even Microsoft has yielded to FP by introducing FP concepts in C# with LINQ. Do you feel FP has a future in software development, or are we stuck with our current model of languages with increasing features?
Standardizing Storage Clusters
Authors: Goodson Garth , Susharla Sai , Iyer Rahul
Published: November 2007

Data-intensive applications such as data mining, movie animation, oil and gas exploration, and weather modeling generate and process huge amounts of data. File-data access throughput is critical for good performance. To scale well, these HPC (high-performance computing) applications distribute their computation among numerous client machines. HPC clusters can range from hundreds to thousands of clients with aggregate I/O demands ranging into the tens of gigabytes per second.
Review of “Beginning POJOs: From Novice to Professional by Brian Sam-Bodden”, Apress, 2006, $39.99, ISBN: 1590595963
Authors: Balaraman S.
Published: November 2007

Review of “Beginning POJOs: From Novice to Professional by Brian Sam-Bodden”, Apress, 2006, $39.99, ISBN: 1590595963
Calendar
Authors: Stanik John
Published: November 2007

Software Business
EDP auditing in the 1980's or the vanishing paper trail
Authors: Andersen Richard E.
Published: November 2007

This paper is designed to provide an overview of (1) traditional auditing methodology and (2) the reasons why these methods must be modified and adapted in order to cope with the "vanishing paper trail" inherent in today's (and tomorrow's) increasingly on-line, data base-oriented, distributed processing, EDP environment.

The three basic types off audits (general, administrative, and applications) will be discussed. Examples of flagrant, and not-so-flagrant, computer crimes will be presented. Practical and proposed solutions for the reduction of these types of DP crimes in the 1980's will be examined.

The major thrust of the paper, however, will address the importance of the applications-oriented audit. The paper will discuss the concept of Computer Management Technology (CMT), and show that this is in reality a type of on-going auditing task. Alternatives will be examined for measuring, managing and controlling key functional areas that have a definite interactive effect on the availability of resources and the performance of system components (or both) in a data processing installation.
Special note from the editors
Authors: Savvides Andreas , Martin Richard , Srivastava Mani
Published: November 2007

The following paper ("An Algorithm for Fast, Model-Free Tracking Indoors" by Aiyou Chen, Cristina Harko, Diane Lambert, and Phil Whiting) was reviewed and selected as part of the Special Issue on Localization, guest edited by Prof. Andreas Savvides (Yale University) and Prof. Richard Martin (Rutgers University). Due to reasons beyond our control, this paper could not be included with the other papers in the special issue in January 2007 (Volume 11, No. 1), and we apologize for that. Kindly refer to the January 2007 issue of MC
2
R for the Guest Editorial and the other papers.
Net-X
Authors: Chereddi Chandrakanth , Kyasanur Pradeep , Vaidya Nitin H.
Published: November 2007

The use of multiple wireless channels has been advocated as one approach for enhancing network capacity. In many scenarios, hosts will be equipped with fewer radio interfaces than available channels. Under these scenarios, several protocols, which require interfaces to switch frequently, have been proposed. However, implementing protocols which require frequent interface switching in existing operating systems is non-trivial. In this paper, we identify the features needed in the operating system kernel for supporting frequent interface switching. We present a new channel abstraction module to support frequent interface switching. We identify modifications to interface device drivers to reduce switching delay. The channel abstraction module and an example multichannel protocol that uses the module have been implemented in a multichannel multi-interface testbed. Our implementation efforts are part of the Net-X project which is aimed at developing operating system support for exploiting various forms of diversity available in a wireless network in the form of multiple channels, interfaces, transmission rates, transmission power-levels, etc.
Modeling fairness and starvation in concurrent systems
Authors: Bandyopadhyay Anup Kumar
Published: November 2007

Standard temporal logic is augmented and a new temporal quantifier viz.,
never
is defined. This augmented logic is integrated in Dijkstra's weakest precondition calculus. Definitions for fairness and starvation for concurrent systems in terms of weakest precondition are presented. According to the existing concept fairness for a transition rule asserts that if a rule remains continuously enabled (weak fairness) or repeatedly enabled (strong fairness), then it must be executed., where in the proposed definition fairness is related to the permission for execution where starvation relies upon actual execution. This definition is used to prove fairness of a given concurrent system. Through different examples it is shown that fairness is not the only prerequisite for starvation freedom. Available techniques use 'leads to' operator that forecasts system behavior where the proposed proof technique moves backward in time.
AFIS data compression
Authors: Zirkind Givon
Published: November 2007

This article describes the development and implementation of a data compression algorithm designed specifically for fingerprints, referred to as GBP compression. The algorithm is herein discussed. Data Compression algorithms can be designed for general applications, meaning the input data is unknown. This is more commonly referred to as generic data. [LI01] Or, data compression algorithms can be designed for specific applications. e.g. AFIS [Automated Fingerprint Identification Systems] "When the input is known, higher compression ratios can be achieved with the knowledge of the input data stream." To-date, the highest compression ratio for an unknown input data stream, for all data compression algorithms, is JPEG with an average compression ratio range of 1:17 -- 1:23. [PEN03] The algorithm herein discussed, has a compression ratio range of 1:68 -- 1:92. There is a value, time and place for each design method - generic or specific - depending upon a variety of factors. Due to the nature of the use of AFIS for law enforcement and incrimination as well as criminal conviction, there are social issues that make data integrity of paramount concern. This factor influences algorithm selection and design. A lossless algorithm is a must! Also, the nature of AFIS is such that it operates across borders and between states, municipalities and jurisdictions. In addition to the usual issues and resistance to accepting new technology, including software [e.g. resistance to change, fear of system failure, etc.], there are the issues of changing engineering standards [hardware and software] which are governmentally determined as well as governmental policy decisions. Likewise, the portability required in implementing a new algorithm, will have to deal with a variety of hardware and software; as well as be designed to integrate into existing systems. This integration must include the ability to incorporate existing JPEG data files, from existing police databases. This requires a handshaking of standards and conversion programs that maintain data integrity. In addition, there is an in depth discussion of the limits of compression with a novel perspective.
Risks to the public
Authors: Neumann Peter G.
Published: November 2007

Edited by Peter G. Neumann (Risks Forum Moderator and Chairman of the ACM Committee on Computers and Public Policy), plus personal contributions by others, as indicated. Opinions expressed are individual rather than organizational, and all of the usual disclaimers apply. We address problems relating to software, hardware, people, and other circumstances relevant to computer systems. To economize on space, we include pointers to items in the online Risks Forum: (R i j) denotes RISKS vol i number j. Cited RISKS items generally identify contributors and sources, together with URLs. Official RISKS archives are available at www.risks.org (which redirects to Newcastle and gets you nice html formatting and a search engine courtesy of Lindsay Marshall; http://catless.ncl.ac.uk/Risks/i.j.html gets you (R i j)) and at ftp://www.sri.com/risks.
Design of a high level language machine
Authors: Battarel G. J. , Chevance R. J.
Published: November 2007

This paper presents mechanisms to be realized on a basic, capability - based architecture, to support the execution of PL/1, COBOL and FORTRAN languages, while ensuring error confinement and facilitating error detection and categorization. The concept of domain is used in order to support various linking strategies. The addressing space of a task is structured according to three characteristics of its components: scope, lifetime and access rights. The semantics to be associated to data structures and data types are explored and a 3-address instruction set is proposed.
The evaluation of expressions in a storage-to-storage architecture
Authors: Myers Glenford J.
Published: November 2007

One intent of my earlier paper[1] against stack-oriented instruction sets was to revive some of the historical debate on instruction-set forms. Apparently this has been successful, since Schulthess and Kumprecht[2], and later Keedy[3], have been kind enough to continue the debate. Since I have already replied to Schulthess and Mumprecht[4], this paper is an answer to the issues raised by Keedy.
Computer programming for facilities treating developmentally disabled children
Authors: Nelson Ronald H.
Published: November 2007

In the mental health institution, the staff are generally divided into two areas: the administrators and the clinicals. "The administrative-programmatic objective is the make a general class of services available to a specific individual or group of individuals" (Hurder & Hurder, ND). Therefore, each group is interested in different kinds of data for different purposes.
Student response behaviors in an instrumented feedback environment
Authors: Kumar V. K. , Rogers James L.
Published: November 2007

Three sessions of an Educational Statistics course were taught in an instrumented feedback environment which allowed students to register up to twelve responses (e.g. "Repeat", "Please Summarize") at their initiative, or in response to instructor's queries. Comparison between instrumented and non-instrumented settings indicated no significant difference in overall response rate. However, it was observed that keysets did serve as another mode of responding, particularly for responses which need not be accompanied by oral responses, and for students who had difficulty with the course. Some software and hardware refinements are suggested to study the effects of student responses on systematically shaping instructor's behavior.
Evaluating a computer literacy curriculum
Authors: Kurshan Barbara L. , Sherman Thomas M.
Published: November 2007

A multi-measure validation procedure was employed to evaluate a computer literacy curriculum. The evaluation was based upon the assumption that a comparison of results from several validation techniques produces more conclusive evidence about transfer hypotheses generated for the curriculum. The evaluation process was enhanced by the development and use of a sequenced decision-making procedure through which validation data from many sources could be employed. The results of the evaluation were used to produce a validated and reproducible curriculum consisting of sixty-two specific computer literacy objectives relating to five major goals or objectives.
Evaluation of the cognitive goals of OZNAKI
Authors: Cohen Harvey A. , Green David G.
Published: November 2007

The OZNAKI Project applies cognitive goals to the design of TINY robotics languages and sequences of lessons in which students program simple robots and TV "block" graphics. One such lesson sequence, the "Projection Module", has been designed to emphasise "projection", a fundamental spatial ability. The course was evaluated in a study involving students aged 8 to 13 years. Experimental and control groups consisted of students matched by age, class, and spatial ability (measured by pre-test), with no previous OZNAKI experience. While the experimental group participated in OZNAKI lessons the control group had only their usual maths lessons. The pre- and post-tests took the form of individual Piagetian interviews with the primary school students, and multi-choice questionnaires with the junior high school students, thus giving two distinct studies. Significant enhancement of spatial abilities was found for the experimental group in both the primary and the secondary studies.
People in DP
Authors: Work Ann
Published: November 2007

Twenty years ago, applications were run one at a time in batch processing mode. To generate a report, a card deck was submitted. The results might not come back until the next day. Data was grouped by organizational component: there were accounting files, purchasing files, marketing files production files - each department had a different set of files. The same data might be represented in several files in different formats.
Wnt antagonism inhibits hepatic stellate cell activation and liver fibrosis
Authors: Cheng Jason H. , She Hongyun , Han Yuan-Ping , Wang Jiaohong , Xiong Shigang , Asahina Kinji , Tsukamoto Hidekazu
Published: November 2007

Activation of hepatic stellate cells (HSC), a key event in liver fibrosis, is caused by diminished adipogenic transcription. This study investigated whether Wnt signaling contributes to “antiadipogenic” activation of HSC and liver fibrogenesis. Culture-activated HSC from normal rats and HSC from cholestatic rat livers were examined for expression of Wnt, Frizzled (Fz) receptors, and coreceptors by quantitative PCR. Wnt signaling was assessed by nuclear β-catenin and T cell factor (TCF) promoter activity. Dickkopf-1 (Dkk-1), a Wnt coreceptor antagonist, was transduced by an adenoviral vector to assess the effects of Wnt antagonism on culture activation of HSC and cholestatic liver fibrosis in mice. Messenger RNA for canonical (Wnt3a and 10b) and noncanonical (Wnt4 and 5a) Wnt genes, Fz-1 and 2, and coreceptors [low-density lipoprotein-receptor-related protein (LRP)6 and Ryk] are increased ∼3–12-fold in culture-activated HSC compared with quiescent HSC. The nuclear β-catenin level and TCF DNA binding are markedly increased in activated HSC. TCF promoter activity is stimulated with Wnt1 but inhibited by Chibby, a protein that blocks β-catenin interaction with TCF, and by Dkk-1. Dkk-1 enhances peroxisome proliferator-activated receptor-γ (PPARγ)-driven PPAR response element (PPRE) promoter activity, a key adipogenic transcriptional parameter, abrogates agonist-stimulated contraction, and restores HSC quiescence in culture. High expression of Dkk-1 increases apoptosis of cultured HSC. Expression of Wnt and Fz genes is also induced in HSC isolated from experimental cholestatic liver fibrosis, and Dkk-1 expression ameliorates this form of liver fibrosis in mice. These results demonstrate antiadipogenic Wnt signaling in HSC activation and therapeutic potential of Wnt antagonism for liver fibrosis.
Stimulatory phosphorylation of cAMP-specific PDE4D5 by contractile agonists is mediated by PKC-dependent inactivation of protein phosphatase 2A
Authors: Murthy Karnam S. , Sriwai Wimolpak
Published: November 2007

Smooth muscle of the gut undergoes rhythmic cycles of contraction and relaxation. Various constituents in the pathways that mediate muscle contraction could act to cross-regulate cAMP or cGMP levels and terminate subsequent relaxation. We have previously shown that cAMP levels are regulated by PKA-mediated phosphorylation of cAMP-specific phosphodiesterase 3A (PDE3A) and PDE4D5; the latter is the only PDE4D isoform expressed in smooth muscle. In the present study we have elucidated a mechanism whereby cholecystokinin (CCK) and, presumably, other contractile agonists capable of activating PKC can cross-regulate cAMP levels. Forskolin stimulated PDE4D5 phosphorylation and PDE4D5 activity. CCK significantly increased forskolin-stimulated PDE4D5 phosphorylation and activity and attenuated forskolin-stimulated cAMP levels. The effect of CCK on forskolin-induced PDE4D5 phosphorylation and activity and on cAMP levels was blocked by the inhibitors of PLC or PKC and in cultured muscle cells by the expression of Gαq minigene. The effects of CCK on PDE4D5 phosphorylation, PDE4D5 activity, and cAMP levels were mimicked by low (1 nM) concentrations of okadaic acid, but not by a low (10 nM) concentration of tautomycin, suggesting involvement of PP2A. Purified catalytic subunit of PP2A but not PP1 dephosphorylated PDE4D5 in vitro. Coimmunoprecipitation studies demonstrated association of PDE4D5 with PP2A and the association was decreased by the activation of PKC. In conclusion, cAMP levels are cross-regulated by contractile agonists via a mechanism that involves PLC-β-dependent, PKC-mediated inhibition of PP2A activity that leads to increase in PDE4D5 phosphorylation and activity and inhibition of cAMP levels.
Endocannabinoids and Liver Disease. II. Endocannabinoids in the pathogenesis and treatment of liver fibrosis
Authors: Siegmund Sören V. , Schwabe Robert F.
Published: November 2007

Hepatic fibrosis is the response of the liver to chronic injury and is associated with portal hypertension, progression to hepatic cirrhosis, liver failure, and high incidence of hepatocellular carcinoma. On a molecular level, a large number of signaling pathways have been shown to contribute to the activation of fibrogenic cell types and the subsequent accumulation of extracellular matrix in the liver. Recent evidence suggests that the endocannabinoid system is an important part of this complex signaling network. In the injured liver, the endocannabinoid system is upregulated both at the level of endocannabinoids and at the endocannabinoid receptors CB1 and CB2. The hepatic endocannabinoid system mediates both pro- and antifibrogenic effects by activating distinct signaling pathways that differentially affect proliferation and death of fibrogenic cell types. Here we will summarize current findings on the role of the hepatic endocannabinoid system in liver fibrosis and discuss emerging options for its therapeutic exploitation.
Ghrelin suppresses cardiac sympathetic activity and prevents early left ventricular remodeling in rats with myocardial infarction
Authors: Soeki Takeshi , Kishimoto Ichiro , Schwenke Daryl O. , Tokudome Takeshi , Horio Takeshi , Yoshida Morikatsu , Hosoda Hiroshi , Kangawa Kenji
Published: November 2007

A recent study suggests that exogenous ghrelin administration might decrease renal sympathetic nerve activity in conscious rabbits. In the present study, we investigated whether ghrelin administration would attenuate left ventricular (LV) remodeling following myocardial infarction (MI) via the suppression of cardiac sympathetic activity. Ghrelin (100 μg/kg sc, twice daily, n = 15) or saline ( n = 15) were administered for 2 wk from the day after MI operation in Sprague-Dawley rats. The effects of ghrelin on cardiac remodeling were evaluated by echocardiographic, hemodynamic, histopathological, and gene analysis. In addition, before and after ghrelin (100 μg/kg sc, n = 6) was administered in conscious rats with MI, the autonomic nervous function was investigated by power spectral analysis obtained by a telemetry system. In ghrelin-treated rats, LV enlargement induced by MI was significantly attenuated compared with saline-treated rats. In addition, there was a substantial decrease in LV end-diastolic pressure and increases in the peak rate of the rise and fall of LV pressure in ghrelin-treated MI rats compared with saline-treated MI rats. Furthermore, ghrelin attenuated an increase in morphometrical collagen volume fraction in the noninfarct region, which was accompanied by the suppression of collagen I and III mRNA levels. Importantly, a 2-wk administration of ghrelin dramatically suppressed the MI-induced increase in heart rate and plasma norepinephrine concentration to the similar levels as in sham-operated controls. Moreover, acute administration of ghrelin to MI rats decreased the ratio of the low-to-high frequency spectra of heart rate variability ( P < 0.01). In conclusion, these data suggest the potential usefulness of ghrelin as a new cardioprotective hormone early after MI.
Alteration of deposition pattern and pulmonary response as a result of improved dispersion of aspirated single-walled carbon nanotubes in a mouse model
Authors: Mercer R. R. , Scabilloni J. , Wang L. , Kisin E. , Murray A. R. , Schwegler-Berry D. , Shvedova A. A. , Castranova V.
Published: November 2007

Nanoparticles have a fundamental dimension of <100 nm. However, on suspension in media, agglomerates of nanoparticles are the more common structure. This is particularly evident in prior intratracheal instillation or aspiration studies of single-walled carbon nanotubes (SWCNT), in which granulomatous lesions encased by epithelioid macrophages were produced by large agglomerates. In this study, we tested the hypothesis of whether exposure to more dispersed SWCNT structures would alter pulmonary distribution and response. A dispersed preparation of single-walled carbon nanotubes (DSWCNT) with a mean diameter of 0.69 μm was given by pharyngeal aspiration to C57BL/6 mice. Electron microscopy demonstrated a highly dispersed, interstitial distribution of DSWCNT deposits by 1 day postexposure. Deposits were generally <1 μm. Macrophage phagocytosis of DSWCNT was rarely observed at any time point. Lung responses were studied by lavage and morphometry at 1 h, 1 day, 7 day, and 1 mo after a single DSWCNT exposure of 10 μg/mouse. Lung sections and lavage cells demonstrated an early, transient neutrophilic and inflammatory phase that rapidly resolved and was similar to that observed with large agglomerates. No granulomatous lesions or epithelioid macrophages were detected. Morphometric measurement of Sirius red staining was used to assess the connective tissue response. The average thickness of connective tissue in alveolar regions was 0.10 ± 0.02, 0.09 ± 0.02, 0.10 ± 0.01, 0.48 ± 0.04, and 0.88 ± 0.19 μm for PBS and 1-h, 1-day, 7-day, and 1-mo postexposure groups, respectively. The results demonstrate that dispersed SWCNT are rapidly incorporated into the alveolar interstitium and that they produce an increase in collagen deposition.
Noninvasively determined muscle oxygen saturation is an early indicator of central hypovolemia in humans
Authors: Soller Babs R. , Yang Ye , Soyemi Olusola O. , Ryan Kathy L. , Rickards Caroline A. , Walz J. Matthias , Heard Stephen O. , Convertino Victor A.
Published: November 2007

Ten healthy human volunteers were subjected to progressive lower body negative pressure (LBNP) to the onset of cardiovascular collapse to compare the response of noninvasively determined skin and fat corrected deep muscle oxygen saturation (SmO2) and pH to standard hemodynamic parameters for early detection of imminent hemodynamic instability. Muscle SmO2and pH were determined with a novel near infrared spectroscopic (NIRS) technique. Heart rate (HR) was measured continuously via ECG, and arterial blood pressure (BP) and stroke volume (SV) were obtained noninvasively via Finometer and impedance cardiography on a beat-to-beat basis. SmO2and SV were significantly decreased during the first LBNP level (−15 mmHg), whereas HR and BP were late indicators of impending cardiovascular collapse. SmO2declined in parallel with SV and inversely with total peripheral resistance, suggesting, in this model, that SmO2is an early indicator of a reduction in oxygen delivery through vasoconstriction. Muscle pH decreased later, suggesting an imbalance between delivery and demand. Spectroscopic determination of SmO2is noninvasive and continuous, providing an early indication of impending cardiovascular collapse resulting from progressive reduction in central blood volume.
Effects of 30 min of aerobic exercise on gene expression in human neutrophils
Authors: Radom-Aizik Shlomit , Zaldivar Frank , Leu Szu-Yun , Galassetti Pietro , Cooper Dan M.
Published: November 2007

Relatively brief bouts of exercise alter gene expression in peripheral blood mononuclear cells (PBMCs), but whether exercise changes gene expression in circulating neutrophils (whose numbers, like PBMCs, increase) is not known. We hypothesized that exercise would activate neutrophil genes involved in apoptosis, inflammation, and cell growth and repair, since these functions in leukocytes are known to be influenced by exercise. Blood was sampled before and immediately after 30 min of constant, heavy (∼80% peak O2uptake) cycle ergometer exercise in 12 healthy men (19–29 yr old) of average fitness. Neutrophils were isolated using density gradients; RNA was hybridized to Affymetrix U133+2 Genechip arrays. With false discovery rate (FDR) <0.05 with 95% confidence, a total of 526 genes were differentially expressed between before and after exercise. Three hundred and sixteen genes had higher expression after exercise. The Jak/STAT pathway, known to inhibit apoptosis, was significantly activated (EASE score, P < 0.005), but 14 genes were altered in a way likely to accelerate apoptosis as well. Similarly, both proinflammatory (e.g., IL-32, TNFSF8, and CCR5) and anti-inflammatory (e.g., ANXA1) were affected. Growth and repair genes like AREG and FGF2 receptor genes (involved in angiogenesis) were also activated. Finally, a number of neutrophil genes known to be involved in pathological conditions like asthma and arthritis were altered by exercise, suggesting novel links between physical activity and disease or its prevention. In summary, brief heavy exercise leads to a previously unknown substantial and significant alteration in neutrophil gene expression.
Muscle-derived ROS and thiol regulation in muscle fatigue
Authors: Ferreira Leonardo F. , Reid Michael B.
Published: November 2007

Muscles produce oxidants, including reactive oxygen species (ROS) and reactive nitrogen species (RNS), from a variety of intracellular sources. Oxidants are detectable in muscle at low levels during rest and at higher levels during contractions. RNS depress force production but do not appear to cause fatigue of healthy muscle. In contrast, muscle-derived ROS contribute to fatigue because loss of function can be delayed by ROS-specific antioxidants. Thiol regulation appears to be important in this biology. Fatigue causes oxidation of glutathione, a thiol antioxidant in muscle fibers, and is reversed by thiol-specific reducing agents. N-acetylcysteine (NAC), a drug that supports glutathione synthesis, has been shown to lessen oxidation of cellular constituents and delay muscle fatigue. In humans, NAC pretreatment improves performance of limb and respiratory muscles during fatigue protocols and extends time to task failure during volitional exercise. These findings highlight the importance of ROS and thiol chemistry in fatigue, show the feasibility of thiol-based countermeasures, and identify new directions for mechanistic and translational research.
Galanin Is Up-Regulated in Colon Adenocarcinoma
Authors: Kim Kye Young , Kee Mee K. , Chong Seon Ah , Nam Myeong Jin
Published: November 2007

The early diagnosis of colorectal cancer and the early detection of recurrence are central to effective treatment, as prognosis is directly related to the stage of the disease. When colorectal cancer is diagnosed at an early, localized stage, 5-year survival is 90%. There is substantial interest in the identification of circulating human tumor-derived proteins in serum for the purposes of early cancer diagnosis. We have implemented an approach based on the analysis of microarray data for the identification of tumor proteins that may have utility as biomarkers in colon cancer. Expression analysis of microarray data obtained from a variety of 290 tumors and normal tissues revealed that galanin was maximally expressed in colon cancer. These findings were corroborated by real-time quantitative PCR, in which the colon cancer cell lines LOVO, HCT15, SW480, and SW620 cell showed significantly higher levels of galanin expression than did noncolon cancer cell lines. To evaluate galanin as a potential biomarker of colon cancer, a preliminary “training” set of serum from 40 healthy donors and 55 colon cancer patients was analyzed by ELISA. The data pattern was confirmed by an independent set of 90 masked serum samples: 24 from healthy donors and 66 from colon cancer patients. This result yielded a sensitivity of 69.7% [95% confidence interval (95% CI), 57.1-80.4], specificity of 75.0% (95% CI, 53.3-90.2), and positive predictive value of 88.5% (95% CI, 76.6-95.7). The galanin expression level was significantly increased with tumor size and tumor stage. These findings justify a prospective assessment of serum galanin protein as a screening tool for colon cancer. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2373–8)
Assessment of the Relation between Biomarkers for Smoking and Biomarkers for Acrylamide Exposure in Humans
Authors: Vesper Hubert W. , Bernert John T. , Ospina Maria , Meyers Tunde , Ingham Leigha , Smith Antoinette , Myers Gary L.
Published: November 2007

Smoking is an important source of acrylamide exposure in the general population. We assessed the relationship between hemoglobin adducts of acrylamide (HbAA) and glycidamide (HbGA) as biomarkers of acrylamide exposure and plasma cotinine (PC) as biomarkers of tobacco smoke exposure in 94 men and 67 women. The median (5th-95th percentile) biomarker concentrations (pmol/g Hb) in the group of individuals with PC concentrations of ≤10 ng/mL were 51 (29-155) and 34 (16-117) for HbAA and HbGA, respectively. They were significantly lower than those in the group of individuals with PC concentrations of >10 ng/mL [194 (87-403) and 107 (41-215) for HbAA and HbGA, respectively]. In individuals with PC concentrations of <1 ng/mL, HbAA and HbGA were similar to those observed in the group with PC values of ≤10 ng/mL. The intersubject variability was profoundly smaller in the group with PC values of ≤10 ng/mL compared with the group with PC values of >10 ng/mL. Although HbAA and HbGA could be categorized into distinguishable groups using PC concentration ranges commonly used to categorize presumed smokers and nonsmokers, no significant relationship was observed between these two biomarkers and PC within each group. The different exposure periods reflected by these biomarkers and the resulting different susceptibility to short-term variations in exposure patterns may in part explain these observations. The findings suggest that tobacco smoke exposure in individuals with PC values of <1 ng/mL has only a minimal effect on HbAA and HbGA. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2471–8)
Bronchial Epithelial Ki-67 Index Is Related to Histology, Smoking, and Gender, but Not Lung Cancer or Chronic Obstructive Pulmonary Disease
Authors: Miller York E. , Blatchford Patrick , Hyun Dae Sung , Keith Robert L. , Kennedy Timothy C. , Wolf Holly , Byers Tim , Bunn Paul A. , Lewis Marina T. , Franklin Wilbur A. , Hirsch Fred R. , Kittelson John
Published: November 2007

Purpose: To determine whether increased bronchial epithelial proliferation is associated with histology, smoking status, gender, age, chronic obstructive pulmonary disease (COPD), or lung cancer.

Experimental Design: Cross-sectional study of 113 subjects undergoing white light and autofluorescence bronchoscopy: 27 never smokers; 27 current or ex-smokers with normal spirometry; 31 current or ex-smokers with COPD; and 28 current, ex-, or never smokers with lung cancer. Ki-67 expresssion was determined by immunohistochemistry on all evaluable biopsy sites without carcinoma. Relationships between Ki-67 index (percentage of epithelial cells expressing Ki-67), demographic variables, smoking, histology, and the presence of COPD and/or lung cancer were determined.

Results: Results for both maximal and mean Ki-67 index are similar, so only the former are reported. Average maximal Ki-67 index was higher in current smokers than either ex-smokers or never smokers (48.0% versus 30.6% versus 22.6%; P < 0.001). Males had higher Ki-67 index than females (39.9% versus 23.6%; P < 0.001). Compared with subjects without disease (Ki-67 index = 30.0%), maximal Ki-67 index was not significantly elevated (P = 0.44) in subjects with either lung cancer (Ki-67 = 39.1%) or COPD (Ki-67 = 38.9%).

Conclusions: Smoking status, bronchial histology, and gender were significantly associated with Ki-67 index. No increase in Ki-67 index was found in the nonmalignant epithelium of patients with lung cancer or COPD. Although Ki-67 index may provide insight into the short-term effects of chemoprevention agents on cell proliferation, its lack of association with lung cancer or COPD raises question regarding its utility as a lung cancer risk biomarker. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2425–31)
The Association of Gastric Cancer Risk with Plasma Folate, Cobalamin, and Methylenetetrahydrofolate Reductase Polymorphisms in the European Prospective Investigation into Cancer and Nutrition
Authors: Vollset Stein Emil , Igland Jannicke , Jenab Mazda , Fredriksen Åse , Meyer Klaus , Eussen Simone , Gjessing Håkon K. , Ueland Per Magne , Pera Guillem , Sala Núria , Agudo Antonio , Capella Gabriel , Del Giudice Giuseppe , Palli Domenico , Boeing Heiner , Weikert Cornelia , Bueno-de-Mesquita H. Bas , Carneiro Fátima , Pala Valeria , Vineis Paolo , Tumino Rosario , Panico Salvatore , Berglund Göran , Manjer Jonas , Stenling Roger , Hallmans Göran , Martínez Carmen , Dorronsoro Miren , Barricarte Aurelio , Navarro Carmen , Quirós José R. , Allen Naomi , Key Timothy J. , Bingham Sheila , Linseisen Jakob , Kaaks Rudolf , Overvad Kim , Tjønneland Anne , Büchner Frederike L. , Peeters Petra H.M. , Numans Mattijs E. , Clavel-Chapelon Françoise , Boutron-Ruault Marie-Christine , Trichopoulou Antonia , Lund Eiliv , Slimani Nadia , Ferrari Pietro , Riboli Elio , González Carlos A.
Published: November 2007

Previous studies have shown inconsistent associations of folate intake and polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene with gastric cancer risk. Our nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort is the first prospective study of blood folate levels and gastric cancer. Gastric cancer cases (n = 247) and controls (n = 631) were matched for study center, age, sex, and time of blood donation. Two common single nucleotide polymorphisms of the MTHFR gene were determined, as were plasma concentrations of folate, cobalamin (vitamin B12), total homocysteine, and methylmalonic acid (cobalamin deficiency marker) in prediagnostic plasma. Risk measures were calculated with conditional logistic regression. Although no relations were observed between plasma folate or total homocysteine concentrations and gastric cancer, we observed a trend toward lower risk of gastric cancer with increasing cobalamin concentrations (odds ratio, 0.79 per SD increase in cobalamin; P = 0.01). Further analyses showed that the inverse association between cobalamin and gastric cancer was confined to cancer cases with low pepsinogen A levels (marker of severe chronic atrophic gastritis) at the time of blood sampling. The 677 C→T MTHFR polymorphism was not associated with gastric cancer, but we observed an increased risk with the variant genotype of the 1298 A→C polymorphism (odds ratio, 1.47 for CC versus AA; P = 0.04). In conclusion, we found no evidence of a role of folate in gastric cancer etiology. However, we observed increased gastric cancer risk at low cobalamin levels that was most likely due to compromised cobalamin status in atrophic gastritis preceding gastric cancer. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2416–24)
Oral Contraceptive Use and Risk of Breast Carcinoma In situ
Authors: Nichols Hazel B. , Trentham-Dietz Amy , Egan Kathleen M. , Titus-Ernstoff Linda , Hampton John M. , Newcomb Polly A.
Published: November 2007

There is some indication that oral contraceptive use may be associated with a small increase in risk of invasive breast cancer; however, oral contraceptive use in relation to breast carcinoma in situ (BCIS) has rarely been studied. We investigated oral contraceptive use in relation to risk of BCIS in a large population-based case-control study. Female residents of Wisconsin, Massachusetts, and New Hampshire aged 20 to 74 years with a new diagnosis of BCIS (n = 1,878) were identified from statewide tumor registries in 1997 to 2001. Age-matched female controls (n = 8,041) were randomly selected from population lists. Information on oral contraceptive use and other risk factors was collected during structured telephone interviews. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using logistic regression. In multivariate models, ever use of oral contraceptives was associated with a small and marginally significant increase in BCIS overall (OR, 1.11; 95% CI, 0.99-1.25) and for ductal carcinoma in situ (OR, 1.15; 95% CI, 1.01-1.31). No strong associations were detected according to age started, duration, time since first or last use, or oral contraceptive use relative to the first full-term pregnancy. The slightly increased risk of BCIS seemed limited to former users (OR, 1.13; 95% CI, 1.00-1.27) and women without a family history of breast cancer (OR, 1.16; 95% CI, 1.01-1.32 for ever versus never use). Consistent with invasive breast cancer, these results suggest that oral contraceptive use is at most a minor contributor to BCIS risk. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2262–9)
Prostate Cancer Risk and ESR1 TA, ESR2 CA Repeat Polymorphisms
Authors: McIntyre Matthew H. , Kantoff Philip W. , Stampfer Meir J. , Mucci Lorelei A. , Parslow Diane , Li Haojie , Gaziano J. Michael , Abe Miyako , Ma Jing
Published: November 2007

Background: Experimental evidence has suggested that estrogen receptor α (coded by the gene ESR1) might increase prostate cancer risk, whereas estrogen receptor β (coded by the gene ESR2) might reduce prostate cancer risk.

Methods: We investigated the relationship with prostate cancer risk of both a TA repeat polymorphism in the ESR1 5′ region, ESR1 (TA)n, and with a CA repeat polymorphism in intron 5 of ESR2, ESR2 (CA)n, in a case-control study (545 cases and 674 controls) nested in the Physicians' Health Study.

Results: Prostate cancer risk was highest for carriers of ESR1 (TA)24 and ESR1 (TA)25. Replacing one modal ESR1 (TA)14 allele with one ESR1 (TA)24 allele yielded an odds ratio of 1.42 (95% confidence interval, 1.00-2.00; P = 0.05). Replacing one ESR1 (TA)14 allele with one ESR1 (TA)25 allele yielded an odds ratio of 2.10 (95% confidence interval, 1.15-3.84; P = 0.02). ESR2 (CA)n showed no effects on prostate cancer risk.

Conclusions: The ESR1 (TA)n polymorphism might play a role in prostate cancer risk. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2233–6)
Frequency of Defective DNA Mismatch Repair in Colorectal Cancer among the Alaska Native People
Authors: Boardman Lisa A. , Lanier Anne P. , French Amy J. , Schowalter Karen V. , Burgart Lawrence J. , Koller Kathryn R. , McDonnell Shannon K. , Schaid Daniel J. , Thibodeau Stephen N.
Published: November 2007

The frequency of colorectal cancer (CRC) among the Alaska Native people is the highest of any ethnic group in the United States. In this study, CRC from 329 Alaska Native people (165 Eskimo, 111 Indians, and 53 Aleut) were evaluated for evidence of defective DNA mismatch repair (MMR) by testing tumors for altered protein expression (hMLH1, hMSH2, and hMSH6) and for the presence of microsatellite instability. Of the 329 samples tested, 46 (14%) showed both microsatellite instability and altered protein expression; 42 (91%) with a loss of hMLH1, 3 (7%) hMSH2, and 1 (2%) hMLH1/hMSH6. Tumors with loss of hMLH1 were further evaluated for hMLH1 promoter hypermethylation and for the presence of the BRAF-V600E mutation. Among cases tested, all 19 (100%) tumors among the Eskimo patients showed hMLH1 promoter hypermethylation, whereas this was the case for only 3 of the 7 (42%) tumors among the Aleut (P = 0.002) and 5 of the 10 (50%) tumors from the Indians (P = 0.002). The majority of hypermethylated cases (23 of 27) tested positive for the V600E alteration. Of the nine tumors from the Aleut and Indian patients that did not exhibit hMLH1 hypermethylation, eight tested negative for V600E. Overall, the frequency of defective MMR among the three groups was not statistically different (P = 0.75). However, the data suggest that the pathogenesis of CRC may differ between the three groups. The CRC with defective MMR among the Eskimo sample fit the typical profile for hMLH1-related cancer associated with sporadic CRC, whereas the pattern in the Aleut and Indian suggests the possibility that germ line hMLH1 mutations may be present. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2344–50)
Ascorbate and Dehydroascorbic Acid as Reliable Biomarkers of Oxidative Stress: Analytical Reproducibility and Long-term Stability of Plasma Samples Subjected to Acidic Deproteinization
Authors: Lykkesfeldt Jens
Published: November 2007

Lack of post-sampling stability of ascorbate and dehydroascorbic acid and failure to block their in vivo equilibrium have lowered their value as biomarkers of oxidative stress and limited the ability to further investigate their possible role in disease prevention. In the present article, analytic reproducibility was tested by repeated analysis of plasma aliquots from one individual over 4 years. The plasma was subjected to acidic deproteinization with an equal volume of 10% meta-phosphoric acid containing 2 mmol/L of EDTA and analyzed for ascorbate and dehydroascorbic acid by high-performance liquid chromatography with coulometric detection. In a parallel experiment, the stability of human plasma samples treated as above and stored at −80°C for 5 years was tested in a cohort of 131 individuals. No degradation or shift in the equilibrium between ascorbate and dehydroascorbic acid was observed in either of the experiments. In conclusion, ascorbate and dehydroascorbic acid could be adequately preserved in plasma stored at −80°C following acidic deproteinization with meta-phosphoric acid containing 2 mmol/L of EDTA. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2513–6)