bluuebunny/crossref_metadata_2025 huggingface dataset:
Employee Participation in a Hospital Hazard Management System
Authors: Cohen H. Harvey , Cohen Joseph
Published: April 2011

A case study in a health care facility identifies and reduces injuries using participatory ergonomics.
Moving Horizons, Control Reversals, and Graveyard Spirals
Authors: Roscoe Stanley N.
Published: April 2011

Might an attitude display with a flight path predictor help to prevent accidents such as the JFK Jr. crash in 1999?
Tips for Creating a Safety Culture in Organizations
Authors: Wilson-Donnelly Katherine A. , Priest Heather A. , Burke C. Shawn , Salas Eduardo
Published: April 2011

Establishing, supporting, communicating, and implementing clear safety policies will always benefit any organization.
When to Ignore What Users Say
Authors: Klein Devorah E.
Published: April 2011

Observations of people's actual behavior often contradict their self-perceptions and can lead to better solutions and improvements.
A Human-Centered Approach to Designing Improved Fall-Arrest Equipment
Authors: Kohlis B. , Shekar A.
Published: April 2011

A systematic human factors approach to designing fall protection equipment ensures improved performance, ease of use, comfort, and market acceptance.
The ExperiCycle: A Platform for Bicycle Design Research
Authors: Stevens Edward M.
Published: April 2011

Students delve into research on bicycle MSDs and create a tool to improve studies of future designs.
Reviews of Human Factors and Ergonomics, Volume I
Authors: Nickerson Raymond S.
Published: April 2011

2006, 264 pages, $80.00 for HFES members Santa Monica, CA: Human Factors and Ergonomics Society ISBN 0-945289-25-1 Reviewed By William C. Howell
Laws & Rules: Subscribed Content Boomer, Sooner, and Donders
Authors: Peacock Brian , Fogelman Max
Published: April 2011

Boomer, Sooner, and Donders
Human Factors Goes to the Golf Course: Knowledge Engineering of Commercial Mowing
Authors: Sanchez Julian , Bowles C. Travis , Rogers Wendy A. , Fisk Arthur D.
Published: April 2011

Before a new fairway mower can be made more user-centered, steps must be taken to understand how operators interact with the existing model.
A Look Back: IBM-Owego Human Factors in the 1970s
Authors: Shafer John B.
Published: April 2011

This article is part of a special series in honor of the upcoming HFES 50th Anniversary. The first article was published in the summer 2006 issue, and “A Look Back” continues through fall 2007.
Addressing Hand Pain in Podiatry
Authors: Halford Victoria , Cohen H. Harvey , Birch Ivan
Published: April 2011

A qualitative study reveals a range of possible ergonomic risk factors that may lead to hand pain among an understudied group of health care practitioners.
Developing Icons and Symbols: A Comparison of Two Methods
Authors: MacBeth Scott A. , Moroney William F. , Biers David W.
Published: April 2011

Meaningful symbols and icons are more likely to result from the active exchange of ideas fostered by the focus group method.
Designing for Older People
Authors: Kroemer Karl H. E.
Published: April 2011

Knowledge of age-related impairments in vision, hearing, and cognition can aid designers of products, tools, and environments for older users.
A Look Back: The Early Days of Software Usability
Authors: Schaffer Eric
Published: April 2011

This article is part of a special series in honor of the upcoming HFES 50th Anniversary. The first article was published in the summer 2006 issue, and “A Look Back” continues through fall 2007.
Potential Capabilities in a Future, Augmented Cockpit
Authors: Comerford Doreen , Johnson Walter W.
Published: April 2011

Future displays that combine images from the real and virtual worlds offer the promise of enhanced information and performance for operators.
Mental Preparation for Flying
Authors: Murray Steve
Published: April 2011

FEATURE AT A GLANCE: In this article, I contend that an often-overlooked aspect of preflight preparation is mental preparedness. Specifically, I discuss chronic stress and the negative effects of such stress on human performance abilities in complex situations. I conclude with a recommendation that aircrew training and procedures should incorporate some of the stress management techniques developed by clinical and counseling psychologists. At the very least, pilots should be encouraged to set aside quiet contemplation time prior to every flight to consider their mental preparedness.
Lifespan Perspectives on the Foreseeable Use of Consumer Products
Authors: Beran Melissa , Nielsen Elizabeth , Altkorn Robert , Milkovich Scott , Rider Gene
Published: April 2011

FEATURE AT A GLANCE: The determination of foreseeable use – both the unintended and intended uses of consumer products – should be central in the development of any safe product. One of the factors influencing foreseeable use is the age of the potential user. Different age groups have different drivers, which can potentially affect product development. The purpose of this article is to call attention to these drivers and to demonstrate their importance in determining foreseeable use and, in turn, their importance for product safety.
Research of a Different Kind
Authors: Hornick Richard J.
Published: April 2011

The arena of forensics often requires that the human factors expert witness do research that deviates from the classical paradigm of rigid control of independent variables to obtain resulting data. Indeed, in the judicial process, an experiment with only one independent variable and a single subject (or device) may reach beyond statistical significance and be vitally pivotal to judicial decisions. This article provides examples in which very limited research experiments were conducted by the author and that provided critical data to assist juries to reach conclusions pertinent to human behavior and equipment design in accident situations.
The Role of Physical Ergonomics in Litigation
Authors: Fernandez Jeffrey E. , Ware Brandy Farris , Marley Robert J. , Kumar Anil R.
Published: April 2011

The primary goal of the ergonomist is to develop systems and products that increase productivity, function intuitively, and minimize the user’s risk of injury and illness. Injuries occur when a system or product does not fit or was not designed for the capabilities of the user. The physical ergonomist plays an important role in litigation in reducing the risk of large damages or settlements through improved design. This article outlines three cases that demonstrate how a physical ergonomist uses established methods and techniques to analyze litigation cases.
Implementing Bent-Handled Tools in the Workplace
Authors: Dempsey Patrick G. , Leamon Tom B.
Published: April 2011

Don't assume that a tool developed for one task will be applicable to all tasks requiring the same tool.
On the time-dependent, thermal and non-Newtonian elastohydrodynamic lubrication of line contacts subjected to normal and tangential vibrations
Authors: Yang P , Jin Z M , Liu F , Dowson D
Published: April 2011

Complete numerical solutions were obtained for the time-dependent thermal elastohydrodynamic lubrication (EHL) of line contacts under combined vertical and longitudinal vibrations. It was assumed that the contact was composed of two infinitely long steel rollers. These rollers were then simplified as an infinite plane and an equivalent roller. The lubricant was assumed to be a Ree-Eyring non-Newtonian fluid. The time-dependent numerical solutions were achieved instant after instant in each period of vibrations. The periodic error was checked at each end of the vibration period until the responses of pressure, film thickness and temperature were all periodic functions with the frequency of the roller's vibrations. At each instant, the pressure field was solved with a multi-grid method, the surface deformation was solved with a multi-level multi-integration technique, and the temperature field was solved with a finite difference scheme through a sweeping process. It was shown that the normal vibration dominated the EHL characteristics and could be either strengthened or weakened slightly depending on the phase of the tangential vibration. It was also found that the vibration of the roller could produce transient surface dimples within the contact conjunction.
Steady-state and stability characteristics of hydrostatic two-layered porous oil journal bearings
Authors: Saha N , Majumdar B C
Published: April 2011

Steady state and stability characteristics of hydrostatic two-layered porous oil journal bearings are obtained. The governing differential equations are solved numerically using the finite difference method for a wide range of design parameters. The effects of the eccentricity ratio, slenderness ratio, bearing number, feeding parameter and anisotropy of permeability on the load-carrying capacity, attitude angle, friction variable and oil flowrate have been investigated. Stability analysis has been performed using the linearized perturbation method. It has been observed that a two-layered porous bearing gives higher stability than a single-layered porous bearing.
Numerical analysis of experimental observations of a single transverse ridge passing through an elastohydrodynamic lubrication point contact under rolling/sliding conditions
Authors: Félix-Quiñonez A , Ehret P , Summers J L
Published: April 2011

Recent experimental observations by Félix-Quiñonez, Ehret and Summers ( Trans. ASME, J. Tribology, 2003, 125, 252–259) for a single, flat-top transverse ridge passing through an elastohydrodynamic lubrication (EHL) point contact under various slide-roll ratios have revealed some unexpected features. In particular, under sliding conditions the ridge was observed to sustain additional deformations in the high-pressure region of the contact and an entrapped amount of lubricant was seen to accompany the ridge during its passage through the conjunction and, contrary to current knowledge, appeared not to move at the entraining velocity. This paper analyses the experimental observations by means of a direct comparison with numerical simulations. The numerical results show that the main contributing factor towards the experimentally observed accumulation of lubricant is a reduced lubricant viscosity via shear thinning effects. For the operating conditions considered in this study, internal heating of the lubricant is found to be negligible. In addition, it is shown that the amount of lubricant accumulation is dependent on the geometry of the ridge. Compared to a defect with a Gaussian shape, it is further shown that a greater accumulation of lubricant occurs with the flat-top ridge due to the generation of larger pressure gradients.
Constructing Shou-nyus’ identity and desire: The politics of translation in Taiwanese Sex and the City
Authors: Yang Irene Fang-chih
Published: April 2011

In examining the visibility of Shou-nyus through Diaries of Shou-nyus’ Desire, this article argues that the formation of Shou-nyu identity should be geo-culturally situated. In this context, globalization is the objective condition for subject constitution in Taiwan, popularizing and localizing auratic commodities like Sex and the City as the primary resources for highly mediated Shou-nyu identity. In translating Sex and the City to Taiwan, American hegemony and a celebrity system legitimating and promoting consumption function as the two dominant modes of interpretation. Another local mechanism — heteronormative culture, one that relies on the de-politicization and privatization of women’s intimacy and work — also frames and tames the local version of Sex and the City. The exclusion of political themes, however, relies on the construction of an abject other, the ‘ obason’ (the popular description of the middle-aged and unsophisticated ‘auntie’). Fear of becoming an obason is alleviated through consumption to achieve a more cosmopolitan and urbane Shou-nyu identity, which in turn, facilitates the workings of global capitalism.
Post-Confucian East Asian television dramas: Staging medical politics inside the White Tower
Authors: Liew Kai Khiun
Published: April 2011

Between 2003 and 2007, three versions of the Japanese novel, Shiroi Kyotou ( The Great White Tower) were screened as television drama serials in Japan (2003), Taiwan (2006) and South Korea (2007). The phenomenon of White Tower reflects the vibrant multiculturality and transnationality of East Asian television dramas. Accordingly, this article seeks to use the various narratives of White Tower as manifestations of the underlying tensions of post-authoritarian and post-miracle economies of Taiwan, South Korea and Japan. While audiences are awed by the technologically sophisticated hospital settings and the rigidly disciplined health professionals in the productions, they are also exposed to the ugly realities of cronyism, neglect and arrogance of the predominantly male medical elite. Given the conservatism of most mainstream television dramas, the challenge here is to determine how to interpret the latest versions of White Tower as simultaneously exhibitions and critiques of Asian modernity.
Of prince charming and male chauvinist pigs: Singaporean female viewers and the dream-world of Korean television dramas
Authors: Chan Brenda , Wang Xueli
Published: April 2011

In recent years, there has been a phenomenal rise in the popularity of South Korean television dramas, pop music, movies, fashion and celebrities in East and Southeast Asia. Korean television dramas are a significant component of this cultural diffusion known as the ‘Korean Wave’. Through focus group interviews with female viewers in Singapore, this study seeks to explore how Singaporean women make sense of Korean TV dramas (K-dramas) as female subjects living in the gender hierarchy of their society, and how K-dramas become resources for reflexivity for them.
The search for an Asian Idol: The performance of regional identity in reality television
Authors: Tay Jinna
Published: April 2011

This article examines the prolific international adaptation of reality television programmes in Asia through the Asian Idol phenomenon. For the first time in Asia, a regional song contest, Asian Idol, is held in Jakarta, Indonesia organized in the Pop Idol format. As the Idol series is a longstanding television hit across many Asian countries, Asian Idol can be seen as a test of the format’s transferability to another cultural environment. More interestingly, it can be seen as a professed ‘search’ or more accurately, a ‘performance’ of possible regional identities. Telecast over three nights and going live through television production deals across the six participating countries, two questions arise. Does Asian Idol perhaps hope to herald or take advantage of a form of growing pan-regional celebritism? In adopting a new innovative system of interactive voting and building an online forum for the show, what form of Asian identity did it hope to produce or ‘find’ through this production? This article examines these cultural issues and considers the primary role television may still play as the nationalized platform for cultivating such regional exhibitions.
What was Fight Club? Theses on the value worlds of trash capitalism
Authors: Henderson George L.
Published: April 2011

Since its 1999 theatrical release, Fight Club has been a cult favorite notable for the regular punches thrown and received by its protagonists. How should we read these thrashings alongside what is arguably the film’s other great obsession, trash? I argue that Fight Club’s trash is no mere adjunct or prop for the story; it is the central value-theoretic object structuring the film. Drawing upon recent literatures that urge us to value trash, the paper has three objectives: to reevaluate Fight Club’s representation of capitalism, to develop a value-theoretic account of trash, and, by extension, to explore what that account implies for a broad conception of capitalist value and its origins in human ‘species being’ (Marx). I argue that when trash is defined not simply as the unusable remains of commodities but as matter ‘out of place’, and when any assemblage, including human species being can be shown to consist, in its being, of matter ‘out of place’, trash can be glimpsed as the condition of possibility for value. Value, however, appears otherwise, as a chain of ordered emplacements. I read Fight Club as the stage upon which these contradictory value conceptions are played out and as a provocation to consider the politics of misrecognition that result from value appearing as other than what it is.
Constellations of ferry (im)mobility: islandness as the performance and politics of insulation and isolation
Authors: Vannini Phillip
Published: April 2011

Drawing from three years of fieldwork — including over 250 journeys and about 400 interviews — conducted in ferry-dependent coastal and insular communities of British Columbia, this paper extends the concept of constellation of mobility and provides empirical evidence to argue for its relevance. Coined by Cresswell, the concept of constellations of mobility refers to historically and geographically specific formations of movement inclusive of relational experiences, practices, and politics. By focusing on two of the constitutive parts indicated by Cresswell (experience and route) and a third one originally developed here (remove) ethnographic data description and analysis show how ferry (im)mobility in ferry-dependent communities contributes to spatializing dynamics of insulation and isolation. Positive affective aspects of these spatializations, such as uniqueness and distinction, place-attachment, sense of place, place-identity, safety, connection, and remoteness, as well as negative aspects, such as marginalization, divisiveness, disconnection, fear, and confinement are outlined.
Political judgment beyond paralysis and heroism
Authors: Thaler Mathias
Published: April 2011

This paper seeks to contribute to the literature on political judgment by proposing that the faculty of judgment is essential for responsibly coping with the undeniable fact of distant suffering and the controversial duty of humanitarian intervention. To achieve this end, Mahmood Mamdani’s text ‘The Politics of Naming: Genocide, Civil War, Insurgency’ will be mobilized for a constructive dialogue about which specific conception of political judgment is at stake when we debate a situation like Darfur today. The main claim is that political judgment in times of acute crisis requires the members of the public sphere to strike a precarious balance between two contradictory impulses: the deliberative impulse to enlarge the pool of particular standpoints, and the decisionist impulse to finally bring the conversation to a halt and adopt a normative stance. The theoretical framework for this balanced view of the faculty of judgment will be articulated through a hybridization of Hannah Arendt’s notion of an ‘enlarged mentality’ and Jacques Derrida’s concept of an ‘aporetic decision’.
Team Size, Team Role, Communication Modality, and Team Coordination in the Distributed Operation of Multiple Heterogeneous Unmanned Vehicles
Authors: Fincannon Thomas , Keebler Joseph R. , Jentsch Florian , Phillips Elizabeth , Evans A. William
Published: April 2011

The aim of this study was to investigate the effects of team size, communication modality, and team role on measures of team process over time. As the use of semiautonomous, unmanned vehicles increases, it is pertinent to investigate issues associated with the human teams that will control them, including consideration of team roles and the design of systems to support these roles. Using a 1:35 scale facility for military operations in urban terrain, distributed teams of two or three operators used a simulated, unmanned aerial vehicle and a scaled, unmanned ground vehicle to complete two distinct phases of a mission. The teams used either audio or instant messaging for communication, and the analysis of communication assessed their discussion of target identification, target classification, object localization, and vehicle navigation. Findings indicate that the addition of a third teammate resulted in greater role specificity, and the use of audio increased communication of task-relevant content. The proper assignment of team roles can improve the ability of a team to both acquire and synthesize information from remote environments. Furthermore, proper system design can improve the flow of information between teammates over time.
Robotic Displays for Dismounted Warfighters
Authors: Oron-Gilad Tal , Redden Elizabeth S. , Minkov Yaniv
Published: April 2011

This study investigated the scalability of unmanned vehicle displays for dismounted warfighters. Task performance, workload, and preferences for three display devices were examined in two operational settings: teleoperation of an unmanned ground vehicle (UGV) and intelligence gathering from a remote unmanned vehicle. Previous research has demonstrated variability in operational needs with regard to active teleoperation versus passive intelligence gathering. Thus, it was important to identify whether there was actually a dichotomy between the two in terms of screen space requirements and whether this difference stems from task differences or other factors. Thirty-one soldiers participated in a field study at Fort Benning, Georgia. They were required to perform teleoperation and intelligence-gathering tasks. Results reconfirmed the hypothesis that display type influences performance in intelligence-related tasks that require the use of video feed and digital map. No significant differences among display types were found in the UGV teleoperation task. Dismounted warfighters can adequately perform both active and passive duties with a handheld device on which the video window is as small as 4.3 inches in diameter. However, monocular helmet-mounted displays for robotic displays can be problematic and should be carefully assessed before use in dismounted warfighters’ missions.
Development of a practical toolkit using participatory action research to address health inequalities through NGOs in the UK: Challenges and lessons learned
Authors: Chirewa Blessing
Published: April 2011

This study aimed to develop a practical toolkit to support non-government organizations (NGOs) in tackling health inequalities in the UK and to highlight the challenges and lessons learned. A mixed qualitative methodology within an action research framework was conducted. Semi-structured questionnaires, focus group interviews and discussions with an expert reference group aimed to identify the important themes and produce the toolkit content. A practical guide of information materials for NGOs working on addressing health inequalities was subsequently developed and successfully piloted. The experience of using participatory action research revealed a number of lessons and challenges. The key challenges were lack of training and experience in conducting action research, costs and insufficient resources, slow and time-consuming process, lack of commitment from marginalized groups, and differences in emphasis of goals and vision among participants. The main lessons learned were importance of effective leadership and project management skills, importance of integrating researchers and the researched as equal partners, creation and nurturing of trust, importance of evaluating and piloting processes, importance of engaging with marginalized groups, and use of evidence base in decision making. The lessons and challenges enumerating herein are of value to researchers aiming to implement participatory action research in developing checklists, tools, practical guidance and frameworks, and they offer important areas to consider before starting such projects. In addition, this offers an insight into how the dynamics of participatory action research methodology evolved in the development of the toolkit. Future research and initiatives in this area should focus on ways to improve the toolkit and make it more relevant to a wider community, and methods for evaluating the impact of the toolkit on practice.
Effects of antimony addition and section size on formation of chunky graphite in ductile iron
Authors: Diao X G , Ning Z L , Cao F Y , Ren S Z , Sun J F
Published: April 2011

The combined effects of section size together with antimony addition on formation of chunky graphite in ductile iron were investigated by characterising graphite morphology, nodule count and size. Results show that the increased casting section size leads to an increase in spheroidal graphite diameter and a decrease in graphite nodule count. Meanwhile, all the graphite is spheroidal except in 90 mm thickness casting, in which chunky graphite clearly emerges. Moreover, the same tendency concerning graphite nodule count and size is observed in castings with 0·012 mass-% antimony addition as cooling rate decreases. However, the graphite nodule is refined compared with the Sb free castings, and chunky graphite is absent in 90 mm thickness casting effectively. It is believed that high graphite nodule count suppresses chunky graphite formation in thicker casting because of antimony addition, which has no evident effect on graphite morphology when the casting thickness sizes are less than 90 mm.
An experimental and modelling study of brittle cleavage crack propagation in transformable ferritic steel
Authors: Hughes G M , Smith G E , Crocker A G , Flewitt P E J
Published: April 2011

Flaws that can be present within pressure vessels, pipework and other engineering structures are assessed using the principles of engineering fracture mechanics. It is necessary to support such an approach with an understanding of the underlying fracture mechanisms. Moreover, many of these components are fabricated using transformable steels. In the present paper, the authors describe the fracture of an A508 type steel, heat treated to produce a tempered bainitic microstructure, and subsequently impact tested at −196°C. In particular, focused ion beam microscopy has been used to produce high resolution fractography, combined with information relating to the underlying microstructure and crystallography. The results of cleavage crack propagation across prior austenite grain, lath packet and lath boundaries are described and then correlated with predictions from a three-dimensional geometric model of brittle cleavage fracture in polycrystalline steel. This model includes a consideration of a lath substructure developed within the grains and is based upon a Kurdjumov–Sachs orientation relationship with the parent austenite grain.
Microstructure characterisation of solution treated (ST) and solution treated and aged (STA) Incoloy 909
Authors: Balachander M A , Vishwakarma K , Tang B , Richards N L
Published: April 2011

A microstructural analysis has been carried out on the commercially solution treated and aged (STA) Incoloy 909 superalloy to evaluate the phases present using optical, SEM, TEM and differential scanning calorimetry. Comparison is made where possible with non-standard STA analyses reported in the literature. In the STA condition, the main phase present besides the γ matrix was a deliberately produced Laves phase to control grain growth. Increasing the solution temperature above that recommended for the alloy resulted in eventual solution of the Laves phase and concomitant grain growth. In the STA condition, in addition to the Laves phase, a copious precipitation of a γ′ phase (Ni3TiNb) was observed. In addition, a limited observation was made of the early stages of the transition of some of the γ′ phase to the ϵ phase for the over aged condition. There was no ϵ phase observed in the STA condition. A final observation was the presence of ‘black grain’ previously reported in the literature, in both the ST and STA conditions in the authors’ research. The present view is that the phenomenon is an etching artefact and not a genuine microstructural feature.
Effect of δ-ferrite, lead and sulphur on hot workability of austenitic stainless steels with solidification structure
Authors: Tehovnik F , Vodopivec F , Celin R , Arzenšek B , Gontarev J
Published: April 2011

The impurities sulphur, phosphorus, lead, bismuth, tin and antimony affect the hot workability of stainless steels. In this study, the authors show that sulphur and lead segregate to phase and solidification grain boundaries, where cracks appear during hot deformation. The workability was tested by the hot rolling and hot bending of industrial and laboratory steels.
Analytical characterisation of oxide dispersion strengthened steels for fusion reactors
Authors: de Castro V , Lozano-Perez S , Marquis E A , Auger M A , Leguey T , Pareja R
Published: April 2011

Reduced activation ferritic/martensitic and ferritic steels strengthened by a dispersion of oxide nanoparticles have been considered viable structural materials for fusion applications above 550°C. However, the microstructural stability and mechanical behaviour of these steels subjected to the aggressive operating conditions of these reactors are not well known. An accelerated development of these materials is crucial if they are going to be used in future power reactors. Then, it is indispensable to understand their atomic scale evolution under high temperature and irradiation conditions. The present paper reviews how the combination of transmission electron microscopy and atom probe tomography has been successfully applied for the characterisation of these steels at the near atomic scale, to reveal the nanoparticle structure, grain boundary chemistry and void distribution.
Three-dimensional atomic scale analysis of microstructures formed in high strength steels
Authors: Timokhina I B , Xiong X Y , Beladi H , Mukherjee S , Hodgson P D
Published: April 2011

The microstructures of steels consisting of ferrite (steel 1) and bainite (steel 2) were characterised using atom probe tomography. The microstructural features, such as formation of Nb–C clusters in steel 1 fine Fe–C particles, were observed.
Effects of friction stir welding and post-weld annealing on nanostructured ferritic alloy
Authors: Etienne A , Cunningham N J , Wu Y , Odette G R
Published: April 2011

Nanostructured ferritic alloys (NFAs) show great promise for use in high temperature energy systems, especially advanced fission and future fusion reactors. NFAs must be joined by solid state methods, such as friction stir welding (FSW), which is the focus of the present research. We address the key question on the effect of FSW on the ultrahigh density of nanoscale features (NFs) that imbue NFAs with their outstanding properties, including remarkable resistance to radiation damage. Atom probe tomography (APT) measurements suggest that the number densities N of the NFs are qualitatively similar before and after FSW, but they appear to be redistributed, resulting in a high degree of alignment along boundary and dislocation structures. The possibility of reprecipitating NFs during 1150°C–3 h anneals was also explored. However, the data show that both N and microhardness are lower after annealing the FSW alloy. Several limitations of the APT characterisation method are also discussed.
CD300a is expressed on human B cells, modulates BCR-mediated signaling, and its expression is down-regulated in HIV infection
Authors: Silva Rodolfo , Moir Susan , Kardava Lela , Debell Karen , Simhadri Venkateswara R. , Ferrando-Martínez Sara , Leal Manuel , Peña José , Coligan John E. , Borrego Francisco
Published: April 2011

The immunomodulatory receptor CD300a is expressed on human B cells. Naive B cells express very low levels of this receptor, whereas memory B cells and plasmablasts/cells express variable levels of CD300a. Germinal center B cells are negative for CD300a expression. Stimulation of naive B cells via B-cell receptor (BCR) and Toll-like receptor 9, along with T-cell help, failed to up-regulate CD300a cell surface expression despite the increased expression of the memory marker CD27 and the down-regulation of CD305. However, Toll-like receptor 9 stimulation alone significantly increased CD300a expression on memory B cells, whereas interleukin-4 and transforming growth factor-β1 act as negative regulators of CD300a expression on memory B cells. Coligation of BCR and CD300a inhibits Ca2+ mobilization and nuclear factor of activated T cell transcriptional activity evoked by BCR ligation alone. Suppression of CD300a expression in primary B cells with siRNA resulted in increased BCR-mediated proliferation, thereby confirming the inhibitory capacity of CD300a. Finally, we show that CD300a expression levels are significantly down-regulated in the circulating B cells of HIV-infected patients. Altogether, these data demonstrate a novel mechanism for suppressing the activity of B cells and suggest a potential role for CD300a in the B-cell dysfunction observed in HIV-induced immunodeficiency.
Cholesterol sequestration by nystatin enhances the uptake and activity of endostatin in endothelium via regulating distinct endocytic pathways
Authors: Chen Yang , Wang Shan , Lu Xinan , Zhang Haoran , Fu Yan , Luo Yongzhang
Published: April 2011

Specific internalization of endostatin into endothelial cells has been proved to be important for its biologic functions. However, the mechanism of endostatin internalization still remains elusive. In this study, we report for the first time that both caveolae/lipid rafts and clathrin-coated pits are involved in endostatin internalization. Inhibition of either the caveolae pathway or the clathrin pathway with the use of chemical inhibitors, small interfering RNAs, or dominant-negative mutants alters endostatin internalization in vitro. Intriguingly, cholesterol sequestration by nystatin, a polyene antifungal drug, significantly enhances endostatin uptake by endothelial cells through switching endostatin internalization predominantly to the clathrin-mediated pathway. Nystatin-enhanced internalization of endostatin also increases its inhibitory effects on endothelial cell tube formation and migration. More importantly, combined treatment with nystatin and endostatin selectively enhances endostatin uptake and biodistribution in tumor blood vessels and tumor tissues but not in normal tissues of tumor-bearing mice, ultimately resulting in elevated antiangiogenic and antitumor efficacies of endostatin in vivo. Taken together, our data show a novel mechanism of endostatin internalization and support the potential application of enhancing the uptake and therapeutic efficacy of endostatin via regulating distinct endocytic pathways with cholesterol-sequestering agents.
Northern blotting analysis of microRNAs, their precursors and RNA interference triggers
Authors: Koscianska Edyta , Starega-Roslan Julia , Sznajder Lukasz J , Olejniczak Marta , Galka-Marciniak Paulina , Krzyzosiak Wlodzimierz J
Published: April 2011

Background

Numerous microRNAs (miRNAs) have heterogeneous ends resulting from imprecise cleavages by processing nucleases and from various non-templated nucleotide additions. The scale of miRNA end-heterogeneity is best shown by deep sequencing data revealing not only the major miRNA variants but also those that occur in only minute amounts and are unlikely to be of functional importance. All RNA interference (RNAi) technology reagents that are expressed and processed in cells are also exposed to the same machinery generating end-heterogeneity of the released short interfering RNAs (siRNAs) or miRNA mimetics.

Results

In this study we have analyzed endogenous and exogenous RNAs in the range of 20-70 nt by high-resolution northern blotting. We have validated the results obtained with northern blotting by comparing them with data derived from miRNA deep sequencing; therefore we have demonstrated the usefulness of the northern blotting technique in the investigation of miRNA biogenesis, as well as in the characterization of RNAi technology reagents.

Conclusions

The conventional northern blotting enhanced to high resolution may be a useful adjunct to other miRNA discovery, detection and characterization methods. It provides quantitative data on distribution of major length variants of abundant endogenous miRNAs, as well as on length heterogeneity of RNAi technology reagents expressed in cells.
Production and partial purification of membrane proteins using a liposome-supplemented wheat cell-free translation system
Authors: Nozawa Akira , Ogasawara Tomio , Matsunaga Satoko , Iwasaki Takahiro , Sawasaki Tatsuya , Endo Yaeta
Published: April 2011

Background

Recently, some groups have reported on cell-free synthesis of functional membrane proteins (MPs) in the presence of exogenous liposomes (liposomes). Previously, we reported synthesis of a functional AtPPT1 plant phosphate transporter that was associated with liposomes during translation. However, it is unclear whether or not lipid/MP complex formation is common to all types of MPs in the wheat cell-free system.

Results

AtPPT1 was synthesized using a wheat cell-free system with or without liposomes. AtPPT1 synthesized with liposomes showed high transport activity, but the activity of AtPPT1 synthesized without liposomes was less than 10% activity of that with liposomes. To test whether co-translational association with liposomes is observed in the synthesis of other MPs, we used 40 mammalian MPs having one to 14 transmembrane domains (TMDs) and five soluble proteins as a control. The association rate of all 40 MPs into liposomes was more than 40% (mean value: 59%), while that of the five soluble proteins was less than 20% (mean value: 12%). There were no significant differences in association rate among MPs regardless of the number of TMDs and synthesis yield. These results indicate that the wheat cell-free system is a highly productive method for lipid/MP complex formation and is suitable for large-scale preparation. The liposome association of green fluorescent protein (GFP)-fusion MPs were also tested and recovered as lipid/MP complex after floatation by Accudenz density gradient ultracentrifugation (DGU). Employment of GFP-MPs revealed optimal condition for Accudenz floatation. Using the optimized Accudenz DGU condition, P2RX4/lipid complexes were partially purified and detected as a major band by Coomassie Brilliant Blue (CBB)-staining after SDS-PAGE.

Conclusion

Formation of lipid/AtPPT1 complex during the cell-free synthesis reaction is critical for synthesis of a functional MP. The lipid/MP complex during the translation was observed in all 40 MPs tested. At least 29 MPs, as judged by their higher productivity compared to GFP, might be suitable for a large-scale preparation. MPs synthesized by this method form lipid/MP complexes, which could be readily partially purified by Accudenz DGU. Wheat cell-free protein synthesis in the presence of liposomes will be a useful method for preparation of variety type of MPs.
Elevated expression of CDK4 in lung cancer
Authors: Wu Aibing , Wu Bin , Guo Jinsong , Luo Weiren , Wu Dong , Yang Huiling , Zhen Yan , Yu Xiaoli , Wang Hao , Zhou Ying , Liu Zhen , Fang Weiyi , Yang Zhixiong
Published: April 2011

Background

The aim of the present study was to analyze the expression of Cyclin-dependent kinase 4 (CDK4) in lung cancer and its correlation with clinicopathologic features. Furthermore, the involvement of CDK4-mediated cell cycle progression and its molecular basis were investigated in the pathogenesis of lung cancer.

Methods

Using immunohistochemistry analysis, we analyzed CDK4 protein expression in 89 clinicopathologically characterized lung cancer patients (59 males and 30 females) with ages ranging from 36 to 78 years and compared them to 23 normal lung tissues. Cases with cytoplasmic and nuclear CDK4 immunostaining score values greater than or equal to 7 were regarded as high expression while scores less than 7 were considered low expression. The correlation between the expression level of CDK4 and clinical features was analyzed. Furthermore, we used lentiviral-mediated shRNA to suppress the expression of CDK4 and investigate its function and molecular mechanism for mediating cell cycle progression.

Results

The expression level of CDK4 protein was significantly increased in lung cancer tissues compared to normal tissues (P < 0.001). In addition, high levels of CDK4 protein were positively correlated with the status of pathology classification (P = 0.047), lymph node metastasis (P = 0.007), and clinical stage (P = 0.004) of lung cancer patients. Patients with higher CDK4 expression had a markedly shorter overall survival time than patients with low CDK4 expression. Multivariate analysis suggested the level of CDK4 expression was an independent prognostic indicator (P < 0.001) for the survival of patients with lung cancer. Use of lentiviral-mediated shRNA to inhibit the expression of CDK4 in lung cancer cell line A549 not only inhibited cell cycle progression, but also dramatically suppressed cell proliferation, colony formation, and migration. Furthermore, suppressing CDK4 expression also significantly elevated the expression of cell cycle regulator p21

Conclusion

Overexpressed CDK4 is a potential unfavorable prognostic factor and mediates cell cycle progression by regulating the expression of p21 in lung cancer
Gene therapy with tumor-specific promoter mediated suicide gene plus IL-12 gene enhanced tumor inhibition and prolonged host survival in a murine model of Lewis lung carcinoma
Authors: Xu Yu , Hou Jinxuan , Liu Zhengchun , Yu Haijun , Sun Wenjie , Xiong Jie , Liao Zhengkai , Zhou Fuxiang , Xie Conghua , Zhou Yunfeng
Published: April 2011

Background

Gene therapy is a promising therapeutic approach for cancer. Targeted expression of desired therapeutic proteins within the tumor is the best approach to reduce toxicity and improve survival. This study is to establish a more effective and less toxic gene therapy of cancer.

Methods

Combined gene therapy strategy with recombinant adenovirus expressing horseradish peroxidase (HRP) mediated by human telomerase reverse transcriptase (hTERT) promoter (AdhTERTHRP) and murine interleukin-12 (mIL-12) under the control of Cytomegalovirus (CMV) promoter (AdCMVmIL-12) was developed and evaluated against Lewis lung carcinoma (LLC) both in vivo and in vitro. The mechanism of action and systemic toxicities were also investigated.

Results

The combination of AdhTERTHRP/indole-3-acetic acid (IAA) treatment and AdCMVmIL-12 resulted in significant tumor growth inhibition and survival improvement compared with AdhTERTHRP/IAA alone (tumor volume, 427.4 ± 48.7 mm3
vs 581.9 ± 46.9 mm3, p = 0.005 on day 15; median overall survival (OS), 51 d vs 33 d) or AdCMVmIL-12 alone (tumor volume, 362.2 ± 33.8 mm3
vs 494.4 ± 70.2 mm3, p = 0.046 on day 12; median OS, 51 d vs 36 d). The combination treatment stimulated more CD4+ and CD8+ T lymphocyte infiltration in tumors, compared with either AdCMVmIL-12 alone (1.3-fold increase for CD4+ T cells and 1.2-fold increase for CD8+ T cells, P < 0.01) or AdhTERTHRP alone (2.1-fold increase for CD4+ T cells and 2.2-fold increase for CD8+ T cells, P < 0.01). The apoptotic cells in combination group were significantly increased in comparison with AdCMVmIL-12 alone group (2.8-fold increase, P < 0.01) or AdhTERTHRP alone group (1.6-fold increase, P < 0.01). No significant systematic toxicities were observed.

Conclusions

Combination gene therapy with AdhTERTHRP/IAA and AdCMVmIL-12 could significantly inhibit tumor growth and improve host survival in LLC model, without significant systemic adverse effects.
Truncating the i-leader open reading frame enhances release of human adenovirus type 5 in glioma cells
Authors: van den Hengel Sanne K , de Vrij Jeroen , Uil Taco G , Lamfers Martine L , Sillevis Smitt Peter AE , Hoeben Rob C
Published: April 2011

Background

The survival of glioma patients with the current treatments is poor. Early clinical trails with replicating adenoviruses demonstrated the feasibility and safety of the use of adenoviruses as oncolytic agents. Antitumor efficacy has been moderate due to inefficient virus replication and spread. Previous studies have shown that truncation of the adenovirus i-leader open reading frame enhanced cytopathic activity of HAdV-5 in several tumor cell lines. Here we report the effect of an i-leader mutation on the cytopathic activity in glioma cell lines and in primary high-grade glioma cell cultures.

Results

A mutation truncating the i-leader open reading frame was created in a molecular clone of replication-competent wild-type HAdV-5 by site-directed mutagenesis. We analyzed the cytopathic activity of this RL-07 mutant virus. A cell-viability assay showed increased cytopathic activity of the RL-07 mutant virus on U251 and SNB19 glioma cell lines. The plaque sizes of RL-07 on U251 monolayers were seven times larger than those of isogenic control viruses. Similarly, the cytopathic activity of the RL-07 viruses was strongly increased in six primary high-grade glioma cell cultures. In glioma cell lines the RL-07 virus was found to be released earlier into the culture medium. This was not due to enhanced viral protein synthesis, as was evident from equivalent E1A, Fiber and Adenovirus Death Protein amounts, nor to higher virus yields.

Conclusion

The cytopathic activity of replicating adenovirus in glioblastoma cells is increased by truncating the i-leader open reading frame. Such mutations may help enhancing the antitumor cytopathic efficacy of oncolytic adenoviruses in the treatment of glioblastoma.
(−)-Pentazocine Induces Visceral Chemical Antinociception, but not Thermal, Mechanical, or Somatic Chemical Antinociception, in μ-Opioid Receptor Knockout Mice
Authors: Ide Soichiro , Minami Masabumi , Uhl George R , Satoh Masamichi , Sora Ichiro , Ikeda Kazutaka
Published: April 2011

Background:

(−)-Pentazocine has been hypothesized to induce analgesia via the κ-opioid (KOP) receptor, although the involvement of other opioid receptor subtypes in the effects of pentazocine remains unknown. In this study, we investigated the role of the μ-opioid (MOP) receptor in thermal, mechanical, and chemical antinociception induced by (−)-pentazocine using MOP receptor knockout (MOP-KO) mice.

Results:

(−)-Pentazocine-induced thermal antinociception, assessed by the hot-plate and tail-flick tests, was significantly reduced in heterozygous and abolished in homozygous MOP-KO mice compared with wildtype mice. The results obtained from the (−)-pentazocine-induced mechanical and somatic chemical antinociception experiments, which used the hind-paw pressure and formalin tests, were similar to the results obtained from the thermal antinociception experiments in these mice. However, (−)-pentazocine retained its ability to induce significant visceral chemical antinociception, assessed by the writhing test, in homozygous MOP-KO mice, an effect that was completely blocked by pretreatment with nor-binaltorphimine, a KOP receptor antagonist. In vitro binding and cyclic adenosine monophosphate assays showed that (−)-pentazocine possessed higher affinity for KOP and MOP receptors than for δ-opioid receptors.

Conclusions:

The present study demonstrated the abolition of the thermal, mechanical, and somatic chemical antinociceptive effects of (−)-pentazocine and retention of the visceral chemical antinociceptive effects of (−)-pentazocine in MOP-KO mice. These results suggest that the MOP receptor plays a pivotal role in thermal, mechanical, and somatic chemical antinociception induced by (−)-pentazocine, whereas the KOP receptor is involved in visceral chemical antinociception induced by (−)-pentazocine.