bluuebunny/crossref_metadata_2025 huggingface dataset:
Microprogrammed control unit (MCU) programming reference manual
Authors: Roberts John D. , Ihnat J. , Smith W. R.
Published: November 2007

The MCU (Microprogrammed Control Unit) is a high-speed, executive, input-output (I/O) processor and interrupt handler for the NRL Signal Processing Element (SPE), a part of the All Applications Digital Computer (AADC). It is the job of the MCU to supervise all SPE elements and to direct and initiate all data transfers between these elements. Referring to Fig. 1, one can see that the MCU directs the SPAU (Signal Processing Arithmetic Unit) and the CC's (Channel Controllers) via the Z bus, and communicates with up to 8 buffer memories over its two channels to the SCU (Storage Control Unit). To better understand the importance of the MCU, one needs to briefly examine the functions of the other SPE elements.
Tom Swift and his electric bilingual grandmother
Authors: Manwell Tom , Daugherity Walter , Desch Sam , Stolurow Lawrence
Published: November 2007

We describe a prototype Computer Aided Instruction system for teaching Russian, which has been operational at Harvard University (Sept. 1970 to Sept. 1971), and at the State University of New York at Stony Brook (Sept. 1971 until present, depending on funds). The course allows the student to work his way through, choosing his own learning path, and the system provides "audit trails"; it gathers and analyzes data for basic study in the acquisition of a second language by individual students. Although the course stresses the Russian morphological system, the construction of the computer program is applicable to other languages and language teaching specialities.
The automation of introductory computer science courses
Authors: Nievergelt Jurg , Reingold Edward M. , Wilcox Thomas R.
Published: November 2007

In response to a large (currently 2000 students per semester) and increasing enrollment in introductory computer science courses, we have started a project to automate these courses on the PLATO IV Computer-Based Education system at the University of Illinois. The key components of our automated course are:

1. a library of lessons, covering several programming languages, computing techniques, and application areas

2. a completely self-contained interactive programming system for the preparation, execution and debugging of programs written by students in any of the languages covered by the lessons

3. a conversational advice-giving and information retrieval system to guide the student through the library of lessons, based on his goals and past performance.

The goals and current status of this project are described.
The virtual node layer
Authors: Brown Matthew , Gilbert Seth , Lynch Nancy , Newport Calvin , Nolte Tina , Spindel Michael
Published: November 2007

The Virtual Node Layer (VNLayer) programming abstraction provides programmable, predictable automata--virtual nodes--emulated by the low-level network nodes. This simplifies the design and rigorous analysis of applications for the wireless sensor network setting, as the layer can mask much of the uncertainty of the underlying components. In this paper, we define a general VNLayer architecture, and then use this framework to design a practical VNLayer implementation, optimized for real-world use. We then discuss our experience deploying this implementation on a testbed of hand-held computers, and in a custom-built packet-level simulator, and present a sample application--a virtual traffic light--to highlight the power and utility of our abstraction. We conclude with a survey of additional applications that are well-suited to this setting.
Kensho
Authors: Horey James , Maccabe Arthur B. , Mielke Angela
Published: November 2007

Recent research on sensor network programming architectures has managed to alleviate many common programming burdens, but has not fully addressed the problems associated with tasking and deployment. This has impeded the development of new multi-purpose sensor networks that require new software abstractions and mechanisms.

We present the design of a new software architecture for sensor networks that provides abstractions to explicitly address the issues of tasking and deployment. We also present an initial implementation of our architecture in simulation to investigate the potential memory overheads. Finally, we present a mobile tracking application to demonstrate how to use the abstractions provided by our architecture.
Architecture design principles to support adaptive service orchestration in WSN applications
Authors: Mechitov Kirill , Razavi Reza , Agha Gul
Published: November 2007

Our goal is to facilitate the development of sensor network applications in an open system, where applications arrive and leave dynamically and execute concurrently. We identify design principles that govern the creation of these systems, such as having a network-wide programming model, late binding and global resource management. In accordance with these principles, we assume that an application is modeled as a composite service, and propose an architecture for its adaptive orchestration on a WSN. Adaptivity here refers to automatic runtime selection of service implementations and network resources to execute the application specification in a resource-efficient and context-aware manner.
Address/memory management for a gigantic LISP environment or, GC considered harmful
Authors: White Jon L
Published: November 2007

The possibility of incredibly cheap, fantastically large media for storage gives rise to a realistic LISP memory management scheme under which GC may be postponed for days, or even indefinitely; the idea is encapsulated in the acronym "DDI" --- "GC? Don't Do It!". Tertiary memory is used to archive pages of the LISP environment which are perhaps reclaimable. but which have not been proven so; whereas the standard technique of "paging" is used to swap active data from the main memory to a secondary store such as magnetic disk. Some scenarios are presented considering a variety of currently-available technologies, and of one speculative possibility --- videodisc --- by which a requisite compactifying GC would be done "overnight", or over the weekend. With enough tertiary available, one design could last for over 12 years without a GC. "Write-once" memories, probably unusable for most applications, would not be at a disadvantage here.
Annotation-based program stepping
Authors: Parker Glen Randolph
Published: November 2007

Traditionally, stepping is achieved by modifying the evaluator. In the approach presented here, stepping is achieved by annotating the user's program with calls to stepping procedures. This provides greater flexibility in the selection of which program sections the user is interested in stepping. In addition, the sections not selected are executed without overhead. Stepped program sections are visually highlighted inside the user's program editor, providing a sense of context. Stepping control mechanisms, such as the ability to execute until a certain point and then step, permit the user to navigate through a program in a precise and flexible manner. A prototype stepper based on this approach has been implemented.
((lambda (discussions) (report on X3J13)) (work on an international standard))
Authors: Mathis Robert F.
Published: November 2007

X3J13 has always taken a very active interest in the progress of an international standard for Lisp. We would very much like to make sure that the national and international standards for Lisp turn out to be the same.
Programming environments
Authors: Foderaro John
Published: November 2007

In this issue we feature a description of Delphi Common Lisp, an enhanced version of Kyoto Common Lisp.
A bibliography on multiprocessor Lisp systems and applications
Authors: Van Deusen Mary S.
Published: November 2007

The following is a list of references on Multiprocessor Lisp systems and applications, compiled by Benamin Zorn (zorn@hecuba.berkeley.edu) with contributions by a number of others. It is currently maintained by Benjamin Zorn and TANAKA Tomoyuki (tanakat!jpntscvm.bitnet). Since it is preliminary, suggestions and additions are welcome. They should be sent to Zorn and Tanaka.
The scheme of things
Authors: Clinger William
Published: November 2007

Numbers are one of the greatest achievements of humanity. They are the product of many thousands of years of effort by the best minds of history---and prehistory. That effort continues, for our concept of numbers is, and will remain, unfinished.
Programming environments
Authors: Foderaro John , Layer D. Kevin
Published: November 2007

The editor is an important part of a LISP programming environment. In this paper we describe how we have integrated the GNU EMACS editor with ALLEGRO CL (previously known as Extended COMMON LISP). Parts of the interface between ALLEGRO CL and GNU EMACS can be used with any version of LISP, including FRANZ LISP. Other parts require a sophisticated multiprocessing facility, such as the one found in ALLEGRO CL or on LISP-machines. The interface can be obtained at no charge as described at the end of this paper.
The why of Y
Authors: Gabriel Richard P.
Published: November 2007

Did you ever wonder how Y works and how anyone could ever have thought of it? Do you feel like a Lisp weakling when some heavy-duty Scheme hacker kicks sand in your face by admiring Y in public? In this note I'll try to explain to you not only how it works, but how someone could have invented it. I'll use Scheme notation because it is easier to understand when functions passed as arguments are being applied. At the end, I'll show you Common Lisp equivalents of some of the Scheme code.
(algorithms)
Authors: Curtis Pavel
Published: November 2007

I have not been deluged with submissions for this column. I've gotten a few, but not enough to make it easy to put out another issue each quarter. Let me therefore repeat my charter:

The (algorithms) department consists of articles that fit into one or more of three broad categories:

• Annotated implementations of interesting and relevant algorithms; they should make particularly good or novel use of the unique features of the Lisp family of programming languages (e.g., closures, continuations, code as data, polymorphism),

• Annotated implementations of algorithms whose subject matter is the Lisp family of languages (e.g., code analysis tools, iteration facilities, generic arithmetic), and

• Discussion of performance issues, bench-marking, or implementation experiences for interesting algorithms written in or about the Lisp family of languages.
A study of LISP on a multiprocessor preliminary version
Authors: Nuth Peter , Halstead Robert
Published: November 2007

Parallel symbolic computation has attracted considerable interest in recent years. Research groups building multiprocessors for such applications have been frustrated by the lack of data on how symbolic programs run on a parallel machine. This report describes the behavior of Multilisp programs running on a shared memory multiprocessor. Data was collected for a set of application programs on the frequency of different instructions, the type of objects accessed, and where the objects were located in the memory of the multiprocessor. The locality of data references for different multiprocessor organizations was measured. Finally, the effect of different task scheduling strategies on the locality of accesses was studied. This data is summarized here, and compared to other studies of LISP performance on uniprocessors.
On listing list prefixes
Authors: Danvy Olivier
Published: November 2007

The Lisp Puzzles feature in Lisp Pointers, Volume 1, Number 6 proposed the following exercise: given a list, compute the list of its prefixes. Surprisingly, the solutions proposed in later issues all used intermediary copies and/or traversed the original list repeatedly. This note presents a higher-order solution that does not use copies and that traverses the original list only once. Further, this solution can be simply expressed by abstracting control procedurally.
Implementing queues in Lisp
Authors: Norvig Peter , Waters Richard C.
Published: November 2007

A queue is a data structure where items are entered one at a time and removed one at a time in the same order---i.e., first in first out. They are the same as stacks except that in a stack, items are removed in the reverse of the order they are entered---i.e., last in first out. Queues are most precisely described by the functions that act on them:

(make-queue) Creates and returns a new empty queue.
(algorithms)
Authors: Waters Richard C.
Published: November 2007

As can be seen from the dual addresses above, while maintaining an association with MIT, I have taken a permanent position with Mitsubishi Electric Research Laboratories (MERL). This newly formed laboratory is a subsidiary of Mitsubishi Electric Corporation. Its charter is to conduct basic research in computer science---demonstrating entirely new possibilities, rather than making incremental improvements in what is now possible.
A generic theoretical framework for modeling gossip-based algorithms
Authors: Fernandess Yaacov , Fernández Antonio , Monod Maxime
Published: November 2007

During the past 30 years of the Internet revolution, the Internet has become a major force of change with an enormous effect on civilization. Consequently, computer networks have evolved into more complex system and become virtually ubiquitous. This in turn, has given raise to a growing demand for scalable and reliable computer system architectures. Thus far, there has been enormous effort by the research community to introduce decentralized, simple, and scalable distributed systems to solve a wide range of problems. In this paper we explore one promising solution, which was initially inspired by mathematical models that investigate two everyday life phenomena, epidemics and gossip, which we used interchangeably throughout the paper. During the last century, mathematicians developed models to predict the rate of diseases spread, namely epidemics, using differential equations. In addition, researches developed discrete mathematics models to predict what we already know; rumors spread fast, namely gossip. It was thus natural to harness these models in order to design distributed systems that mimic the basic behavior of such fast spreading everyday life paradigms.
Compositional gossip
Authors: Rivière Étienne , Baldoni Roberto , Li Harry , Pereira José
Published: November 2007

Most proposed gossip-based systems use an ad-hoc design. We observe a low degree of reutilization among this proposals. We present how this limits both the systematic development of gossip-based applications and the number of applications that can benefit from gossip-based construction. We posit that these reinvent-the-wheel approaches poses a significant barrier to the spread and usability of gossip protocols.

This paper advocates a conceptual design framework based upon aggregating basic and predefined building blocks (B
2
). We show how to compose building blocks within our framework to construct more complex blocks to be used in gossip-based applications. The concept is further depicted with two gossip-based applications described using our building blocks.
Exploiting the synergy between gossiping and structured overlays
Authors: Ghodsi Ali , Haridi Seif , Weatherspoon Hakim
Published: November 2007

In this position paper we argue for exploiting the synergy between gossip-based algorithms and structured overlay networks (SON). These two strands of research have both aimed at building fault-tolerant, dynamic, self-managing, and large-scale distributed systems. Despite the common goals, the two areas have, however, been relatively isolated. We focus on three problem domains where there is an untapped potential of using gossiping combined with SONs. We argue for applying gossip-based membership for ring-based SONs---such as Chord and Bamboo---to make them handle partition mergers and loopy networks. We argue that small world SONs---such as Accordion and Mercury---are specifically well-suited for gossip-based membership management. The benefits would be better graph-theoretic properties. Finally, we argue that gossip-based algorithms could use the overlay constructed by SONs. For example, many unreliable broadcast algorithms for SONs could be augmented with anti-entropy protocols. Similarly, gossip-based aggregation could be used in SONs for network size estimation and load-balancing purposes.
Hard Disk Drives: The Good, the Bad and the Ugly!
Authors: Elerath Jon
Published: November 2007

HDDs are like the bread in a peanut butter and jelly sandwich—sort of an unexciting piece of hardware necessary to hold the “software.” They are simply a means to an end. HDD reliability, however, has always been a significant weak link, perhaps the weak link, in data storage. In the late 1980s people recognized that HDD reliability was inadequate for large data storage systems so redundancy was added at the system level with some brilliant software algorithms, and RAID (redundant array of inexpensive disks) became a reality. RAID moved the reliability requirements from the HDD itself to the system of data disks. Commercial implementations of RAID range from n+1 configurations (mirroring) to the more common RAID-4 and RAID-5, and recently to RAID-6, the n+2 configuration that increases storage system reliability using two redundant disks (dual parity). Additionally, reliability at the RAID group level has been favorably enhanced because HDD reliability has been improving as well.
Review of “Grid Computing Security by Anirban Chakrabarti”, Springer, 2007, $69.95, ISBN: 3540444920
Authors: Llanos Diego R.
Published: November 2007

Review of “Grid Computing Security by Anirban Chakrabarti”, Springer, 2007, $69.95, ISBN: 3540444920
Security techniques using SCF data
Authors: Youman Charles E.
Published: November 2007

The Statistical Collection File (SCF) contains data which can be used to detect unauthorized computer use. This paper gives examples of which record types to capture and how to extract and report this information using DEAR, GSEP and microfiche.
Requirements and design spaces of mobile medical care
Authors: Kulkarni Prajakta , Öztürk Yusuf
Published: November 2007

Pervasive care and chronic disease management to reduce institutionalization is a priority for most western countries. The realization of next generation ubiquitous and pervasive healthcare systems will be a challenging task, as these systems are likely to involve a complex structure. Such systems will consist of various devices, ranging from resource-constrained sensors and actuators to complex multimedia devices, supporting time critical applications. This is further compounded by cultural and socio-economical factors that must be addressed for next generation healthcare systems to be widely diffused and used. These factors have a direct impact on the system and security models and will require further understanding to encourage users to embrace and adopt the new technology. These models must capture not only the perceived value of the new technology and its ease of use, but most importantly the perceived risk of using this technology. This paper outlines the design space of pervasive health monitoring with body sensor networks and derives the requirements for connected pervasive medical care systems. Commercial and academic mobile medical sensor systems have been mapped to the requirements derived and a comparative analysis of state of the technology is given.
Predicting link quality using supervised learning in wireless sensor networks
Authors: Wang Yong , Martonosi Margaret , Peh Li-Shiuan
Published: November 2007

Routing protocols in sensor networks maintain information on neighbor states and potentially many other factors in order to make informed decisions. Challenges arise both in (a) performing accurate and adaptive information discovery and (b) processing/analyzing the gathered data to extract useful features and correlations. To address such challenges, this paper explores using supervised learning techniques to make informed decisions in the context of wireless sensor networks.

We investigate the design space of both offline learning and online learning and use link quality estimation as a case study to evaluate their effectiveness. For this purpose, we present MetricMap, a metric-based collection routing protocol atop MintRoute that derives link quality using classifiers learned in the training phase, when the traditional ETX approach fails. The offline learning approach is evaluated on a 30-node sensor network testbed, and our results show that MetricMap can achieve up to 300% improvement over MintRoute in data delivery rate for high data rate situations, with no negative impact on other performance metrics. We also explore the possibility of using online learning in this paper.
Research issues in software fault categorization
Authors: Ploski Jan , Rohr Matthias , Schwenkenberg Peter , Hasselbring Wilhelm
Published: November 2007

Software faults are a major threat for the dependability of software systems. When we intend to study the impact of software faults on software behavior, examine the quality of fault tolerance mechanisms, or evaluate diagnostic techniques, the issue of distinguishing fault categories and their frequency distribution arises immediately. This article surveys the literature that provides quantitative data on categories of software faults and discusses the applicability of these software fault category distributions to fault injection case studies.
On the economics of software
Authors: Wing Michael
Published: November 2007

Source is not precious. One can go to code.google.com and download source by the gigabyte. That's a lot. It would take most people an entire career to read and appreciate a gigabyte of code. Reading one chapter of a book per hour or a 50,000 word novel in twelve hours corresponds to reading 1 billion characters in 20 years, at 40 hours per week. Wading through gigabytes of code to find the few lines that one cares about can take a long time. On the other hand, applications are valuable, because they do specific things for specific users. Working apps consist of specific bodies of source.
A rider to "A Question of Semantics"
Authors: Steel Rod
Published: November 2007

Peter Denning, in the April '78 issue of CAN, voiced several very incisive observations concerning the generally slow rate at which commercial computer systems have incorporated the architectural knowledge currently available.
Towards an agenda for EFT research
Authors: Kraemer Kenneth L. , King John Leslie , Colton Kent
Published: November 2007

During the past decade the foundation has been laid for a major change in the payment and fund transfer system in American society. As technological advances are achieved, their application could eventually mean that the payments system will be based on digital impulses rather than on cash or paper checks. Preauthorization techniques, automated banking, and point of sale devices are already part of rapidly expanding new technology---electronic fund transfer (EFT) systems.
Cooperative efforts in individualized education
Authors: Modesitt Kenneth L.
Published: November 2007

Computer-based education (CBE) and personalized systems of instruction (PSI) are both remarkably successful tools for instructional delivery in content-based courses. However, CBE and PSI are both primarily designed to minister to the intellect of the student. That is appropriate within the university, but it is not sufficient.
Evaluating curricula for the teaching of programming
Authors: Ragsdale Ronald G.
Published: November 2007

Despite the great and continuing interest in methods of effective teaching of computer science concepts, especially programming, there is little hard data to back up the opinions that are so vigorously expressed. Moreover, most of those studies that have attempted to investigate programming instruction have been sufficiently flawed so as to render them of little use.

The first section of this paper deals with many of the flaws commonly found in studies of instruction in programming. These include non-random assignment of subjects, assuming identical instruction to different groups, experimenter bias, use of "available resources", short experimental treatments, home grown tests, and questionable analysis techniques.

The second section contains a description of the principles of good experimental design, using the concepts of internal and external validity. An experiment usually requires a compromise between the internal validity, which relates to control of experimental conditions, and the external validity, which has to do with the generalizability of the results.

The final section contains conclusions concerning initial steps that might be taken to rectify the problem caused by a lack of valid data. These steps include better and more objective quantification of the attributes of good programs and more integrative techniques for analyzing the results of multiple studies.
Learning and computers
Authors: Hoke Charles H.
Published: November 2007

The managerial grid has been used extensively in efforts to improve organizational management since the late 1950's. The underlying structure of grid theory has been of particular interest to the writer, an adult educator, during these past five years of accelerating awareness of and the need for increased knowledge of computer technology. Instrumented team learning from grid theory has provided a flexible and practical model for courses in management science in university and government settings; courses in systems theory, computer technology and information processing systems. It seemed appropriate that this successful learning model could be most useful in teaching students seeking an understanding of computerized information processing systems and of the computer as an indispensable tool of management.
Why does the gut choose apolipoprotein B48 but not B100 for chylomicron formation?
Authors: Lo Chun-Min , Nordskog Brian K. , Nauli Andromeda M. , Zheng Shuqin , vonLehmden Sarah B. , Yang Qing , Lee Dana , Swift Larry L. , Davidson Nicholas O. , Tso Patrick
Published: November 2007

Chylomicrons produced by the human gut contain apolipoprotein (apo) B48, whereas very-low-density lipoproteins made by the liver contain apo B100. To study how these molecules function during lipid absorption, we examined the process as it occurs in apobec-1 knockout mice (able to produce only apo B100; KO) and in wild-type mice (of which the normally functioning intestine makes apo B48, WT). Using the lymph fistula model, we studied the process of lipid absorption when animals were intraduodenally infused with a lipid emulsion (4 or 6 μmol/h of triolein). KO mice transported triacylglycerol (TG) as efficiently as WT mice when infused with the lower lipid dose; when infused with 6 μmol/h of triolein, however, KO mice transported significantly less TG to lymph than WT mice, leading to the accumulation of mucosal TG. Interestingly, the size of lipoprotein particles from both KO and WT mice were enlarged to chylomicron-size particles during absorption of the higher dose. These increased-size particles produced by KO mice were not associated with increased apo AIV secretion. However, we found that the gut of the KO mice secreted fewer apo B molecules to lymph (compared with WT), during both fasting and lipid infusion, leading us to conclude that the KO gut produced fewer numbers of TG-rich lipoproteins (including chylomicron) than the wild-type animals. The reduced apo B secretion in KO mice was not related to reduced microsomal triglyceride transfer protein lipid transfer activity. We propose that apo B48 is the preferred protein for the gut to coat chylomicrons to ensure efficient chylomicron formation and lipid absorption.
Gliadin-dependent neuromuscular and epithelial secretory responses in gluten-sensitive HLA-DQ8 transgenic mice
Authors: Verdu E. F. , Huang X. , Natividad J. , Lu J. , Blennerhassett P. A. , David C. S. , McKay D. M. , Murray J. A.
Published: November 2007

Celiac disease is a gluten intolerance caused by a T-cell response against human leukocyte antigen (HLA)-DQ2 and DQ8-bound gluten peptides. Some subjects experience gastrointestinal symptoms in the absence of villous atrophy. Here we investigate the potential mechanisms of gut dysfunction in gluten-sensitive HLA-DQ8 transgenic mice. HLA-DQ8 mice were sensitized and gavaged with gliadin 3×/wk for 3 wk (G/G). Controls included 1) nonsensitized mice gavaged with rice (C); 2) gliadin-sensitized mice gavaged with rice (G/R); and 3) BSA-sensitized mice gavaged with BSA (BSA/BSA). CD3+ intraepithelial lymphocyte, macrophage, and FOX-P3-positive cell counts were determined. Acetylcholine release, small intestinal contractility, and epithelial ion transport were measured. Gut function was investigated after gluten withdrawal and in HLA-DQ6 mice. Intestinal atrophy was not observed in G/G mice. Recruitment of intraepithelial lymphocyte, macrophages, and FOX-P3+ cells were observed in G/G, but not in C, G/R, or BSA/BSA mice. This was paralleled by increased acetylcholine release from the myenteric plexus, muscle hypercontractility, and increased active ion transport in G/G mice. Changes in muscle contractility normalized in DQ8 mice after a gluten withdrawal. HLA-DQ6 controls did not exhibit the abnormalities in gut function observed in DQ8 mice. Gluten sensitivity in HLA-DQ8 mice induces immune activation in the absence of intestinal atrophy. This is associated with cholinergic dysfunction and a prosecretory state that may lead to altered water movements and dysmotility. The results provide a mechanism by which gluten could induce gut dysfunction in patients with a genetic predisposition but without fully evolved celiac disease.
Longitudinal Study of Insulin-like Growth Factor, Insulin-like Growth Factor Binding Protein-3, and their Polymorphisms: Risk of Neoplastic Progression in Barrett's Esophagus
Authors: Siahpush Sid H. , Vaughan Thomas L. , Lampe Johanna N. , Freeman Robert , Lewis SKay , Odze Robert D. , Blount Patricia L. , Ayub Kamran , Rabinovitch Peter S. , Reid Brian J. , Chen Chu
Published: November 2007

Background: Insulin-like growth factor-I (IGF-I) is a potent mitogen. IGF-I and its main binding protein, IGF binding protein-3 (IGFBP-3), and their polymorphisms have been investigated in relation to risk of many cancers, but not esophageal adenocarcinoma.

Materials and Methods: We used data and specimens from a longitudinal study of persons with Barrett's esophagus (n = 344; median, 5.4 years follow up) to determine whether baseline serum concentrations of IGF-I and IGFBP-3 and associated polymorphisms were related to the risk of developing esophageal adenocarcinoma or flow cytometric abnormalities.

Results: Overall, circulating concentrations of IGF-I and IGBP-3 were not associated with risk of esophageal adenocarcinoma or flow cytometric abnormalities, with the exception of an approximate tripling of risk of aneuploidy among participants with higher IGFBP-3 levels [above median; adjusted hazard ratio (HR) comparing subjects with levels lower than median versus higher of equal to median, 2.7; 95% confidence interval (95% CI), 1.2-6.0; P = 0.01]. Genotypic analyses revealed that persons with the IGF-I [cytosine-adenine (CA)]19 or the IGFBP-3 A-202C C allele were associated with lower circulating concentrations of IGF-I (Ptrend = 0.01) and IGFBP-3 (Ptrend = 0.002), respectively. Persons with two copies of the IGF-I receptors 2-bp deletion allele had a nonsignificant 2-fold increased risk of tetraploidy (HR, 2.3; 95% CI, 0.9-5.9; Ptrend = 0.11). After adjustment for IGFBP-3 levels, participants carrying two IGFBP-3 C alleles had a significantly higher risk of developing aneuploidy (HR, 3.8; 95% CI, 1.0-14.0; Ptrend = 0.04) than carriers of A alleles; whereas no associations were observed between the outcomes studied and the IGF-I receptors AGG trinucleotide repeat polymorphism at position 97.

Conclusion: Our findings, although based on a relatively small number of outcomes and subject to several limitations, indicate a potential role of the complex IGF system in neoplastic progression among persons with Barrett's esophagus. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2387–96)
No Effect of Exercise on Colon Mucosal Prostaglandin Concentrations: A 12-Month Randomized Controlled Trial
Authors: Abrahamson Page E. , King Irena B. , Ulrich Cornelia M. , Rudolph Rebecca E. , Irwin Melinda L. , Yasui Yutaka , Surawicz Christina , Lampe Johanna W. , Lampe Paul D. , Morgan Angela , Sorensen Bess E. , Ayub Kamran , Potter John D. , McTiernan Anne
Published: November 2007

Background: Epidemiologic studies provide evidence that exercise is associated with reduced risk of colon cancer. Exercise may exert protective effects on the colon by influencing prostaglandin production. We hypothesized that an exercise intervention would decrease prostaglandin E2 concentrations and increase prostaglandin F2α in colon biopsies compared with controls.

Methods: A 12-month randomized controlled trial testing the effects of exercise on colon mucosal prostaglandin concentrations was conducted in men (n = 95) and women (n = 89). The exercise intervention included moderate-to-vigorous aerobic activity, 60 min/d, 6 days/wk versus controls. Prostaglandin E2 and F2α concentrations were measured in colon biopsies using an enzyme-linked immunoassay at baseline and at 12 months to assess changes in mean concentration for each group.

Results: Baseline colon prostaglandin E2 and F2α concentrations were not correlated with age, race, education, family history of colon cancer, previous polyps, body size, diet, smoking, nonsteroidal antiinflammatory drug use, metabolic factors, or sex hormone levels. For both men and women, the exercise and control groups showed no change in mean prostaglandin E2 or F2α between the baseline and 12-month biopsies. There was no difference in mean prostaglandin concentrations between exercisers and controls when exercisers were grouped by level of intervention adherence. Results were not modified by baseline age, body mass index, percentage of body fat, nonsteroidal antiinflammatory drug use, history of adenomatous polyps, or family history of colon cancer.

Conclusion: A 12-month moderate-to-vigorous intensity aerobic exercise intervention did not result in significant changes in colon mucosal prostaglandin concentrations. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2351–6)
Ataxia Telangiectasia-Mutated Gene Is a Possible Biomarker for Discrimination of Infiltrative Deep Penetrating Nevi and Metastatic Vertical Growth Phase Melanoma
Authors: Roesch Alexander , Becker Bernd , Bentink Stefan , Spang Rainer , Vogl Annegret , Hagen Ilja , Landthaler Michael , Vogt Thomas
Published: November 2007

The deep penetrating nevus (DPN) is a variant of benign melanocytic nevus with clinical and histologic features mimicking vertical growth phase, nodular malignant melanoma (NMM). Because fatal misdiagnosis such as NMM occurs in 29% to 40% of the DPN, molecular differentiation markers are highly desirable. Beyond the clinical demand for precise diagnosis and diagnosis-adapted, preventive therapeutic strategies, the DPN represents a valuable natural model for melanocytic invasion without metastatic potential that per se deserves further investigations. In the present study, at first, we used a genome-wide, microarray-based approach to systematically prescreen for possible molecular markers differentially expressed between selected cases of typical DPN (n = 4) and metastatic NMM controls (n = 4). Gene expression profiling was done on Affymetrix Human X3P microarrays. Of the 47,000 genes spotted, we identified a list of 227 transcripts, which remained significantly regulated at a false discovery rate of 5%. Subsequently, we verified the expression of a subset of the most interesting transcripts in a larger immunohistochemical series (DPN, n = 17; NMM, n = 16). Of these transcripts, three were selected for immunohistochemical confirmation: tissue inhibitor of metalloproteinase-2, tumor protein D52, and ataxia telangiectasia-mutated gene (ATM). Additional criteria for selection from the list of 227 significantly regulated transcripts were grouping into functional Ingenuity networks and a known melanoma- or cancer-relevant function. Following these criteria, we detected a highly significant up-regulation of ATM transcription in NMM, which was also mirrored by ATM protein up-regulation. In contrast to the other markers, ATM particularly might serve as a suitable diagnostic and reliable discriminator of DPN/NMM because ATM immunoreactivity also showed a reliable staining consistency within all samples of both entities. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2486–90)
Evaluation of the Association with Cervical Cancer of Polymorphisms in Syndecan-1, a Heparan Sulfate Proteoglycan Involved with Viral Cell Entry
Authors: Yu Kelly J. , Bashirova Arman , Madeleine Margaret M. , Cheng Jie , Johnson Lisa G. , Schwartz Stephen M. , Carrington Mary , Hildesheim Allan
Published: November 2007

Infection with 1 of ∼15 oncogenic human papillomaviruses is known to be linked to the development of all histologic forms of cervical cancer. We evaluated whether polymorphisms in syndecan-1 (SDC-1), a gene whose protein product is believed to be involved in human papillomavirus entry into epithelial cells, were associated with histologic subtypes of cervical cancer. A total of 293 in situ/invasive adenocarcinoma cases, 260 in situ/invasive squamous cell carcinoma cases, and 478 controls from two studies conducted in the Eastern United States and Seattle area were evaluated. DNA from peripheral blood was used for testing. We sequenced 5 exons and 60 nucleotides upstream of the start codon for SDC-1 in a random subset of 50 cases and 50 controls from the Eastern U.S. Study and identified two polymorphisms (E84E, rs2230924 and Pro-27 C → T, rs11544860). PCR-based testing was done to evaluate risk associated with these two polymorphisms. Polymorphisms of SDC-1 were not associated with risk of squamous cell carcinomas of the cervix. Similarly, there was no evidence for an association between SDC-1 exon 3 polymorphisms and risk of cervical adenocarcinomas. A marginally significant increase in risk of cervical adenocarcinoma was associated with the presence of the Pro-27 polymorphism (pooled odds ratios, 1.6; 95% confidence intervals, 0.99-2.6), an effect that was restricted to the Eastern U.S. Study. Our results indicate a lack of association between SDC-1 polymorphisms and risk of squamous cell carcinomas of the cervix. An association between SDC-1 Pro-27 polymorphism and cervical adenocarcinoma cannot be ruled out. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2504–8)
Nicotine and Carcinogen Exposure with Smoking of Progressively Reduced Nicotine Content Cigarette
Authors: Benowitz Neal L. , Hall Sharon M. , Stewart Susan , Wilson Margaret , Dempsey Delia , Jacob Peyton
Published: November 2007

Background: Reducing the nicotine content of cigarettes to make them non-addictive has been widely discussed as a potential strategy for tobacco regulation. A major concern with nicotine reduction is that smokers will compensate for reduced nicotine by smoking more cigarettes and/or smoking more intensively, thereby increasing their exposure to tobacco smoke toxins. This study examined whether gradual reduction in nicotine exposure increases exposure to tobacco smoke toxins.

Methods: This 10-week longitudinal study of 20 healthy smokers involved smoking their usual brand followed by different types of research cigarettes with progressively lower nicotine content, each smoked for 1 week. Subjects were followed for 4 weeks after returning to smoking their usual brand (or quitting). Smoking behaviors, chemical biomarkers of tobacco smoke exposure, and cardiovascular effect biomarkers were measured.

Findings: Intake of nicotine declined progressively as the nicotine content of cigarettes was reduced, with little evidence of compensation. Cigarette consumption and markers of exposure to carbon monoxide and polycyclic aromatic hydrocarbons, as well as cardiovascular biomarkers remained stable, whereas urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol excretion decreased. Twenty-five percent of participants had spontaneously quit smoking 4 weeks after completing the research cigarette taper.

Implications: Our findings with reduced nicotine content cigarettes differ from those of commercial low yields for which compensatory smoking for lower nicotine delivery is substantial. Our data suggest that the degree of nicotine dependence of smokers can be lowered without increasing their exposure to tobacco smoke toxins. Gradual reduction of nicotine content of cigarettes seems to be feasible and should be further evaluated as a national tobacco regulatory strategy. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2479–85)
BRCA1andBRCA2Mutations in an Asian Clinic-based Population Detected Using a Comprehensive Strategy
Authors: Ang Peter , Lim Irene H.K. , Lee Tze-Chuen , Luo Jie-Ting , Ong Danny C.T. , Tan Puay Hoon , Lee Ann S.G.
Published: November 2007

Background and objective: Genetic testing for germ line mutations in the BRCA1 and BRCA2 genes for some families at high risk for breast and/or ovarian cancer may yield negative results due to unidentified mutations or mutations with unknown clinical significance. We aimed to accurately determine the prevalence of mutations in these genes in an Asian clinic-based population by using a comprehensive testing strategy.

Materials and Methods: Ninety-four subjects from 90 families were accrued from risk assessment clinics. In addition to conventional mutational screening of BRCA1 and BRCA2, multiplex ligation-dependent probe amplification for the detection of large genomic rearrangements, evaluation of splice site alterations using transcript analysis and SpliceSiteFinder prediction, and analysis of missense mutations of unknown significance by multiple sequence alignment, PolyPhen analysis, and comparison of Protein Data Bank structures were incorporated into our testing strategy.

Results: The prevalence rates for clearly deleterious BRCA1 and BRCA2 mutations were 6.7% (6 of 90) and 8.9% (8 of 90), respectively, or 7.8% (7 of 90) and 11.1% (10 of 90), respectively, by including missense mutations predicted to be deleterious by computational analysis. In contrast to observations from European and American populations, deleterious mutations in BRCA2 (10 families) were more common than for BRCA1 (7 families). Overall, the frequency of mutations was 12.2% (n = 11) by conventional screening. However, by including deleterious mutations detected using multiplex ligation-dependent probe amplification (n = 1), transcript analysis (n = 2), and computational evaluation of missense mutations (n = 3), the frequency increased substantially to 18.9%. This suggests that the comprehensive strategy used is effective for identifying deleterious mutations in Asian individuals at high risk for breast and/or ovarian cancer. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2276–84)
Cholesterol-Lowering Drugs and Advanced Prostate Cancer Incidence in a Large U.S. Cohort
Authors: Jacobs Eric J. , Rodriguez Carmen , Bain Elizabeth B. , Wang Yiting , Thun Michael J. , Calle Eugenia E.
Published: November 2007

Background: 3-Hydroxy-3-methylglutaryl CoA reductase inhibitors, commonly known as statins, account for the great majority of cholesterol-lowering drug use in the United States. Long-duration statin use was associated with substantially reduced risk of advanced prostate cancer in a recent large prospective study.

Methods: We examined the association between use of cholesterol-lowering drugs and prostate cancer incidence by disease stage and grade among 55,454 men in the Cancer Prevention Study II Nutrition Cohort. Proportional hazards modeling was used to calculate RRs.

Results: During follow-up from 1997 to 2003, we identified 3,413 cases of incident prostate cancer, including 317 cases of advanced prostate cancer. After adjustment for age, history of prostate-specific antigen testing, and other potential prostate cancer risk factors, current use of cholesterol-lowering drugs for 5 or more years was not associated with overall prostate cancer incidence (multivariate adjusted rate ratio, 1.06; 95% confidence interval, 0.93-1.20), but was associated with a marginally statistically significant reduction in risk of advanced prostate cancer (rate ratio, 0.60; 95% confidence interval, 0.36-1.00).

Conclusion: These results provide some support for the hypothesis that long-term statin use is associated with reduced risk of advanced prostate cancer. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2213–7)
An International Case-Control Study of Interleukin-4Rα, Interleukin-13, and Cyclooxygenase-2 Polymorphisms and Glioblastoma Risk
Authors: Schwartzbaum Judith A. , Ahlbom Anders , Lönn Stefan , Malmer Beatrice , Wigertz Annette , Auvinen Anssi , Brookes Anthony J. , Collatz Christensen Helle , Henriksson Roger , Johansen Christoffer , Salminen Tina , Schoemaker Minouk J. , Swerdlow Anthony J. , Debinski Waldemar , Feychting Maria
Published: November 2007

Previous studies found that allergies are inversely related to risk of glioma. In an earlier publication, using data from a Swedish case-control study, Schwartzbaum et al. report an inverse relation between risk of glioblastoma and four single nucleotide polymorphisms (SNP) on two genes [interleukin (IL)-4Rα, IL-13] that are associated with allergies. In addition, recent studies suggest that IL-4 and IL-13 induce cyclooxygenase-2 (COX-2) to resolve brain inflammation. To see whether previous Swedish results (110 cases, 430 controls) would be replicated, we estimated the association between glioblastoma and two IL-4Rα (rs1805015, rs1801275) and two IL-13 (rs20541, rs1800925) SNPs and their haplotypes and one COX-2 SNP (−765GC) using additional English, Danish, and Finnish data (217 cases, 1,171 controls). Among general population controls, we evaluated associations between these haplotypes, the COX-2 SNP, and self-reported allergies. Our data did not support our original observations relating individual IL-4Rα, IL-13, or COX-2 SNPs to glioblastoma risk. However, the T-G IL-4Rα haplotype was associated with glioblastoma risk (odds ratio, 2.26; 95% confidence interval, 1.13-4.52) and there was a suggestion of an inverse relation between this haplotype and hayfever prevalence among controls (odds ratio, 0.38; 95% confidence interval, 0.14-1.03). The lack of support for a link between four IL-4Rα and IL-13 SNPs and glioblastoma may reflect the absence of associations or may result from uncontrolled confounding by haplotypes related both to those that we examined and glioblastoma. Nonetheless, the association between the T-G IL-4Rα haplotype and glioblastoma risk may indicate a role of immune factors in glioblastoma development. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2448–54)