bluuebunny/crossref_metadata_2025 huggingface dataset:
INHERITED SKILLS AND TECHNOLOGY: INDIAN ENTREPRENEURSHIP DEVELOPMENT
Authors: HEGDE GANESH S. , NARAHARI N. S.
Published: September 2009

Entrepreneurial development in India relies on generational mentoring, family business skill set, and exploration of technological progress. The know-how of skills, learned and refined over generations, leads to sustained development that is then converted into technology. Inheritance is one aspect that plays a major role in skill development. The transformation of skill into a technological component paves the way for the successful entrepreneurship. The spark initiated through inherited skill sets and ignited through the addition of technology results in useful entrepreneurial value. The basic societal needs remain the same while the trends take a changed form with the advent in technology. This requires the conversion of the time-honored skills through adaptation of the technological exponent in the changing societal trends. This paper offers an optimization model with maximization of entrepreneurial value as the objective and business output as the constraint. Skill and technology are taken as the variables. The model uses the primer value theorem as the computational tool, which solves the model in the indeterminate domain to suggest different strategies. The concept is demonstrated through three case examples.
DEMOCRACY AND THE ENVIRONMENT IN RUSSIA
Authors: KOVALEV NICOLE , KÖPPEL JOHANN , DROZDOV ALEXANDER , DITTRICH ECKHARDT
Published: September 2009

Since 1988, the Russian Federation has required that laws, plans, programs and all kind of projects undergo an environmental assessment. A mandatory component of the EIA in Russia is public participation. In this paper different case studies are used to find out to what extent public could influence environmental decision making processes from the early eighties until 2002. The cases selected include several where the public was passive or where it had limited activities, but also some where the participation was strong and projects were improved or stopped. As far as these case studies highlighted, the civil society in Russia can be described as an organized and sometimes strong factor in the approval process. The behaviour displayed by decision-makers, however, revealed at times a remarkable democratic deficit.
Effect of scenario on perceptual sensitivity to errors in animation
Authors: Reitsma Paul S. A. , O'Sullivan Carol
Published: September 2009

A deeper understanding of what makes animation perceptually plausible would benefit a number of applications, such as approximate collision detection and goal-directed animation. In a series of psychophysical experiments, we examine how measurements of perceptual sensitivity in realistic physical simulations compare to similar measurements done in more abstract settings. We find that participant tolerance for certain types of errors is significantly higher in a realistic snooker scenario than in the abstract test settings previously used to examine those errors. By contrast, we find tolerance for errors displayed in realistic but more neutral environments was not different from tolerance for those errors in abstract settings. Additionally, we examine the interaction of auditory and visual cues in determining participant sensitivity to spatiotemporal errors in rigid body collisions. We find that participants are predominantly affected by visual cues. Finally, we find that tolerance for spatial gaps during collision events is constant for a wide range of viewing angles if the effect of foreshortening and occlusion caused by the viewing angle is taken into account.
What is web science and why is it important to CSE
Authors: Hall Wendy
Published: September 2009

The World Wide Web has changed the world. It has changed the ways we communicate, collaborate, and educate. We increasingly live in a Web-dependent society in a Web-dependent world. The Web is also the largest human information construct and it is growing faster than any other system. However, it is a striking fact that there is no systematic discipline to study the Web. We need to understand the current, evolving, and potential Web but at the moment we have no means of predicting the impact that future developments in the Web will have on society or business. Web Science aims to anticipate these impacts. It is the study of the social behaviours in the Web at the inter-person, inter-organizational and societal level, the technologies that enable and support this behaviour, and the interactions between these technologies and behaviours. It is therefore inherently interdisciplinary and at even the simplest level represents a fundamental collaboration between computer science and the social sciences.

Computer Science as a discipline has not grasped the Web and the implications of its development. Most Computer Science departments do not teach "Web Science" fundamentals let alone specialist courses in this area, either with or without contributions from the social sciences or other relevant disciplines. This talk will explore the fundamentals of Web Science and make the case for Computer Science educators to meet this challenge head-on. Not only will it revitalise Computer Science degrees, it will also encourage the development of new degrees that we argue will attract a wider diversity and increasing number of students in the future.
Using accessible digital resources for teaching database design
Authors: Moreno Lourdes , Iglesias Ana M. , Castro Elena , Martinez Paloma
Published: September 2009

This paper introduces a pilot experience in teaching database using accessible digital resources in 3
er
course of Computer Science degree at Universidad Carlos III de Madrid. A platform containing learning material in different formats (video, audio, slides presentation) has been designed allowing students accessing resources as well as to be evaluated by means of tests. Preliminary results show that 46.81% of the students have already interacted with the system and 97.12% of the students passed the tests.
Teaching an object-oriented CS1 -
Authors: Goldwasser Michael H. , Letscher David
Published: September 2009

There is an ongoing debate regarding the role of object orientation in the introductory programming sequence. While the pendulum swings to and fro between the "objects first" and "back to basics" extremes, there is general agreement that object-oriented programming is central to modern software development and therefore integral to a computer science curriculum. Developing effective approaches to teach these principles raises challenges that have been exacerbated by the use of Java or C++ as the first instructional language.

In this paper, we recommend Python as an excellent choice for teaching an object-oriented CS1. Although often viewed as a "scripting" language, Python is a fully object-oriented language with a consistent object model and a rich set of built-in classes. Based upon our experiences, we describe aspects of the language that help support a balanced introduction to object orientation in CS1. We also discuss the downstream effects on our students' transition to Java and C++ in subsequent courses.
Assessment and comparison of local and global SW engineering practices in a classroom setting
Authors: Petkovic Dragutin , Thompson Gary D. , Todtenhoefer Rainer
Published: September 2009

In this paper we present assessment and comparison of local and global software (SW) engineering practices based on our software engineering (SE) class jointly taught for the last there years between San Francisco State University (SFSU) and the University of Applied Sciences, Fulda University, Germany. We define global SE practices as those used when the team members are for the most part distributed in terms of location and time, and hence do not meet regularly in person. While global SE practices have become a significant mode of SW development, surprisingly little formal measurements and comparisons have been done to understand it and compare it with traditional (local) SE practices. Moreover, the challenge remains as to how to effectively prepare students and employees for this environment. The key contribution of this paper is an attempt to objectively compare differences between local and global SW engineering practices from the developers' perspective, using measurements from our SFSU/Fulda SW engineering class as a simulation of a real-world environment. We also propose practical SE teamwork assessment methods based on our comparison measurements. In analyzing the differences between local and global SE practices we measure and analyze the following five main factors: quality of final delivery (including development of milestone documentation), progress impediment factors, expended effort, level of collaborative activity and teamwork problems. One of the surprising findings is that in today environment the differences between local and global SE practices are blurring, since local groups have to employ many practices of global groups, e.g. are teams of diverse cultures who seldom meet each other in person. We also confirm that global groups spend significantly more effort in producing comparable deliverables.
Assessing students' practice of professional values
Authors: Fuller Ursula , Keim Bob
Published: September 2009

This paper challenges the traditional approach to assessment in computing courses that restricts it to the cognitive domain and does not seek to measure attitudes and values. It identifies the role of professional values in the computing curriculum and presents examples of assessment related to some important professional characteristics. It then explores how assessment in the affective domain can help to improve our students' acquisition of professional values and constructive alignment between learning outcomes and assessment tasks. Finally, it considers the ethical issues raised by the assessment of values.
The "instructed-teacher"
Authors: Bower Matt
Published: September 2009

This paper describes a computer science specific pedagogical pattern that has emerged from conducting a three semester design-research project investigating teaching computing online. The "Instructed-Teacher" pedagogical pattern distinguished itself as an effective interactive strategy for eliciting and developing students' mental models. The pattern is presented and key observations regarding its implementation are shared. The teaching and research context is described in order to assist transferability and inform validity.
A distance learning approach to teaching eXtreme programming
Authors: Murphy Christian , Phung Dan , Kaiser Gail
Published: September 2009

As university-level distance learning programs become more and more popular, and software engineering courses incorporate eXtreme Programming (XP) into their curricula, certain challenges arise when teaching XP to students who are not physically co-located. In this paper, we present the results of a three-year study of such an online software engineering course targeted to graduate students, and describe some of the specific challenges faced, such as students' aversion to aspects of XP and difficulties in scheduling. We discuss our findings in terms of the course's educational objectives, and present suggestions to other educators who may face similar situations.
Learning through creating learning objects
Authors: Abad Cristina L.
Published: September 2009

An alternative to a final programming project in a Distributed Systems course is presented. The alternative project, which can easily be adapted to several Computer Science courses, consists in assigning different course topics to pairs of students, for them to develop an interactive learning object to help their classmates and future students of the class understand the subject. The project was well received by the students of the class, and their comments and survey results suggest that their knowledge on the subject improved both by using the learning objects of their peers and by working in developing their own.
Creativity as a pathway to computer science
Authors: Knobelsdorf Maria , Romeike Ralf
Published: September 2009

The study presented in this paper explores characteristics of creativity and the question whether creativity forms a possible pathway into the field of Computer Science (CS). For this purpose, we analyze computing experiences of students majoring in CS and Bioinformatics. The study is part of two research projects exploring creativity in CS Education and students' pathways to CS.
What are information technology's key qualifications?
Authors: Dörge Christina , Schulte Carsten
Published: September 2009

What kind of IT key qualifications do we have to teach in order to lessen the digital divide between educated and uneducated IT users, and to enable students who live in an IT-rich world to gain insights into the underlying science?

In this paper we argue that key qualifications, IT skills, and IT or media literacy can not be reduced to the teaching of applicational aspects, that is, to the functional characteristics of the IT systems in question. Instead, IT key qualifications consist in knowledge about the
concepts
of computer science.

Applying the concept of educational lenses (described in previous papers) to a course on IT key qualifications, we are able to obtain a more focused approach towards a definition of IT skills.
Enhancing the general background of CS students through a computing history course
Authors: Giangrandi Paolo , Mirolo Claudio
Published: September 2009

The Italian Association of Automatic Computing (AICA) promotes the introduction of academic courses on the computing history. Also the University of Udine participates in this project by offering an elective course in the CS and IT programs. After the first two years of this new experience, we attempt to outline what is emerging from the analysis of the students' answers to a couple of specifically designed questionnaires and to the examination tests. A major point of interest is that the course helps us to get some insight on our students' general background and attitude toward culture. In particular, the first observations seem to indicate that they are rather curious about the technological artifacts, but come with a poor historical picture and then have difficulty putting science and technology in a historical perspective. Although our analysis reveals some positive trends, it is not easy to assess the course effectiveness in this respect because of the lack of suitable benchmarks.
Using eclipse in the classroom
Authors: Deugo Dwight
Published: September 2009

In this Tips & Techniques session, I will describe what to teach students about Eclipse, while remaining in the contexts of existing courses, such as CS1/CS2, in higher-level courses such as Quality Assurance, and in project courses.
Scrambling for students
Authors: Young Alison , Pears Arnold , Anasagasti Pedro de Miguel , Romeike Ralf , Goldweber Michael , Goldwasser Michael , Almstrum Vicki
Published: September 2009

Teams representing the USA and Europe engage in a battle of words and wits to establish "once and for all" which educational system produces the superior outcome. This "no holds barred" debate leaves no stone unturned in a search for truth on this question, providing a final answer to a controversy that has plagued our community since the inception of computing itself. Witness this historic moment in the history of CS education first hand!
Computing research methods multi-perspective digital library
Authors: Applin Anne G. , Holz Hilary J.
Published: September 2009

For the past three years, SIGCSE has sponsored a design research project on teaching Computing Research Methods (CRM) [4]. The initial phase of the work included an ITiCSE working group that gathered a great deal of literature on and about: computing research; CRM; and teaching CRM [3]. During the literature review, we discovered a number of similar current and prior efforts, some of which had even met with limited success within their discourse community. However, because the CRM literature is divided across publishers, indices, and discourse communities, none of the earlier efforts established the common ground necessary for meaningful dialog on curricular issues (see section 1.1. of [1])

To establish that common ground, we decided to foster a
scholar-produced digital resource
to facilitate integrating teaching / learning research methods across the computing curriculum [1]. Scholar-produced digital resources are digital libraries that are produced by scholarly communities of practice, rather than by external stakeholders such as commercial publishers or libraries. These digital libraries are rich interactive web locales that ". . . include aggregations of resources that support research, such as field-based topic gateways and bibliographies; products of original research such as novel multimedia publications and handbook type web publications, communication forums such as preprint archives and pure e-journals; and research tools such as non-proprietary software available via the web." [2]

We started work on the CRM Multi-Perspective Digital Library (CRM-MPDL) in early 2007. A second ITiCSE working group [1] focused on the faculty perspectives in CRM-MPDL. A SIGCSE special projects grant funded student research assistants for CRM-MPDL. As a consequence, students have become a very active and vocal constituency in the project, and they have made significant progress on a set of student design and content elements for CRM-MPDL.

To date, we have developed an international participatory design community [4]; conducted and published an extensive literature review and glossary [3]; developed some initial curricular materials [4]; and constructed a prototype design for the faculty perspective in a multiperspective digital resource to integrate teaching research methods across the computing curriculum [1].

One of the goals of the project has been to build a tool that is useful to faculty, students, industry, administrators, and anyone else who is interested in teaching or learning about CRM. A prototype of CRM-MPDL is ready to be tested, interacted with, and critiqued. The goal of this poster is to solicit participation from the ITiCSE conference attendees. An international audience is necessary for us to get the most comprehensive feedback for the tool. We have a growing set of content materials and a growing set of design materials. A laptop will be available at the poster for attendees to experience CRM-MPDL on site.
Learning object oriented programming
Authors: Burrell Christopher J.
Published: September 2009

Constructing new knowledge when learning to program is acknowledged as a difficult process. This poster displays visual models constructed from pre-course questionnaires and the activities and programs produced by novices when taking the first steps in programming. Case study and experimental methods were used to develop these individualized, "student learning models" in an attempt to identify and understand individual differences. A micro-world environment was developed to capture data associated with writing and running programs. Visualizations derived display the resulting learner models which can assist in understanding the developing knowledge state of individuals with the potential of providing a contribution to tutorial support.
A computer-based test to raise awareness of disability issues
Authors: Gray John , Harrison Gill , Gorra Andrea , Sheridan-Ross Jakki , Finlay Janet
Published: September 2009

The purpose of this poster is to share our experience of a staff development tool that has been developed to raise awareness amongst staff about issues that students with disabilities might face. A computer-based test has been created as a training tool to raise awareness among university academic staff of some common experiences faced by people with visual, mobility, hearing and cognitive difficulties when using a computer [1]. The development team is based at Leeds Metropolitan University and is part of a UK centrally-funded "Centre for Excellence in Teaching and Learning" (CETL) [2], in collaboration with the Universities of Durham, Newcastle and Leeds. The Centre is devoted to promoting "Active Learning in Computing" (ALiC) [3] and is the only CETL within the Computer Science academic area. This test simulates experiences of disabled students who use computers and take computer-based tests, and provides advice and guidance to university teaching staff on how they may best cater for the needs of such students. The poster presents the reasons for creating such a tool in such a format, its structure and content.
Teaching query writing
Authors: Hollingsworth Joseph E.
Published: September 2009

This paper is intended for those instructors asked to teach an undergraduate introductory class on SQL query writing, which is usually difficult for students to learn. After reading Bruer's
Schools for Thought
[1], we realized that we need to modify our approach so that it uses
informed
instruction (instead of traditional instruction) and since have noticed improvements in student performance in SQL query writing.
Learning for mastery in an introductory programming course
Authors: Jacková Jana
Published: September 2009

Teachers always look for new ways to make their teaching more effective. "The data show that mastery learning programs have positive effects on student achievement" [1]. We introduce work in progress of an educational research of teaching/learning (T/L) effectiveness in case the Mastery Learning (ML) approach is used in an introductory course of programming.
Analysis of ABET accreditation as a software process
Authors: Leach Ronald J.
Published: September 2009

The ABET assessment process is highly complex and is emphasizes the use of assessment to improve programs. Since the process is complex, it has a considerable overhead. This paper will present some models for estimating the added overhead of such assessment. The models can be used to help determine if any other activities must be curtailed because of the increased overhead of assessment. The models suggest which categories of colleges and universities will be affected most adversely by the overhead of the ABET accreditation process.
Students' perceptions of python as a first programming language at wits
Authors: Sanders Ian D. , Langford Sasha
Published: September 2009

The first year curriculum at the University of the Witwatersrand (Wits) is a breadth-first curriculum where students are introduced to a variety of topics in Computer Science (see Sanders and Mueller [5] for details). As part of the course the students are expected to come to terms with a number of basic algorithms and data structures which they are required to implement. When the curriculum was designed we chose Scheme as the implementation language. One reason for doing so was because the main entrance requirement for our course is a solid mathematics background as evidenced by good marks at school level. Our students thus have a good understanding of functions and we felt that Scheme?s functional style would make it accessible to all of our students. Another reason for choosing Scheme was because it is a language which would be new to all of our students.

Scheme was well received by those students who had never programmed before and proved to be a good language for meeting our teaching objectives but there was resistance to the language from the students who could already program as they considered it a waste of time to learn a language which was not (as they believed) used in the real world [3]. In addition, the use of Scheme did not really reduce the performance gap between the students with and without prior programming experience [2].

Python has been found to be a good first language for both experienced and inexperienced users [4] and its simple syntax and support of different programming paradigms seemed to make it an attractive option for our first year course. We believed that using Python would still allow us to meet our educational objectives ? it would be easily accessible to those students who had never programmed before and would support our approach of formulating algorithms Python has been found to be a good first language for both experienced and inexperienced users [4] and its simple syntax and support of different programming paradigms seemed to make it an attractive option for our first year course. We believed that using Python would still allow us to meet our educational objectives ? it would be easily accessible to those students who had never programmed before and would support our approach of formulating algorithms

In late 2007 we did a survey to assess the first year students? impressions of Python. The students were asked to indicate agreement, disagreement or neutrality to a number of questions about the use of Python. 55 students completed the survey ? 27 of these had no prior programming experience and 28 had programmed before. The Wilcoxon signed rank test was used to test the hypotheses that both groups believed that Python was a good first year language. The results show strong evidence that the students feel that Python is a suitable language. There are. however, still some students with prior programming experience who are resistant to new languages.
Multidisciplinary projects for first year engineering courses
Authors: Escribano Carmen , Giraldo Antonio , Mata Águeda , Sastre María Asunción
Published: September 2009

In this work we will expose some proposals directed to the development of horizontal skills in the first year courses of Mathematics for Computer Science, with the purpose of stimulating the curiosity and the interest of the students by means of collaborative work. Our experience is based on the planning of multidisciplinary activities following projects based learning (PBL) pedagogies, included in the joint educational planning of the mathematics courses in first year of Computer Science.
Simulation-based analysis of keyword auctions
Authors: Vorobeychik Yevgeniy
Published: September 2009

Keyword auctions account for an enormous proportion of revenue for the major search engines. Consequently, substantial literature analyzing alternative auction designs has sprouted in recent years. We contribute to this growing literature by engaging in a simulation-based analysis of strategic interactions in keyword auctions which are difficult to analyze in closed form. In this letter we provide an overview of two specific efforts in this direction. The first effort presents analysis of the dynamic bidding strategies, while the second effort is performed in a static context, but involves a close analysis of several classes of Bayesian bidding strategies. Both these efforts attempt to bridge the gap between the mostly theoretical literature to date and real auctions.
Airflow and Particle Transport in the Human Respiratory System
Authors: Kleinstreuer C. , Zhang Z.
Published: September 2009

Airflows in the nasal cavities and oral airways are rather complex, possibly featuring a transition to turbulent jet-like flow, recirculating flow, Dean's flow, vortical flows, large pressure drops, prevailing secondary flows, and merging streams in the case of exhalation. Such complex flows propagate subsequently into the tracheobronchial airways. The underlying assumptions for particle transport and deposition are that the aerosols are spherical, noninteracting, and monodisperse and deposit upon contact with the airway surface. Such dilute particle suspensions are typically modeled with the Euler-Lagrange approach for micron particles and in the Euler-Euler framework for nanoparticles. Micron particles deposit nonuniformly with very high concentrations at some local sites (e.g., carinal ridges of large bronchial airways). In contrast, nanomaterial almost coats the airway surfaces, which has implications of detrimental health effects in the case of inhaled toxic nanoparticles. Geometric airway features, as well as histories of airflow fields and particle distributions, may significantly affect particle deposition.
Genetic Consequences of Range Expansions
Authors: Excoffier Laurent , Foll Matthieu , Petit Rémy J.
Published: September 2009

Although range expansions have occurred recurrently in the history of most species, their genetic consequences have been little investigated. Theoretical studies show that range expansions are quite different from pure demographic expansions and that the extent of recent gene flow conditions expected patterns of molecular diversity within and between populations. Spatially explicit simulation studies have led to unexpected and fascinating results about genetic patterns emerging after a range expansion. For instance, spatial expansions can generate allele frequency gradients, promote the surfing of rare variants into newly occupied territories, induce the structuring of newly colonized areas into distinct sectors of low genetic diversity, or lead to massive introgression of local genes into the genome of an invading species. Interestingly, most of these patterns had been previously attributed to distinct selective processes, showing that taking into account the dynamic nature of a species range can lead to a paradigm shift in our perception of evolutionary processes.
Effect of hyperinsulinemia and very-low-calorie diet on interstitial cytokine levels in subcutaneous adipose tissue of obese women
Authors: Siklova-Vitkova Michaela , Polak Jan , Klimcakova Eva , Vrzalova Jindra , Hejnova Jindra , Kovacikova Michaela , Kovacova Zuzana , Bajzova Magda , Rossmeislova Lenka , Hnevkovska Zuzana , Langin Dominique , Stich Vladimir
Published: September 2009

Type 2 diabetes and obesity are associated with an enhanced release of a number of adipocytokines. Hyperinsulinemia, frequently present in type 2 diabetes and obesity, might be one of the drivers of the enhanced production of adipocytokines. The aim of this study was to investigate the interstitial levels of cytokines in subcutaneous adipose tissue (SCAT) in response to hyperinsulinemia and the effect of weight-reducing hypocaloric diet on this regulation in obese subjects. Thirteen obese premenopausal women participated in the study. Concentrations of seven cytokines were measured in plasma and in AT interstitial fluid collected by microdialysis during a euglycemic-hyperinsulinemic clamp and during control infusion of physiological saline. A subgroup of six women underwent a 4-wk very-low-calorie diet (VLCD). Microdialysis during the clamp was performed before and at the end of VLCD. Hyperinsulinemia induced an increase of monocyte chemoatractant protein (MCP-1) and IL-6 SCAT interstitial and plasma levels and elevated IL-8 levels in SCAT. The relative changes of IL-6 levels in the dialysate correlated with changes of IL-8 and MCP-1. The interstitial and plasma levels of IL-1β, IL-10, TNFα, and plasminogen activator inhibitor (PAI-1) remained unchanged in response to hyperinsulinemia. VLCD resulted in enhancement of the hyperinsulinemia-induced augmentation of MCP-1, IL-6, and IL-8 interstitial levels. In conclusion, hyperinsulinemia upregulates the interstitial levels of MCP-1, IL-6, and IL-8 in SCAT in obese women, whereas it does not affect IL-1β, IL-10, TNFα, and PAI-1 levels. Hypocaloric diet associated with weight reduction enhances the hyperinsulinemia-induced upregulation of MCP-1, IL-6, and IL-8 in SCAT.
Effects of the cannabinoid CB1 antagonist rimonabant on hepatic mitochondrial function in rats fed a high-fat diet
Authors: Flamment Mélissa , Gueguen Naïg , Wetterwald Céline , Simard Gilles , Malthièry Yves , Ducluzeau Pierre-Henri
Published: September 2009

The aim of this study was to investigate the effect of rimonabant treatment on hepatic mitochondrial function in rats fed a high-fat diet. Sprague-Dawley rats fed a high-fat diet (35% lard) for 13 wk were treated with rimonabant (10 mg·kg−1·day−1) during the last 3 wk and matched with pair-fed controls. Oxygen consumption with various substrates, mitochondrial enzyme activities on isolated liver mitochondria, and mitochondrial DNA quantity were determined. Body weight and fat mass were decreased in rats treated with rimonabant compared with pair-fed controls. Moreover, the serum adiponectin level was increased with rimonabant. Hepatic triglyceride content was increased, while serum triglycerides were decreased. An increase of mitochondrial respiration was observed in rats treated with rimonabant. The increase of mitochondrial respiration with palmitoyl-CoA compared with respiration with palmitoyl-l-carnitine stating that the entry of fatty acids into mitochondria via carnitine palmitoyltransferase I was increased in rats treated with rimonabant. Moreover, rimonabant treatment led to a reduction in the enzymatic activity of ATP synthase, whereas the quantity of mitochondrial DNA and the activity of citrate synthase remained unchanged. To summarize, rimonabant treatment leads to an improvement of hepatic mitochondrial function by increasing substrate oxidation and fatty acid entry into mitochondria for the β-oxidation pathway and by increasing proton leak. However, this increase of mitochondrial oxidation is regulated by a decrease of ATP synthase activity in order to have only ATP required for the cell function.
The 5-Lipoxygenase as a Common Pathway for Pathological Brain and Vascular Aging
Authors: Chu Jin , Praticò Domenico
Published: September 2009

Epidemiological studies indicate age as a strong risk factor for developing cardiovascular and neurodegenerative diseases. During the aging process, changes in the expression of particular genes can influence the susceptibility to these diseases. 5-Lipoxygenase (5-LO) by oxidizing fatty acids forms leukotrienes, potent mediators of oxidative and inflammatory reactions, two key pathogenic events in both clinical settings. This enzyme is widely distributed in the cardiovascular as well as in the central nervous system, where its expression levels increase with age, suggesting that it may be involved in their diseases of aging. The central theme of this article is that during aging, 5-LO acts as biologic link between different stressors and the development of cardiovascular and neurodegenerative diseases. We hypothesize that the age-dependent upregulation of 5-LO represents a “priming” factor in the vasculature as well as in the brain, where a subsequent exposure to triggering stimuli (i.e., infections) leads to an abnormal chronic inflammatory reaction, and ultimately results in increased organ vulnerability and functional deficits.
Adaptive Packet-Level Interleaved FEC for Wireless Priority-Encoded Video Streaming
Authors: Razavi Rouzbeh , Fleury Martin , Ghanbari Mohammed
Published: September 2009

Packet-level Forward Error Control (FEC) for video streaming over a wireless network has received comparatively limited investigation, because of the delay introduced by the need to assemble a group of packets. However, packet-level interleaving when combined with FEC presents a remedy to time-correlated error bursts, though it can further increase delay if this issue is not addressed. This paper proposes adapting the overall degree of interleaved packet-level FEC according to the display deadlines of packets, transmit buffer occupation, and estimated video input to the wireless channel, all of which address the issue of delay. To guard against estimation error, the scheme applies a conservative adaptation policy, which accounts for picture type importance to ensure that display deadlines are met, thus avoiding this defect of interleaving. The paper additionally introduces a greedy algorithm that effectively groups packet-level FEC protection according to packet priority. Priority encoding adds extra protection during deep fades. As feedback is not required, the interleaving scheme is suitable for all forms of video broadcast. A Bluetooth piconet demonstrates the packet-level FEC interleaving scheme, which provides higher quality delivered video compared to the industry-standard Pro-MPEG Cop#3r2 interleaving scheme.
Parathyroid Hormone–Related Protein Protects against Mammary Tumor Emergence and Is Associated with Monocyte Infiltration in Ductal Carcinoma In situ
Authors: Fleming Nicholas I. , Trivett Melanie K. , George Joshy , Slavin John L. , Murray William K. , Moseley Jane M. , Anderson Robin L. , Thomas David M.
Published: September 2009

Parathyroid hormone–related protein (PTHrP) is required for mammary gland development and promotes the growth of breast cancer metastases within bone. However, there are conflicting reports of the prognostic significance of its expression in primary breast cancers. To study the role of PTHrP in early breast cancer, the effect of conditional deletion of PTHrP was examined in the context of neu-induced mammary tumorigenesis. Loss of PTHrP resulted in a higher tumor incidence. Transcriptional profiling of the tumors revealed that PTHrP influenced genes relevant to heterotypic cell signaling, including regulators of monocyte recruitment. Immunohistochemical analysis of human breast cancers revealed that PTHrP expression was associated with both HER-2/neu expression and macrophage infiltration in preinvasive ductal carcinoma in situ. The gene expression signature associated with loss of PTHrP expression in vivo correlated with poorer outcome in human breast cancer. Together, these data indicate that loss of PTHrP accelerates mammary tumorigenesis possibly by a non–cell-autonomous tumor suppressor pathway. [Cancer Res 2009;69(18):7473–9]
The Multifaceted Role of MTDH/AEG-1 in Cancer Progression
Authors: Hu Guohong , Wei Yong , Kang Yibin
Published: September 2009

Cancer is the result of the progressive acquisition of multiple malignant traits through the accumulation of genetic or epigenetic alterations. Recent studies have established a functional role of MTDH (Metadherin)/AEG-1 (Astrocyte Elevated Gene 1) in several crucial aspects of tumor progression, including transformation, evasion of apoptosis, invasion, metastasis, and chemoresistance. Overexpression of MTDH/AEG-1 is frequently observed in melanoma, glioma, neuroblastoma, and carcinomas of breast, prostate, liver, and esophagus and is correlated with poor clinical outcomes. MTDH/AEG-1 functions as a downstream mediator of the transforming activity of oncogenic Ha-Ras and c-Myc. Furthermore, MTDH/AEG-1 overexpression activates the PI3K/Akt, nuclear factor κB (NFκB), and Wnt/β-catenin signaling pathways to stimulate proliferation, invasion, cell survival, and chemoresistance. The lung-homing domain of MTDH/AEG-1 also mediates the adhesion of tumor cells to the vasculature of distant organs and promotes metastasis. These findings suggest that therapeutic targeting of MTDH/AEG-1 may simultaneously suppress tumor growth, block metastasis, and enhance the efficacy of chemotherapeutic treatments. (Clin Cancer Res 2009;15(18):5615–20)
Candidate Biomarkers of Response to an Experimental Cancer Drug Identified through a Large-scale RNA Interference Genetic Screen
Authors: Mullenders Jasper , von der Saal Wolfgang , van Dongen Miranda M.W. , Reiff Ulrike , van Willigen Rogier , Beijersbergen Roderick L. , Tiefenthaler Georg , Klein Christian , Bernards René
Published: September 2009

Purpose: A major impediment in the optimal selection of cancer patients for the most effective therapy is the lack of suitable biomarkers that foretell the response of a patient to a given drug. In the present study, we have used large-scale RNA interference–based genetic screens to find candidate biomarkers of resistance to a new acyl sulfonamide derivative, R3200. This compound inhibits the proliferation of tumor cells in vitro and in vivo, but its mechanism of action is unknown.

Experimental Design: We used a large-scale RNA interference genetic screen to identify modulators of the efficacy of R3200. We searched for genes whose suppression in an in vitro cell system could cause resistance to the anticancer effects of R3200.

Results: We report here that knockdown of either RBX1 or DDB1 causes resistance to the anticancer effects of R3200, raising the possibility that these two genes may have utility as biomarkers of response to this drug in a clinical setting. Interestingly, both RBX1 and DDB1 are part of an E3 ubiquitin ligase complex.

Conclusions: We propose that suppression of the activity of a RBX1 and DDB1-containing E3 ligase complex leads to the stabilization of certain proteins, the increased abundance of which is in turn responsible for resistance to R3200. Moreover, our data suggest that RBX1 and DDB1 could potentially be developed into biomarkers of resistance to acyl sulfonamide–based cancer drugs. This will require clinical validation in a series of patients treated with R3200. (Clin Cancer Res 2009;15(18):5811–9)
Low p27 Expression Predicts Early Relapse and Death in Postmenopausal Hormone Receptor–Positive Breast Cancer Patients Receiving Adjuvant Tamoxifen Therapy
Authors: Filipits Martin , Rudas Margaretha , Heinzl Harald , Jakesz Raimund , Kubista Ernst , Lax Sigurd , Schippinger Walter , Dietze Otto , Greil Richard , Stiglbauer Wolfgang , Kwasny Werner , Nader Alexander , Stierer Michael , Gnant Michael F.X. ,   for the Austrian Breast and Colorectal Cancer Study Group
Published: September 2009

Purpose: Previously, we have shown that p27 may be a potential predictive biomarker for the selection of premenopausal women with early-stage hormone-responsive breast cancer for adjuvant endocrine therapy. The purpose of the present study was to assess the clinical relevance of p27 expression in postmenopausal hormone receptor–positive breast cancer patients who were treated with adjuvant tamoxifen therapy.

Experimental Design: We determined the expression of p27 by immunohistochemistry in the surgical specimens of breast carcinoma patients who had been enrolled in Austrian Breast and Colorectal Cancer Study Group Trial 06 and received tamoxifen for 5 years. Early relapse and death within the first 5 years of follow-up were analyzed using Cox models adjusted for clinical and pathologic factors.

Results: p27 expression was high (>70% p27-positive tumor cells) in 252 of 483 (52%) tumor specimens and was associated with favorable outcome of the patients. Women with high p27 expression had a significantly longer disease-free survival (adjusted hazard ratio for relapse, 0.22; 95% confidence interval, 0.11-0.42; P < 0.001) and overall survival (adjusted hazard ratio for death, 0.39; 95% confidence interval, 0.21-0.72; P = 0.002) as compared with women with low p27 expression.

Conclusion: Low p27 expression independently predicts early relapse and death in postmenopausal women with early-stage, hormone receptor–positive breast cancer who received adjuvant tamoxifen for 5 years. (Clin Cancer Res 2009;15(18):5888–94)
An allosteric kinase inhibitor binds the p21-activated kinase autoregulatory domain covalently
Authors: Viaud Julien , Peterson Jeffrey R.
Published: September 2009

Kinases are important therapeutic targets in oncology due to their frequent deregulation in cancer. Typical ATP-competitive kinase inhibitors, however, also inhibit off-target kinases that could lead to drug toxicity. Allosteric inhibitors represent an alternative approach to achieve greater kinase selectivity, although examples of such compounds are few. Here, we elucidate the mechanism of action of IPA-3, an allosteric inhibitor of Pak kinase activation. We show that IPA-3 binds covalently to the Pak1 regulatory domain and prevents binding to the upstream activator Cdc42. Preactivated Pak1, however, is neither inhibited nor bound significantly by IPA-3, demonstrating exquisite conformational specificity of the interaction. Using radiolabeled IPA-3, we show that inhibitor binding is specific and reversible in reducing environments. Finally, cell experiments using IPA-3 implicate Pak1 in phorbol-ester–stimulated membrane ruffling. This study reveals a novel allosteric mechanism for kinase inhibition through covalent targeting of a regulatory domain. [Mol Cancer Ther 2009;8(9):2559–65]
Correcting miR-15a/16 genetic defect in New Zealand Black mouse model of CLL enhances drug sensitivity
Authors: Salerno Erica , Scaglione Brian J. , Coffman Frederick D. , Brown Brian D. , Baccarini Alessia , Fernandes Helen , Marti Gerald , Raveche Elizabeth S.
Published: September 2009

Alterations in the human 13q14 genomic region containing microRNAs mir-15a and mir-16-1 are present in most human chronic lymphocytic leukemia (CLL). We have previously found the development of CLL in the New Zealand Black murine model to be associated with a point mutation in the primary mir-15a/16-1 region, which correlated with a decrease in mature miR-16 and miR-15a levels. In this study, addition of exogenous miR-15a and miR-16 led to an accumulation of cells in G1 in non–New Zealand Black B cell and New Zealand Black–derived malignant B-1 cell lines. However, the New Zealand Black line had significantly greater G1 accumulation, suggesting a restoration of cell cycle control upon exogenous miR-15a/16 addition. Our experiments showed a reduction in protein levels of cyclin D1, a miR-15a/16 target and cell cycle regulator of G1/S transition, in the New Zealand Black cell line following miR-15a/16 addition. These microRNAs were shown to directly target the cyclin D1 3′ untranslated region using a green fluorescent protein lentiviral expression system. miR-16 was also shown to augment apoptosis induction by nutlin, a mouse double minute 2 (MDM2) antagonist, and genistein, a tyrosine kinase inhibitor, when added to a B-1 cell line derived from multiple in vivo passages of malignant B-1 cells from New Zealand Black mice with CLL. miR-16 synergized with nutlin and genistein to induce apoptosis. Our data support a role for the mir-15a/16-1 cluster in cell cycle regulation and suggest that these mature microRNAs in both the New Zealand Black model and human CLL may be targets for therapeutic efficacy in this disease. [Mol Cancer Ther 2009;8(9):2684–92]
Inhibition of type I histone deacetylase increases resistance of checkpoint-deficient cells to genotoxic agents through mitotic delay
Authors: Alao John P. , Olesch Jeanette , Sunnerhagen Per
Published: September 2009

Histone deacetylase (HDAC) inhibitors potently inhibit tumor growth and are currently being evaluated for their efficacy as chemosensitizers and radiosensitizers. This efficacy is likely to be limited by the fact that HDAC inhibitors also induce cell cycle arrest. Deletion of the class I HDAC Rpd3 has been shown to specifically suppress the sensitivity of Saccharomyces cerevisiae DNA damage checkpoint mutants to UV and hydroxyurea. We show that in the fission yeast Schizosaccharomyces pombe, inhibition of the homologous class I HDAC specifically suppresses the DNA damage sensitivity of checkpoint mutants. Importantly, the prototype HDAC inhibitor Trichostatin A also suppressed the sensitivity of DNA damage checkpoint but not of DNA repair mutants to UV and HU. TSA suppressed DNA damage activity independently of the mitogen-activated protein kinase–dependent and spindle checkpoint pathways. We show that TSA delays progression into mitosis and propose that this is the main mechanism for suppression of the DNA damage sensitivity of S. pombe checkpoint mutants, partially compensating for the loss of the G2 checkpoint pathway. Our studies also show that the ability of HDAC inhibitors to suppress DNA damage sensitivity is not species specific. Class I HDACs are the major target of HDAC inhibitors and cancer cells are often defective in checkpoint activation. Effective use of these agents as chemosensitizers and radiosensitizers may require specific treatment schedules that circumvent their inhibition of cell cycle progression. [Mol Cancer Ther 2009;8(9):2606–15]