bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in Students’ Explanations for Gender Differences after Taking a Psychology of Women Class: More Constructionist and Less Essentialist
Authors: Yoder Janice D. , Fischer Ann R. , Kahn Arnold S. , Groden Jessica
Published: December 2007

We explored how students’ endorsements of essential (biological and personality) and constructed (socialization and contextual) explanations for gender differences changed from the start to the end of Psychology of Women (POW) classes along with their feminist attitudes. Results from surveys of 120 POW students from three universities indicated that these students began class with more feminist awareness, immersion, and constructionist thinking than 228 general students, and that constructionist thinking was associated with perceptions that gender differences can be eliminated. Students’ essentialism declined across their POW class, whereas their constructionist thinking increased and their feminist attitudes strengthened. End-of-semester feminist identification was associated with stronger endorsement of contextual explanations for gender differences above and beyond initial identification. We discuss implications for researchers, instructors, and activists.
Raising Male Privilege Awareness and Reducing Sexism: An Evaluation of Diversity Courses
Authors: Case Kim A.
Published: December 2007

Research examining the impact of women's studies courses provides evidence of student changes such as greater agreement with feminist and egalitarian attitudes, lower prejudice against women, and increased activism. Using a pre- and posttest design, the current studies assess students’ awareness of male privilege, prejudice against women, support for affirmative action, and identification as feminist following courses with and without gender content. In Study 1, students taking a course entitled Psychology of Race and Gender completed identical surveys during the first and last weeks of the semester. Study 2 included students in Psychology of Women, Introduction to Women's Studies, and courses not addressing gender. Participants in diversity and women's studies courses in both studies exhibited more male privilege awareness and support for affirmative action at the end of the semester compared to pretest. However, the change in women's studies students’ support for affirmative action and sexism levels was not significantly different from students in comparison courses. Women's studies students completed their courses with greater self-identification with feminism in contrast to non–women's studies students.
Geographies of business education: MBA programmes, reflexive business schools and the cultural circuit of capital
Authors: Hall Sarah
Published: December 2007

MBA programmes and the business schools that teach them have been identified by geographers and social scientists as central actors in the dissemination of economic and management theories into practice through concepts such as the cultural circuit of capital. However, the ways in which the exigencies of economic practice impact upon these actors within the cultural circuit of capital has received less attention. In response, this paper draws on research conducted into the teaching and learning of corporate valuation techniques in leading MBA programmes and their use in corporate finance practice in London to consider how the (re)production of economic theories in practice impacts upon the institutional and pedagogical strategies of leading business schools. I combine work in geography on the spatialities of economic knowledge with debates amongst management theorists surrounding the future of business schools to identify the importance of embodied expertise in the (re)production of financial theory in practice. These skills have a relatively ‘sticky’ geography, typically being best learnt in practice rather than in MBA classrooms. I argue that business schools are responding by rendering themselves materially and discursively ‘mobile’ at both the MBA curricula and institutional level, adopting a range of initiatives aimed at (re)positioning themselves closer to economic practice. In so doing, I develop conceptual understandings of the ‘circular’ nature of the cultural circuit of capital as well as calling for business schools, and the broader business education sector, to be a more central topic of geographical inquiry.
The Use of Linear Instrumental Variables Methods in Health Services Research and Health Economics: A Cautionary Note
Authors: Terza Joseph V. , Bradford W. David , Dismuke Clara E.
Published: December 2007

Objective.To investigate potential bias in the use of the conventional linear instrumental variables (IV) method for the estimation of causal effects in inherently nonlinear regression settings.

Data Sources.Smoking Supplement to the 1979 National Health Interview Survey, National Longitudinal Alcohol Epidemiologic Survey, and simulated data.

Study Design.Potential bias from the use of the linear IV method in nonlinear models is assessed via simulation studies and real world data analyses in two commonly encountered regression setting: (1) models with a nonnegative outcome (e.g., a count) and a continuous endogenous regressor; and (2) models with a binary outcome and a binary endogenous regressor.

Principle Findings.The simulation analyses show that substantial bias in the estimation of causal effects can result from applying the conventional IV method in inherently nonlinear regression settings. Moreover, the bias is not attenuated as the sample size increases. This point is further illustrated in the survey data analyses in which IV‐based estimates of the relevant causal effects diverge substantially from those obtained with appropriate nonlinear estimation methods.

Conclusions.We offer this research as a cautionary note to those who would opt for the use of linear specifications in inherently nonlinear settings involving endogeneity.
Interleukin‐10 reduces scarring and enhances regeneration at a site of sciatic nerve repair
Authors: Atkins Simon , Loescher Alison R. , Boissonade Fiona M. , Smith Keith G. , Occleston Nick , O’Kane Sharon , Ferguson Mark W. J. , Robinson Peter P.
Published: December 2007

Abstract  Axonal regeneration at a site of peripheral nerve repair can be impeded by the formation of scar tissue, which creates a mechanical barrier and initiates the development of multiple branched axonal sprouts that form a neuroma. We have investigated the hypothesis that the application of a scar‐reducing agent to the nerve repair site would permit better axonal regeneration. In anaesthetised C57 Black‐6 mice, the left sciatic nerve was sectioned and immediately re‐approximated using four epineurial sutures. In five groups of eight mice, we injected transforming growth factor‐β3 (50 or 500 ng), interleukin‐10 (IL‐10) (125 or 500 ng), or saline into and around the repair site, both before and after the nerve section. Another group of eight animals acted as sham‐operated controls. After 6 weeks, the outcome was assessed by recording compound action potentials (CAPs), measuring collagen levels using picrosirius red staining, and counting the number of myelinated axons proximal and distal to the repair. CAPs evoked by electrical stimulation distal to the repair were significantly smaller in all repair groups except for the low‐dose IL‐10 group, where they were not significantly different from that in controls. The area of staining for collagen had significantly increased in all repair groups except for the low‐dose IL‐10 group, which was not significantly different from that in controls. The myelinated fibre counts were always higher distal to the repair site, but there were no significant differences between groups. We conclude that administration of a low‐dose of IL‐10 to a site of sciatic nerve repair reduces scar formation and permits better regeneration of the damaged axons.
Modulation of intracellular calcium influences capsaicin‐induced currents of TRPV‐1and voltage‐activated channel currents in nociceptive neurones
Authors: Hagenacker Tim , Büsselberg Dietrich
Published: December 2007

Abstract  Modulation of intracellular calcium ([Ca2+]i) has a major impact on processing of nociceptive signals. While activation of the transient receptor potential vanilloid‐1 (TRPV‐1) receptor/channel complex increases [Ca2+]i by Ca2+ entry from the extracellular space, as well as by Ca2+ release from intracellular stores, the Ca2+ entry through voltage‐activated calcium channels (VACCs) is modulated simultaneously. To clarify the relations between [Ca2+]i and the activation of TRPV‐1 receptor and VACC currents [ITRPV‐1 and ICa(V)], we performed voltage clamp experiments using Ba2+ as well as Ca2+ as a charge carrier. The TRPV‐1 receptor was activated by the application of 0.5 μM capsaicin, and the currents through TRPV‐1 and VACC [ITRPV‐1 and ICa(V)] were measured either when Ca2+ release from intracellular stores was pharmacologically promoted or prevented. With Ba2+ as the divalent charge carrier, capsaicin (0.5 μM) reduced ICa(V) (elicited by a depolarization to 0 mV) to 52.7 ± 4.5% of baseline, and the elicited current through the TRPV‐1 receptor/channel complex was 6.6 ± 0.9% [relative to peak ICa(V)]. These currents were significantly different when Ca2+ was used as charge carrier: the ICa(V) reductions were decreased to 17.8 ± 5.9% of baseline, while the ITRPV‐1 was as high as 57.1 ± 9.1% of ICa(V). Increases of [Ca2+]i by releasing Ca2+ from intracellular stores (using caffeine, 10 mM) before the application of capsaicin increased the ITRPV‐1 (14.1 ± 7%), while the ICa(V) was decreased to 51.6 ± 4.9% compared with control. A preexperimental partial reduction of the Ca2+ release from the stores by dantrolene (5 μM) resulted in less pronounced effects [24.5 ± 8.8%, relative to peak ICa(V)] for ITRPV‐1, and a reduction to 35.4 ± 3% of baseline for ICa(V) after capsaicin application.
Visual prognosis and vitreous cytokine levels after arteriovenous sheathotomy in branch retinal vein occlusion associated with macular oedema
Authors: Shimura Masahiko , Nakazawa Toru , Yasuda Kanako , Kunikata Hiroshi , Shiono Takashi , Nishida Kohji
Published: December 2007

Purpose:  To investigate the relationship between vitreous levels of cytokines, including interleukin‐6 (IL‐6) and vascular endothelial growth factor (VEGF), and visual prognosis after pars plana vitrectomy (PPV) with arteriovenous sheathotomy in patients with branch retinal vein occlusion (BRVO) associated with macular oedema.

Methods:  We studied 60 patients with logMAR visual acuity (VA) scores of < 0.3 and visual impairment secondary to BRVO‐associated macular oedema. All patients underwent PPV with arteriovenous sheathotomy. At the time of PPV, vitreous samples were collected from the operated eye and vitreous levels of VEGF and IL‐6 were measured. Best corrected VA (BCVA) (using a logMAR chart) and foveal thickness (FT) (using optical coherence tomography) were monitored for up to 6 months after PPV.

Results:  Both BCVA and FT significantly improved after PPV. According to multiple regression analysis, both the improvement in BCVA and decrease in FT were closely related to the vitreous level of IL‐6 but not to that of VEGF. The vitreous level of VEGF was strongly correlated with duration of BRVO.

Conclusions:  Both improvement in BCVA and decrease in FT were observed after PPV in BRVO patients with macular oedema. Interestingly, these visual prognoses strongly correlate with the vitreous level of IL‐6, whereas the duration of BRVO strongly correlates with the vitreous level of VEGF.
Trilobate arrowheads at ed‐Dur (U.A.E, Emirate of Umm al‐Qaiwain)
Authors: Delrue Parsival
Published: December 2007

This article discusses the trilobate arrowheads excavated at ed‐Dur during the different campaigns. Special emphasis is placed on the trilobate or three‐lobed type of arrowhead because these appear rather suddenly and are not widespread in southeastern Arabia. The broader cultural, geographical and historical framework of these arrowheads is sketched in order to place the ed‐Dur material in context.
Jabal Haroun during the Islamic period: a study in the light of newly discovered inscriptions (1)
Authors: Al‐Salameen Zeyad , Al‐Falahat Hani
Published: December 2007

This paper tries to shed more light on the history of Islamic Petra and concentrates particularly on the Jabal Haroun area. Five new Islamic inscriptions dated to the early, middle and late Islamic periods are published below for the first time. These confirm the sanctity of the site during these periods.
Titus Andronicus: A Violent Change of Fortunes
Authors: Kingsley‐Smith Jane
Published: December 2007

Titus Andronicus has often been judged to be less than the sum of its parts – perhaps because those parts are so sensational. Yet, in the late twentieth and early twenty‐first centuries, the play has experienced a striking reversal in its critical and theatrical fortunes. This reversal has been based on a perception of the play's integrity, discovered not just in the links between stage properties and language, nor between its violent set‐pieces and its overall structure, but in the play's claim to moral and aesthetic unity. This essay focuses on the critical fortunes of Titus Andronicus in the last fifty years, with particular reference to Julie Taymor's film, Titus (USA, 1999). It engages with issues of violence, language and the body, gender and racial difference, and genre.
Human retinol dehydrogenase 13 (RDH13) is a mitochondrial short‐chain dehydrogenase/reductase with a retinaldehyde reductase activity
Authors: Belyaeva Olga V. , Korkina Olga V. , Stetsenko Anton V. , Kedishvili Natalia Y.
Published: December 2007

Retinol dehydrogenase 13 (RDH13) is a recently identified short‐chain dehydrogenase/reductase related to microsomal retinoid oxidoreductase RDH11. In this study, we examined the distribution of RDH13 in human tissues, determined its subcellular localization and characterized the substrate and cofactor specificity of purified RDH13 in order to better understand its properties. The results of this study demonstrate that RDH13 exhibits a wide tissue distribution and, by contrast with other members of the RDH11‐like group of short‐chain dehydrogenases/reductases, is a mitochondrial rather than a microsomal protein. Protease protection assays suggest that RDH13 is localized on the outer side of the inner mitochondrial membrane. Kinetic analysis of the purified protein shows that RDH13 is catalytically active and recognizes retinoids as substrates. Similar to the microsomal RDHs, RDH11, RDH12 and RDH14, RDH13 exhibits a much lower Km value for NADPH than for NADH and has a greater catalytic efficiency in the reductive than in the oxidative direction. The localization of RDH13 at the entrance to the mitochondrial matrix suggests that it may function to protect mitochondria against oxidative stress associated with the highly reactive retinaldehyde produced from dietary β‐carotene.
Florida nurse practitioners’ attitudes and practices regarding oral cancer prevention and early detection
Authors: Meng Xiaoxian , Duncan R. Paul , Porter Colleen K. , Li Qing , Tomar Scott L.
Published: December 2007

Purpose: To examine Florida nurse practitioners’ (NPs’) attitudes and practices regarding oral cancer prevention and early detection.

Data source: A statewide mail survey was conducted among Florida NPs who provided primary care. The questionnaire was adapted from an existing survey instrument used to measure NPs’ knowledge, attitudes, and practices about oral cancer prevention and early detection. A total of 448 Florida NPs (33% response rate) completed the survey.

Conclusions: Florida NPs reportedly were not well prepared for oral cancer prevention and early detection. Although most NPs realized the importance of annual oral cancer screening for high‐risk populations and held positive attitudes toward the benefit of early detection, only 39.3% of respondents thought his or her knowledge about oral cancer was current and more than half had never provided oral cancer examinations.

Implications for practice: Florida has among the nation’s highest oral cancer rates, but persons at highest risk are among those least likely to see a dentist. Therefore, a multidisciplinary approach involving all relevant healthcare providers, including NPs, may be more effective than relying only on dentists’ efforts in improving survival rates for oral cancer. Strategies are needed to increase the involvement of Florida’s NPs in oral cancer detection.
Making the Perfect Queen: The Cultural Production of Identities in Beauty Pageants
Authors: King‐O’Riain Rebecca Chiyoko
Published: December 2007

Beauty queens are symbolic representations of collective cultural indentities and beauty pageants are fields of active ‘cultural production’. This article surveys the growing literature on beauty pageants to better understand how culture is produced within the contexts of pageants. To do so, the article examines how beauty pageants operate as sites of commodification and consumption in a world increasingly influenced by global markets and media institutions. It also illustrates how culture is produced in beauty pageants by examining beauty pageants as sites of oppression, sites to articulate cultural agency, and sites of ethnic, gender, cultural, and sexual identity production.
Covert Racism in the USA and Globally
Authors: Coates Rodney D.
Published: December 2007

Covert racism, born out of imperialist needs to maximize profit at the expense of racialized others, stands shielded by institutions, culture, stereotypical assumptions, and tradition. Whereas overt racism assumed blatant and insidious forms, covert racism hides behind the façade of ‘politeness’, political correctness and expediency. Racially coded words and calls for racial blindness obfuscate the reality of this subtle, subversive, and often hidden form of racism. Covert racism, just like its twin overt racism, is neither innocent nor harmless. The scars of covert racism, often seen in terms of increased levels of disease, negative sanctions, inadequate information, and lost opportunities – serve to continually victimize racial nonelites.
Democracy, Nationalism and Culture: A Social Critique of Liberal Monoculturalism
Authors: Conversi Daniele
Published: December 2007

Does liberal democracy provide an ideal framework for solving nationalist disputes? Or is rather democracy more conductive to nationalism and conflict? No definitive answer can be given to this broadly formulated question. However, the trend in the scholarly literature has recently pointed towards the latter direction. This article first introduces the ‘demo‐skeptical turn’, which has emerged across disciplines in the study of democratic transitions. It then relates this to an understudied area – cultural homogenization. A social history of cultural homogenization remains yet to be written, but its historical impact is so overwhelming that its key features need to be studies on its own. This is, in turn, related to mainstream concepts of majoritarian liberal democracy.
Work practices and childhood agricultural injury
Authors: Larson-Bright Muree , Gerberich Susan G , Alexander Bruce H , Gurney James G , Masten Ann S , Church Timothy R , Ryan Andrew D , Renier Colleen M
Published: December 2007

Objective:

To evaluate whether children’s agricultural work practices were associated with agricultural injury and to identify injury and work practice predictors.

Design:

Analyses were based on nested case–control data collected by the Regional Rural Injury Study-II (RRIS-II) surveillance study in 1999 and 2001 by computer-assisted telephone interviews.

Subjects:

Cases (n =  425) and controls (n =  1886) were persons younger than 20 years of age from Midwestern agricultural households. Those reporting agricultural injuries became cases; controls (no injury) were selected using incidence density sampling.

Main outcome measures:

Multivariate logistic regression was used to estimate the risks of injury associated with agricultural work, performing chores earlier than developmentally appropriate, hours worked per week, and number of chores performed.

Results:

Increased risks of injury were observed for children who performed chores 2–3 years younger than recommended, compared to being “age-appropriate” (odds ratio (OR)  =  2.6, 95% confidence interval (CI)  =  1.4–4.5); performed any agricultural work (3.9 (2.6–5.6)); performed seven to ten chores per month compared to one chore (2.2 (1.3–3.5)); and worked 11–30 or 31–40 h per week compared to 1–10 h (1.6 (1.2–2.1) and 2.2 (1.3–3.7), respectively). Decreased risks of injury were observed for non-working children compared to children performing what are commonly considered safe levels of agricultural work.

Conclusions:

This study demonstrated elevated risks of agricultural injury among children who perform developmentally inappropriate chores. Results suggest that the efficacy of age restrictions for preventing the occurrence of childhood agricultural injuries warrants further evaluation.
Car safety seats for children: rear facing for best protection
Authors: Henary B , Sherwood C P , Crandall J R , Kent R W , Vaca F E , Arbogast K B , Bull M J
Published: December 2007

This article has been retracted.
Pattern of seat belt wearing in Nanjing, China
Authors: Routley V , Ozanne-Smith J , Li D , Hu X , Wang P , Qin Y
Published: December 2007

Objective:

To describe the patterns of seat belt wearing in Nanjing, China for drivers, front seat passengers, and rear occupants of motor vehicles.

Design:

Roadside observational study.

Setting:

Four sites in central and northern Nanjing during daylight hours over 1 week in April 2005.

Subjects:

Drivers and passengers of 17 147 cars, taxis, goods vans, and pickups, which traveled in the inside traffic lane.

Main outcome measures:

Percentage seat belt wearing for each of seating position, age/sex, time of day, vehicle type, day of week.

Results:

The rate of seat belt wearing was significantly higher in drivers (67.3%, 95% CI 66.6 to 68.0) than front seat passengers (18.9%, 95% CI, 18.0 to 19.8). It was negligible for second front seat passengers (2.6%, 95% CI 0.3 to 4.9) and rear seat passengers (0.5%, 95% CI 0.3 to 0.7). Belt tampering, such that protection would be reduced in the event of a crash, was observed for 18.5% of taxi drivers. Drivers were most likely to wear seat belts in cars and vans and at a city roundabout; front seat passengers were most likely to wear seat belts in non-taxi vehicles, during the evening rush hour, if the driver was wearing a belt, and on the local north road. Drivers were least likely to wear a belt in the early morning, in pickups and taxis, on Tuesday (or the following week), and on the local north road; front seat passengers were least likely to wear a belt in taxis and if the driver was not wearing a belt.

Conclusions:

Rates of seat belt wearing by passengers were low despite national legislation and provincial regulations coming into effect several months before the survey. Combined education and enforcement are necessary accompaniments to legislation.
Association between road vehicle collisions and recent medical contact in older drivers: a case-crossover study
Authors: Leproust Sandy , Lagarde Emmanuel , Suissa Samy , Salmi L Rachid
Published: December 2007

Objective:

To estimate the association between past medical contacts and the risk of vehicle collision in a population of older drivers from the province of Quebec, Canada.

Design:

Case-crossover study.

Setting:

Quebec.

Participants:

111 699 older drivers involved in at least one vehicle collision between January 1988 and December 2000.

Main outcome measures:

For each driver, the risk of having a vehicle collision while exposed and not exposed to a medical contact was compared. Separate conditional logistic regression analyses were conducted for all drivers and in four diagnostic-specific subgroups.

Results:

The study found a weak but statistically significant increased risk of all collisions being associated with a medical contact within 1 month before the collision, for all drivers (OR = 1.10, 95% CI 1.08 to 1.11) and for drivers with diabetes (OR = 1.07, 95% CI 1.03 to 1.11).

Conclusion:

Older drivers who have a collision are more likely to have been in contact with a physician shortly before the collision. These findings suggest that there might be an opportunity to detect medical conditions that put older drivers at higher risk of collision; however, further research is needed to assess the potential effectiveness and practical modalities of screening.
EXPERIMENTAL STUDY OF THE STRUCTURE OF A SOCIAL NETWORK AND HUMAN DYNAMICS IN A VIRTUAL SOCIETY
Authors: GRABOWSKI ANDRZEJ , KRUSZEWSKA NATALIA
Published: December 2007

We study a large social network consisting of 3 × 104 individuals, who interact in a large virtual world of Massive Multiplayer Online Role Playing Games (MMORPGs). On the basis of the players' list of friends and the playing time received from the on-line game server, we investigate the structure of the network and human dynamics. We try to show that the structure of this friendship network is very similar to the structure of different social networks. In order to investigate the relation between networks of acquaintances in virtual and real worlds, we carried out a survey among the players. We found very interesting scaling laws concerning human dynamics. Our research has shown how long people are interested in a single task, and how much time they devote to it. It is surprising that exponent values in both cases are close to minus one.
SELF-ORGANIZATION APPLIED TO DYNAMIC NETWORK LAYOUT
Authors: GEIPEL MARKUS M.
Published: December 2007

As networks and their structure have become a major field of research, a strong demand for network visualization has emerged. We address this challenge by formalizing the well established spring layout in terms of dynamic equations. We thus open up the design space for new algorithms. Drawing from the knowledge of systems design, we derive a layout algorithm that remedies several drawbacks of the original spring layout. This new algorithm relies on the balancing of two antagonistic forces. We thus call it arf for "attractive and repulsive forces". It is, as we claim, particularly suited for a dynamic layout of smaller networks (n < 103). We back this claim with several application examples from ongoing complex systems research.
EMERGENCE OF MULTISCALING IN HETEROGENEOUS COMPLEX NETWORKS
Authors: SANTIAGO A. , BENITO R. M.
Published: December 2007

In this paper we provide numerical evidence of the richer behavior of the connectivity degrees in heterogeneous preferential attachment networks in comparison to their homogeneous counterparts. We analyze the degree distribution in the threshold model, a preferential attachment model where the affinity between node states biases the attachment probabilities of links. We show that the degree densities exhibit a power-law multiscaling which points to a signature of heterogeneity in preferential attachment networks. This translates into a power-law scaling in the degree distribution, whose exponent depends on the specific form of heterogeneity in the attachment mechanism.
EFFECTS OF COMPLEX SYSTEM STRUCTURE AND EXTERNAL FIELD IN OPINION FORMATION
Authors: GUO LONG , CAI XU
Published: December 2007

Around us, the society structure and external field, such as government policy, the newspaper, the internet and other mass media, play a special role in shaping the attitudes, beliefs and public opinion. For studying the role of the society structure and the external field, we propose a new opinion model based on the former models. With computer simulations of opinion dynamics, we find that the smaller the clustering coefficient and the society size, the easier the consensus phase is reached and other interesting results.
MULTI-TEAM PREY-PREDATOR MODEL
Authors: ELETTREBY M. F. , El-METWALLY H.
Published: December 2007

Here, we apply multi team concept to the prey-predator model. The prey teams help each other. Local stability of the system is studied. Global stability and persistence of the model without help are investigated.
PATTERN-BASED EXPLORATION OF DESIGN ALTERNATIVES FOR THE EVOLUTION OF SOFTWARE ARCHITECTURES
Authors: CÔTÉ ISABELLE , HEISEL MARITTA , WENTZLAFF INA
Published: December 2007

We propose a pattern-based software development method comprising analysis (using problem frames) and design (using architectural and design patterns), from which especially evolving systems benefit. Evolution operators guide a pattern-based transformation procedure, including re-engineering tasks for adjusting a given software architecture to meet new system demands. Through application of these operators, relations between analysis and design documents are explored systematically for accomplishing desired software modifications. This allows for reusing development documents to a large extent, even when the application environment and the requirements change.
EAGLE: EFFECTIVE TOOL SUPPORT FOR SHARING ARCHITECTURAL KNOWLEDGE
Authors: FARENHORST RIK , LAGO PATRICIA , VAN VLIET HANS
Published: December 2007

Knowledge management plays an important role in the software architecting process. Recently, this role has become more apparent by a paradigm shift that views a software architecture as the set of architectural design decisions it embodies. This shift has sparked the discussion in both research and practice on how to best facilitate sharing of so-called architectural knowledge, and how tools can best be employed. In order to design successful tool support for architectural knowledge sharing it is important to take into account what software architecting really entails. In this paper, we define the main characteristics of architecting, based on observations in a large software development organization, and state-of-the-art literature in software architecture. Based on the defined characteristics, we determine how best practices known from knowledge management could be used to improve architectural knowledge sharing. This results in the definition of a set of desired properties of architectural knowledge sharing tools. Finally, we highlight the design and implementation of EAGLE, an architectural knowledge sharing portal that implements those properties.
APPLYING MDE TO THE DEVELOPMENT OF FLEXIBLE AND REUSABLE WIRELESS SENSOR NETWORKS
Authors: VICENTE-CHICOTE CRISTINA , LOSILLA FERNANDO , ÁLVAREZ BÁRBARA , IBORRA ANDRÉS , SANCHEZ PEDRO
Published: December 2007

Wireless Sensor Networks (WSN) are a very promising research field since they are applicable in many different areas. Current proposals for WSN system development are mainly focused on implementation issues and rarely use a Software Engineering methodology to support their development life cycle. The Model-Driven Engineering (MDE) approach can be used as a solution to this by allowing designers to model their systems at different abstraction levels, providing them with automatic model transformations to incrementally refine abstract models into more concrete ones. In this vein, this paper presents an MDE approach to WSN application development. Three levels of abstraction have been defined which allow designers to build: (1) domain-specific models, (2) component-based architecture descriptions, and (3) platform-specific models. Automatic model transformations between these three abstraction levels have been designed and, in order to demonstrate the viability of the proposal, a real WSN application has been developed using the implemented tools.
Cks1 Regulates cdk1 Expression: A Novel Role during Mitotic Entry in Breast Cancer Cells
Authors: Westbrook Louise , Manuvakhova Marina , Kern Francis G. , Estes Norman R. , Ramanathan Harish N. , Thottassery Jaideep V.
Published: December 2007

Cks1, a small protein whose expression is strongly associated with aggressive breast tumors, is a component of cyclin-cdk complexes, as well as the SCFSkp2 ubiquitin ligase. In these studies, we explored its roles in estrogen receptor–positive breast tumor cells. When exposed to the antiestrogen ICI 182780, these cells accumulate in G1 by reducing the expression of Cks1, and increasing the levels of p130/Rb2, a cdk2 inhibitor and SCFSkp2 target. Heregulin β1 or estradiol abrogate antiestrogen effects by increasing Cks1 expression, down-regulating p130/Rb2 and inducing S phase entry. Depletion of Cks1 in these cells by RNA interference concomitantly decreased Skp2 and up-regulated p130/Rb2 and another SCFSkp2 target, p27Kip1. Remarkably, however, Cks1-depleted cells not only exhibit slowed G1 progression, but also accumulate in G2-M due to blocked mitotic entry. Notably, we show that cdk1 expression, which is crucial for M phase entry, is drastically diminished by Cks1 depletion, and that restoration of cdk1 reduces G2-M accumulation in Cks1-depleted cells. cdk1 reduction in Cks1-depleted cells is a consequence of a marked decrease in its mRNA and not due to alteration in its proteolytic turnover. Both heregulin β1 and estradiol could neither restore cdk1 nor sustain cycling in Cks1-depleted cells, although classical estrogen receptor function remained unaltered. Cks1 depletion also decreased Skp2 in human mammary epithelial cells without altering cell cycle progression. Thus, the indispensability of Cks1 to the breast cancer cell cycle, versus its redundancy in normal cells, suggests that Cks1 abrogation could be an effective interventional strategy in breast cancer. [Cancer Res 2007;67(23):11393–401]
WP1066 Disrupts Janus Kinase-2 and Induces Caspase-Dependent Apoptosis in Acute Myelogenous Leukemia Cells
Authors: Ferrajoli Alessandra , Faderl Stefan , Van Quin , Koch Patricia , Harris David , Liu Zhiming , Hazan-Halevy Inbal , Wang Yongtao , Kantarjian Hagop M. , Priebe Waldemar , Estrov Zeev
Published: December 2007

Several cytokines and growth factors that stimulate the proliferation of acute myelogenous leukemia (AML) cells transduce their signals by activating the transcription factor Janus-activated kinase 2 (JAK2). Accordingly, the inhibition of JAK2 or of its downstream signaling pathways suppresses the proliferation of AML cells. Because (E)-3(6-bromopyridin-2-yl)-2-cyano-N-((S0-1-phenylethyl)acrylamide) (WP1066) is a novel analogue of the JAK2 inhibitor AG490, we tested its activity in AML cells and investigated its mechanism of action. Using clonogenic assays, we found that although WP1066 had a marginal effect on normal marrow progenitors, it inhibited the proliferation of AML colony-forming cells obtained from patients with newly diagnosed AML and that of the AML cell lines OCIM2 and K562. WP1066 inhibited OCIM2 cell multiplication by inducing accumulation of cells at the G0-G1 phase of the cell cycle. Similar to its parent compound AG490, WP1066 inhibited the phosphorylation of JAK2, but unlike AG490, WP1066 also degraded JAK2 protein, thereby blocking its downstream signal transducer and activator of transcription (STAT) and phosphoinositide-3-kinase pathways. These effects resulted in the activation of the caspase pathway. Incubation of both OCIM2 and K562 cells with WP1066 activated caspase-3, induced cleavage of poly(ADP-ribose) polymerase, and caused caspase-dependent apoptotic cell death. Thus, WP1066 is a potent JAK2 inhibitor whose effects in AML and other hematologic malignancies merit further investigation. [Cancer Res 2007;67(23):11291–9]
Neuroblastoma Cells Isolated from Bone Marrow Metastases Contain a Naturally Enriched Tumor-Initiating Cell
Authors: Hansford Loen M. , McKee Amy E. , Zhang Libo , George Rani E. , Gerstle J. Ted , Thorner Paul S. , Smith Kristen M. , Look A. Thomas , Yeger Herman , Miller Freda D. , Irwin Meredith S. , Thiele Carol J. , Kaplan David R.
Published: December 2007

Neuroblastoma is a heterogeneous pediatric tumor thought to arise from the embryonic neural crest. Identification of the cell responsible for propagating neuroblastomas is essential to understanding this often recurrent, rapidly progressing disease. We have isolated and characterized putative tumor-initiating cells from 16 tumors and bone marrow metastases from patients in all neuroblastoma risk groups. Dissociated cells from tumors or bone marrow grew as spheres in conditions used to culture neural crest stem cells, were capable of self-renewal, and exhibited chromosomal aberrations typical of neuroblastoma. Primary spheres from all tumor risk groups differentiated under neurogenic conditions to form neurons. Tumor spheres from low-risk tumors frequently formed large neuronal networks, whereas those from high-risk tumors rarely did. As few as 10 passaged tumor sphere cells from aggressive neuroblastoma injected orthotopically into severe combined immunodeficient/Beige mice formed large neuroblastoma tumors that metastasized to liver, spleen, contralateral adrenal and kidney, and lung. Furthermore, highly tumorigenic tumor spheres were isolated from the bone marrow of patients in clinical remission, suggesting that this population of cells may predict clinical behavior and serve as a biomarker for minimal residual disease in high-risk patients. Our data indicate that high-risk neuroblastoma contains a cell with cancer stem cell properties that is enriched in tumor-initiating capacity. These cells may serve as a model system to identify the molecular determinants of neuroblastoma and to develop new therapeutic strategies for this tumor. [Cancer Res 2007;67(23):11234–43]
Traf1 Induction and Protection from Tumor Necrosis Factor by Nuclear Factor-κB p65 Is Independent of Serine 536 Phosphorylation
Authors: Sasaki Carl Y. , Slemenda Colin F. , Ghosh Paritosh , Barberi Theresa J. , Longo Dan L.
Published: December 2007

Abnormal nuclear factor-κB (NF-κB) signaling has been attributed to the initiation and progression of cancer. Posttranslational modification of p65 facilitates optimal NF-κB signaling after activation. Here, we show that the phosphorylation of serine 536 was required for p65-mediated transcription and IκBα expression in fibroblasts. Furthermore, tumor necrosis factor (TNF) treatment slightly induced p65 phosphorylation, and both unphosphorylated and phosphorylated p65 translocated into the nucleus. The phosphorylation of serine 536 was not required for p65-mediated protection from TNF cytotoxicity and Traf1 induction in fibroblasts. Also, the corecruitment of p65 and RNA polymerase II to the Traf1 enhancer region did not require p65 phosphorylation. However, the corecruitment of p65 and RNA polymerase II to the Csf2 promoter required the phosphorylation of serine 536. These findings suggested that the requirement of serine phosphorylation at residue 536 and the distance between the NF-κB response element and the start of transcription may influence which genes will be transcribed. [Cancer Res 2007;67(23):11218–25]
Delta-like 4 Notch Ligand Regulates Tumor Angiogenesis, Improves Tumor Vascular Function, and Promotes Tumor Growth In vivo
Authors: Li Ji-Liang , Sainson Richard C.A. , Shi Wen , Leek Russell , Harrington Laura S. , Preusser Matthias , Biswas Swethajit , Turley Helen , Heikamp Emily , Hainfellner Johannes A. , Harris Adrian L.
Published: December 2007

The vascular endothelial growth factor (VEGF) plays a key role in tumor angiogenesis. However, clinical trials targeting the VEGF pathway are often ineffective, suggesting that other factors/pathways are also important in tumor angiogenesis. We have previously shown that the Notch ligand Delta-like 4 (DLL4) is up-regulated in tumor vasculature. Here, we show that DLL4, when expressed in tumor cells, functions as a negative regulator of tumor angiogenesis by reducing the number of blood vessels in all five types of xenografts, but acts as a positive driver for tumor growth in two of them (human glioblastoma and prostate cancer). The growth of in vivo models was not related to the effects on growth in vitro. DLL4 expressed in the tumor cells activated Notch signaling in host stromal/endothelial cells, increased blood vessel size, and improved vascular function within tumors. The promotion of tumor growth was, to some extent, due to a reduction of tumor hypoxia and apoptosis. DLL4-expressing tumor cells responded to anti-VEGF therapy with bevacizumab. A soluble form of DLL4 (D4ECD-Fc) blocked tumor growth in both bevacizumab-sensitive and bevacizumab-resistant tumors by disrupting vascular function despite increased tumor vessel density. In addition, we show that DLL4 is up-regulated in tumor cells and tumor endothelial cells of human glioblastoma. Our findings provide a rational basis for the development of novel antiangiogenic strategies via blockade of DLL4/Notch signaling and suggest that combined approaches for interrupting both DLL4 and VEGF pathways may improve antiangiogenic therapy. [Cancer Res 2007;67(23):11244–53]
Drug Sensitivity Prediction by CpG Island Methylation Profile in the NCI-60 Cancer Cell Line Panel
Authors: Shen Lanlan , Kondo Yutaka , Ahmed Saira , Boumber Yanis , Konishi Kazuo , Guo Yi , Chen Xinli , Vilaythong Jill N. , Issa Jean-Pierre J.
Published: December 2007

Aberrant promoter hypermethylation and associated gene silencing are epigenetic hallmarks of tumorigenesis. It has been suggested that aberrant DNA methylation can affect the sensitivity of cancers to antineoplastic agents by altering expression of genes critical to drug response. To study this issue, we used bisulfite PCR to assess DNA methylation of 32 promoter-associated CpG islands in human cancer cell lines from the National Cancer Institute (NCI) drug-screening panel (NCI-60 panel). The frequency of aberrant hypermethylation of these islands ranged from 2% to 81% in NCI-60 cancer cells, and provided a database that can be analyzed for the sensitivity to ≈30,000 drugs tested in this panel. By correlating drug activity with DNA methylation, we identified a list of methylation markers that predict sensitivity to chemotherapeutic drugs. Among them, hypermethylation of the p53 homologue p73 and associated gene silencing was strongly correlated with sensitivity to alkylating agents. We used small interfering RNA to down-regulate p73 expression in multiple cell lines, including the resistant cell lines TK10 (renal cancer) and SKMEL28 (melanoma). Down-regulating p73 substantially increased sensitivity to commonly used alkylating agents, including cisplatin, indicating that epigenetic silencing of p73 directly modulates drug sensitivity. Our results confirm that epigenetic profiles are useful in identifying molecular mediators for cancer drug sensitivity (pharmaco-epigenomics). [Cancer Res 2007;67(23):11335–43]
Novel Quinazoline-Based Compounds Impair Prostate Tumorigenesis by Targeting Tumor Vascularity
Authors: Garrison Jason B. , Shaw Yeng-Jeng , Chen Ching-Shih , Kyprianou Natasha
Published: December 2007

Previous evidence showed the ability of the quinazoline-based α1-adrenoreceptor antagonist doxazosin to suppress prostate tumor growth via apoptosis. In this study, we carried out structural optimization of the chemical nucleus of doxazosin and a subsequent structure-function analysis toward the development of a novel class of apoptosis-inducing and angiogenesis-targeting agents. Our lead compound, DZ-50, was effective at reducing endothelial cell viability via a nonapoptotic mechanism. Treatment with DZ-50 effectively prevented in vitro tube formation and in vivo chorioallantoic membrane vessel development. Confocal microscopy revealed a significantly reduced ability of tumor cells to attach to extracellular matrix and migrate through endothelial cells in the presence of DZ-50. In vivo tumorigenicty studies using two androgen-independent human prostate cancer xenografts, PC-3 and DU-145, showed that DZ-50 treatment leads to significant suppression of tumorigenic growth. Exposure to the drug at the time of tumor cell inoculation led to prevention of prostate cancer initiation. Furthermore, DZ-50 resulted in a reduced formation of prostate-tumor derived metastatic lesions to the lungs in an in vivo spontaneous metastasis assay. Thus, our drug discovery approach led to the development of a class of lead (quinazoline-based) compounds with higher potency than doxazosin in suppressing prostate growth by targeting tissue vascularity. This new class of quinazoline-based compounds provides considerable promise as antitumor drugs for the treatment of advanced prostate cancer. [Cancer Res 2007;67(23):11344–52]
Novel NBS1 Heterozygous Germ Line Mutation Causing MRE11-Binding Domain Loss Predisposes to Common Types of Cancer
Authors: Ebi Hiromichi , Matsuo Keitaro , Sugito Nobuyoshi , Suzuki Motoshi , Osada Hirotaka , Tajima Kazuo , Ueda Ryuzo , Takahashi Takashi
Published: December 2007

DNA damage response (DDR) pathways maintain genomic stability. A 657del5 mutation of NBS1, a key DDR component, causing the rare cancer-predisposing Nijmegen breakage syndrome has been reported nearly exclusively in Slavic populations. In this study, we describe the first identification in a Japanese population of an unprecedented type of heterozygous NBS1 mutant, termed IVS11+2insT, lacking the MRE11- and ATM-binding site at the COOH terminus. Profoundly defective in crucial binding to MRE11, MDC1, BRCA1, and wild-type NBS1, the mutant caused impaired ATM phosphorylation in response to low-dose irradiation in a heterozygous state. Importantly, whereas IVS11+2insT was found in only 2 (0.09%) of 2,348 control subjects, it was identified in 2% (2 of 96) of heterozygotes with gastric cancer, 0.8% (3 of 376) of those with colorectal cancer, and 0.4% (2 of 532) of those with lung cancer, which were comparable to frequencies reported for other DDR-related genes known to confer cancer susceptibility. The presence of the heterozygous IVS11+2insT mutation seemed to be associated with an increased risk for gastrointestinal cancers, with an odds ratio of 12.6 and 95% confidence interval (95% CI) of 2.05 to 132.1 (P = 0.0001). The odds ratios separately calculated for gastric and colorectal cancers were 25.0 (95% CI, 1.78–346.0) and 9.43 (95% CI, 1.08–113.1), respectively. These findings suggest that IVS11+2insT is associated with an increased risk for the development of certain types of common cancers, warranting future investigation including detailed phenotypic characterization of age of onset and penetrance in heterozygotes, as well as screening in other ethnic groups. [Cancer Res 2007;67(23):11158–65]
Sigma-1 Receptors Bind Cholesterol and Remodel Lipid Rafts in Breast Cancer Cell Lines
Authors: Palmer Christopher P. , Mahen Robert , Schnell Eva , Djamgoz Mustafa B.A. , Aydar Ebru
Published: December 2007

Lipid rafts are membrane platforms that spatially organize molecules for specific signaling pathways that regulate various cellular functions. Cholesterol is critical for liquid-ordered raft formation by serving as a spacer between the hydrocarbon chains of sphingolipids, and alterations in the cholesterol contents of the plasma membrane causes disruption of rafts. The role that σ receptors play in cancer is not clear, although it is frequently up-regulated in human cancer cells and tissues and σ receptors inhibit proliferation in carcinoma and melanoma cell lines, induce apoptosis in colon and mammary carcinoma cell lines, and reduce cellular adhesion in mammary carcinoma cell lines. In this study, we provide molecular and functional evidence for the involvement of the enigmatic σ1 receptors in lipid raft modeling by σ1 receptor–mediated cholesterol alteration of lipid rafts in breast cancer cell lines. Cholesterol binds to cholesterol recognition domains in the COOH terminus of the σ1 receptor. This binding is blocked by σ receptor drugs because the cholesterol-binding domains form part of the σ receptor drug-binding site, mutations of which abolish cholesterol binding. Furthermore, we outline a hypothetical functional model to explain the myriad of biological processes, including cancer, in which these mysterious receptors are involved. The findings of this study provide a biological basis for the potential therapeutic applications of lipid raft cholesterol regulation in cancer therapy using σ receptor drugs. [Cancer Res 2007;67(23):11166–75]