bluuebunny/crossref_metadata_2025 huggingface dataset:
Web‐based Structured Hypermedia Algorithm Explanation system
Authors: Shakshuki Elhadi , Kerren Andreas , Müldner Tomasz
Published: September 2007

Purpose

The purpose of this paper is to present the development of a system called Structured Hypermedia Algorithm Explanation (SHALEX), as a remedy for the limitations existing within the current traditional algorithm animation (AA) systems. SHALEX provides several novel features, such as use of invariants, reflection of the high‐level structure of an algorithm rather than low‐level steps, and support for programming the algorithm in any procedural or object‐oriented programming language.

Design/methodology/approach

By defining the structure of an algorithm as a directed graph of abstractions, algorithms may be studied top‐down, bottom‐up, or using a mix of the two. In addition, SHALEX includes a learner model to provide spatial links, and to support evaluations and adaptations.

Findings

Evaluations of traditional AA systems designed to teach algorithms in higher education or in professional training show that such systems have not achieved many expectations of their developers. One reason for this failure is the lack of stimulating learning environments which support the learning process by providing features such as multiple levels of abstraction, support for hypermedia, and learner‐adapted visualizations. SHALEX supports these environments, and in addition provides persistent storage that can be used to analyze students' performance. In particular, this storage can be used to represent a student model that supports adaptive system behavior.

Research limitations/implications

SHALEX is being implemented and tested by the authors and a group of students. The tests performed so far have shown that SHALEX is a very useful tool. In the future additional quantitative evaluation is planned to compare SHALEX with other AA systems and/or the concept keyboard approach.

Practical implications

SHALEX has been implemented as a web‐based application using the client‐server architecture. Therefore students can use SHALEX to learn algorithms both through distance education and in the classroom setting.

Originality/value

This paper presents a novel algorithm explanation system for users who wish to learn algorithms.
An innovative web‐based approach for study skills development in higher education
Authors: Bermingham Caitriona , Mahdi Abdulhussain E.
Published: September 2007

Purpose

It is recognised that students in higher education need to acquire and develop effective study and transferable skills in order to be successful in their study and beyond. The purpose of this paper is to describe a new custom‐built learning content management system (LCMS), which renders intelligent tutoring modules for the provision of study skills training, with emphasis on the educational pedagogies used by the system to deliver the training.

Design/methodology/approach

The system comprises two principal units; an administrator unit and a student‐user unit. The administrator unit is designed to enable authorised users with no prior knowledge of web application design and development to create and modify highly dynamic and engaging multimedia training modules. The student unit delivers highly interactive and user‐customised modules to help students develop their skills, using a pedagogical approach based on active, student‐centred and peer‐assisted learning.

Findings

The performance of the proposed system was subjected to a comprehensive test and evaluation process. General feedback from the users recruited to complete the subjective testing was very positive. It was generally acknowledged that the system was intuitive, the content well structured and delivered and the look and feel of the application aesthetically pleasing.

Originality/value

This paper highlights the use of and benefit of using technology to enhance student learning of study and other transferable skills. It also identifies the need to integrate proven educational pedagogies so as to enhance overall learning and demonstrates how to incorporate these approaches in an LCMS.
Sport and power: globalization and merchandizing in the soccer world
Authors: Madeiro Gustavo
Published: September 2007

Purpose

Management ideology is spreading everywhere. Not long ago, it was restricted to market enterprises, which methods, values, and goals now predominate also in other fields. The purpose of this paper is to discuss the changes that occurred in the arena of football by the construction of a worldwide field and by the creation of an international market.

Design/methodology/approach

This paper discusses the force relations among the actors in the football's field, of which analysis is based on a dialogue between Pierre Bourdieu's notion of social fields and Furtado's centre‐peripheric theory. Also, the Bosman arrest and Charleroi case are taken as keystone events in the establishment of a capitalistic football market.

Findings

By the history of general capitalism development, one finds a process of liberalization of the sport's production factors (the players), as well as the loss of centralized power by the decline of Fédération Internationale de Football Association and the tendency towards the monopolization of the this sport on a world professional level – concentration of power in several key clubs. In this sense, an increasingly dominant intervention of European clubs in the poorer countries' markets can thus be envisaged.

Originality/value

The discussion of a cultural organization's field is often forgotten in the management debates, and seems to be reserved for sociologists and anthropologists. But, it is precisely this sheep‐herding management method – and its widely dispersed ideology – that is the changing instrument of this aspect of the field. The paper underlines the meeting between the theories which prove themselves productive concerning this subject.
Alfred D. Chandler Jr – who raise the visible hands of wealthy nations?
Authors: Chopin David
Published: September 2007

Purpose

This paper aims to present Alfred Chandler's works as one of the main authors to face the business and society field. It synthesizes his conceptual achievements though national capitalisms that he has identified.

Design/methodology/approach

Alfred Chandler's works are summarized analytically. His historic comparative method pinpointed different types of capitalism through managerial hierarchy that enabled firms. National leaders were grounded in their society, and Chandler's works explain economic dominance of big business by organization form they developed.

Findings

Over his intellectual career, Alfred Chandler has conceptualized different types of capitalism related to national business history: the process of visible hands internalization, managerial hierarchy, organizational capability and path of learning; that reflect, respectively, USA, British, German and Japanese type of capitalism according to their own business history. History, society matters, due to Alfred Chandler's considerable influence could open alternative and valuable ways for management and economic studies.

Originality/value

This paper presents management and economic theoretical implications of a prominent leader of the business history field. Arguing why Alfred Chandler's concepts are unique and have opened the crucial importance of implicating management studies to society matters. These preoccupations constitute also – this paper would stress on this point – the core of Society and Business field.
Converging instructional technology and critical intercultural pedagogy in teacher education
Authors: Pittman Joyce
Published: September 2007

Purpose

This paper aims to postulate an emerging unified cultural‐convergence framework to converge the delivery of instructional technology and intercultural education (ICE) that extends beyond web‐learning technologies to inculcate inclusive pedagogy in teacher education.

Design/methodology/approach

The paper explores the literature and a tech‐infused multicultural learning community to identify what a unified cultural‐convergence theory might consist of and how it could be shaped to align instructional technology and critical ICE in teacher education. Four questions are asked: What key learning do these two disciplines make available to teachers and educators that are essential for today's highly diverse, complex classrooms? What can we draw from a convergence of multiculturalism and global education that will help us derive a new theoretical understanding of a unified cultural‐convergence theory to connect IT and ICE education? What knowledge, skills and dispositions comprise three essential components of this literature synthesis? How can this new unified cultural‐convergence theory and relevant components be taught, practiced, and measured? The paper contains several tables, figures and over 50 sources in the research bibliography that were selected from a review and analysis of 100 documents.

Findings

The paper discovered instructional technology and intercultural educators employed web‐learning technologies in very similar ways to position critical ICE strategies into programs or courses in teacher education. The learning technologies models that were attempting to support multicultural education (MCE)/ICE and IT education included corporate, universities, research centers, schools, and government partners. Reportedly, according to the research, teacher educators in IT education do not employ instructional technology practices that differ from practices that are needed or valued by MCE educators to merge critical intercultural structures into teacher education through web‐learning technologies. This was good news as the researcher moves toward a recommendation for a research agenda that could be shared by educators from the two groups.

Research limitations/implications

The paper is limited to literature reviews, reports, and evaluation documents.

Originality/value

The paper offers implications for curriculum development in educational technology and MCE using ICTs
How to manage multiple faculty identifications during change
Authors: Harvey Michael , Novicevic Milorad M. , Zikic Jelena , Ready Kathryn
Published: September 2007

Purpose

The purpose of this conceptual paper is to examine multiple‐faculty identifications to propose a differentiated management system that can be effective in today's changing educational environment.

Design/methodology/approach

The paper examines multiple‐faculty identifications that faculty members have with their institution from an identity theory perspective with the objective of developing an appropriate typology of faculty members.

Findings

After assessing key faculty needs underlying each form of faculty identification within their institution, the authors develop a differentiated management model that can be used by administrators when pursuing change initiatives in their institutions.

Originality/value

The practical implementation of the proposed model can yield coherent change in institutions of higher education through the administrative efforts of building collective competency.
Exercises in tourism empowerment practice
Authors: Timmerman John E. , Lytle Richard S.
Published: September 2007

Purpose

The paper's purpose is to provide background and practical exercises for management to gain a perspective on the nature of true employee empowerment.

Design/methodology/approach

After a brief overview of the nature of empowerment, a series to training exercises offers insight into how employee empowerment in the tourism industry can create deeper investment in the corporate mission and greater customer service. The exercises also examine approaches for management to avoid.

Findings

Employee empowerment results from recognizing the employee's ability to be organization's eyes and ears.

Originality/value

This discussion and set of exercises provides management with the opportunity to test their instincts against realistic situations of employee empowerment in the context of service failure.
Executive training exercises in non‐performance and attrition charges in the hospitality industry
Authors: Toh Rex S. , Yates Barbara M. , DeKay Frederick
Published: September 2007

Purpose

The aim of the paper is to help graduate students in the area of hospitality management to understand and deal with non‐performance charges and attrition issues.

Design/methodology/approach

The paper uses case studies to illustrate the issues that must be resolved.

Findings

There are many ways to look at issues – from the hotel's perspective, from the customer's viewpoint, and from an independent observer's position.

Originality/value

This training exercise highlights the complicated issues surrounding non‐performance charges and attrition issues, and suggests ways in which they can be fairly resolved to the mutual satisfaction of all parties to preserve goodwill all around.
Management learning exercise and trainer's note for market segmentation in tourism
Authors: Dolnicar Sara
Published: September 2007

Purpose

This paper aims to show how researchers can develop learning exercises for training analysts and executives in market segmentation techniques.

Design/methodology/approach

The empirical example of a tour operator specializing in adventure tourism is used as an illustration. Segments are constructed on the basis of tourists' stated willingness to pay a price premium for certain aspects of the tour. Stability analysis is conducted to choose the number of clusters, topology representing networks are used to construct segments and Bonferroni‐corrected χ2 tests provide insight into the external validity of segments.

Findings

Four market segments are constructed which differ significantly with respect to external variables.

Research limitations/implications

Market segmentation can be used by any entity in the tourism industry to select a suitable part of the entire market, customize the tourism service to suit such a segment, and spend marketing budget more efficiently by using communication channels and advertising messages most effective for the selected segment.

Originality/value

Market segmentation provides managers with insight into market structure. Knowledge about the market structure, in turn, is the basis of successful strategic planning. While the concept of segmentation is not new, each application is unique to its context. The present paper focuses on price premium segments in the adventure tourism context.
Executive learning exercise and trainer's notes for importance‐performance analysis (IPA)
Authors: Huan Tzung‐Cheng (T.C.) , Beaman Jay
Published: September 2007

Purpose

Conceptual aspects of this research aim to review issues and to introduce new ways to employ importance‐performance analysis (IPA), also called action‐grid analysis (AGA), in formulating valid research. The purpose of the exercises is facilitating understanding how a variety of matters are important for research being valid.

Design/methodology/approach

IPA/AGA, different types of IPA/AGA, and validity issues for these are introduced. Pursuing two types of IPA/AGA, based on different assumptions and thus distinct validity criteria, reinforces the need for new thinking regarding valid applications of IPA/AGA. Practically oriented training exercises reinforce understanding concepts introduced. Possible answers to exercises encourage thinking about matters that directly affect validity of actual research.

Findings

Unless IPA/AGA research is well conceived, properly executed, and soundly analysed, implications derived may be misleading. Training exercises show the reader values and pitfalls of considering IPA/AGA in formulating practically oriented research.

Research limitations/implications

A limitation of the research is that detail results are only presented for two of at least five types of IPA/AGA.

Originality/value

This paper contributes to the overall understanding of the valid use of IPA/AGA as a tool in research. The paper also facilitates using IPA/AGA in teaching about research.
Fold assessment for comparative protein structure modeling
Authors: Melo Francisco , Sali Andrej
Published: September 2007

Accurate and automated assessment of both geometrical errors and incompleteness of comparative protein structure models is necessary for an adequate use of the models. Here, we describe a composite score for discriminating between models with the correct and incorrect fold. To find an accurate composite score, we designed and applied a genetic algorithm method that searched for a most informative subset of 21 input model features as well as their optimized nonlinear transformation into the composite score. The 21 input features included various statistical potential scores, stereochemistry quality descriptors, sequence alignment scores, geometrical descriptors, and measures of protein packing. The optimized composite score was found to depend on (1) a statistical potential z‐score for residue accessibilities and distances, (2) model compactness, and (3) percentage sequence identity of the alignment used to build the model. The accuracy of the composite score was compared with the accuracy of assessment by single and combined features as well as by other commonly used assessment methods. The testing set was representative of models produced by automated comparative modeling on a genomic scale. The composite score performed better than any other tested score in terms of the maximum correct classification rate (i.e., 3.3% false positives and 2.5% false negatives) as well as the sensitivity and specificity across the whole range of thresholds. The composite score was implemented in our program MODELLER‐8 and was used to assess models in the MODBASE database that contains comparative models for domains in approximately 1.3 million protein sequences.
Folding and stability of the isolated Greek key domains of the long‐lived human lens proteins γD‐crystallin and γS‐crystallin
Authors: Mills Ishara A. , Flaugh Shannon L. , Kosinski‐Collins Melissa S. , King Jonathan A.
Published: September 2007

The transparency of the eye lens depends on the high solubility and stability of the lens crystallin proteins. The monomeric γ‐crystallins and oligomeric β‐crystallins have paired homologous double Greek key domains, presumably evolved through gene duplication and fusion. Prior investigation of the refolding of human γD‐crystallin revealed that the C‐terminal domain folds first and nucleates the folding of the N‐terminal domain. This result suggested that the human N‐terminal domain might not be able to fold on its own. We constructed and expressed polypeptide chains corresponding to the isolated N‐ and C‐terminal domains of human γD‐crystallin, as well as the isolated domains of human γS‐crystallin. Both circular dichroism and fluorescence spectroscopy indicated that the isolated domains purified from Escherichia coli were folded into native‐like monomers. After denaturation, the isolated domains refolded efficiently at pH 7 and 37°C into native‐like structures. The in vitro refolding of all four domains revealed two kinetic phases, identifying partially folded intermediates for the Greek key motifs. When subjected to thermal denaturation, the isolated N‐terminal domains were less stable than the full‐length proteins and less stable than the C‐terminal domains, and this was confirmed in equilibrium unfolding/refolding experiments. The decrease in stability of the N‐terminal domain of human γD‐crystallin with respect to the complete protein indicated that the interdomain interface contributes of 4.2 kcal/mol to the overall stability of this very long‐lived protein.
The structural topology of wild‐type phospholamban in oriented lipid bilayers using 15N solid‐state NMR spectroscopy
Authors: Abu‐Baker Shadi , Lu Jun‐Xia , Chu Shidong , Shetty Kiran K. , Gor′kov Peter L. , Lorigan Gary A.
Published: September 2007

For the first time, 15N solid‐state NMR experiments were conducted on wild‐type phospholamban (WT‐PLB) embedded inside mechanically oriented phospholipid bilayers to investigate the topology of its cytoplasmic and transmembrane domains. 15N solid‐state NMR spectra of site‐specific 15N‐labeled WT‐PLB indicate that the transmembrane domain has a tilt angle of 13° ± 6° with respect to the POPC (1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐phosphocholine) bilayer normal and that the cytoplasmic domain of WT‐PLB lies on the surface of the phospholipid bilayers. Comparable results were obtained from site‐specific 15N‐labeled WT‐PLB embedded inside DOPC/DOPE (1,2‐dioleoyl‐sn‐glycero‐3‐phosphocholine/1,2‐dioleoyl‐sn‐glycero‐3‐phosphoethanolamine) mechanically oriented phospholipids' bilayers. The new NMR data support a pinwheel geometry of WT‐PLB, but disagree with a bellflower structure in micelles, and indicate that the orientation of the cytoplasmic domain of the WT‐PLB is similar to that reported for the monomeric AFA‐PLB mutant.
The intrinsically disordered TC‐1 interacts with Chibby via regions with high helical propensity
Authors: Gall Chris , Xu Hanyu , Brickenden Anne , Ai Xuanjun , Choy Wing Yiu
Published: September 2007

Thyroid cancer 1 (TC‐1) is a 106‐residue naturally disordered protein that has been found to associate with thyroid, gastric, and breast cancers. Recent studies showed that the protein functions as a positive regulator in the Wnt/β‐catenin signaling pathway, a pathway that is known to play essential roles in developmental processes and causes tumor formation when misregulated. By competing with β‐catenin for binding to Chibby (Cby), a conserved nuclear protein that antagonizes the β‐catenin–mediated transcriptions, TC‐1 up‐regulates a number of β‐catenin target genes that are known to be involved in the aggressive behavior of cancers. In order to gain a molecular understanding of the role TC‐1 plays in regulating the Wnt/β‐catenin signaling pathway, detailed structural studies of the protein and its interaction with Cby are essential. In this work, we used nuclear magnetic resonance (NMR) spectroscopy to elucidate the structure of TC‐1 and its interaction with Cby. Our results indicate that even though TC‐1 is naturally disordered, the protein adopts fairly compact conformations under nondenaturing conditions. Chemical shift analysis and relaxation measurements show that three regions (D44‐R53, K58‐A64, and D73‐T88) with high‐helical propensity are present in the C‐terminal portion of TC‐1. Upon addition of Cby, significant broadening of resonance signals derived from these helical regions of TC‐1 was observed. The result indicates that the intrinsically disordered TC‐1 interacts with Cby via its transient helical structure.
Engineering and rapid selection of a low‐affinity glucose/galactose‐binding protein for a glucose biosensor
Authors: Amiss Terry J. , Sherman Douglas B. , Nycz Colleen M. , Andaluz Sandra A. , Pitner J. Bruce
Published: September 2007

Periplasmic expression screening is a selection technique used to enrich high‐affinity proteins in Escherichia coli. We report using this screening method to rapidly select a mutated D‐glucose/D‐galactose‐binding protein (GGBP) having low affinity to glucose. Wild‐type GGBP has an equilibrium dissociation constant of 0.2 μM and mediates the transport of glucose within the periplasm of E. coli. The protein undergoes a large conformational change on binding glucose and, when labeled with an environmentally sensitive fluorophore, GGBP can relay glucose concentrations, making it of potential interest as a biosensor for diabetics. This use necessitates altering the glucose affinity of GGBP, bringing it into the physiologically relevant range for monitoring glucose in humans (1.7–33 mM). To accomplish this a focused library was constructed using structure‐based site‐saturation mutagenesis to randomize amino acids in the binding pocket of GGBP at or near direct H‐bonding sites and screening the library within the bacterial periplasm. After selection, equilibrium dissociation constants were confirmed by glucose titration and fluorescence monitoring of purified mutants labeled site‐specifically at E149C with the fluorophore IANBD (N,N′‐dimethyl‐N‐(iodoacetyl)‐N′‐(7‐nitrobenz‐2‐oxa‐1,3‐diazol‐4‐yl)ethylene‐diamine). The screening identified a single mutation A213R that lowers GGBP glucose affinity 5000‐fold to 1 mM. Computational modeling suggested the large decrease in affinity was accomplished by the arginine side chain perturbing H‐bonding and increasing the entropic barrier to the closed conformation. Overall, these experiments demonstrate the ability of structure‐based site‐saturation mutagenesis and periplasmic expression screening to discover low‐affinity GGBP mutants having potential utility for measuring glucose in humans.
New protein fold revealed by a 1.65 Å resolution crystal structure of Francisella tularensis pathogenicity island protein IglC
Authors: Sun Ping , Austin Brian P. , Schubot Florian D. , Waugh David S.
Published: September 2007

Francisella tularensis is a highly infectious Gram‐negative intracellular pathogen that causes the fulminating disease tularemia and is considered to be a potential bioweapon. F. tularensis pathogenicity island proteins play a key role in modulating phagosome biogenesis and subsequent bacterial escape into the cytoplasm of macrophages. The 23 kDa pathogenicity island protein IglC is essential for the survival and proliferation of F. tularensis in macrophages. Seeking to gain some insight into its function, we determined the crystal structure of IglC at 1.65 Å resolution. IglC adopts a β‐sandwich conformation that exhibits no similarity with any known protein structure.
Narrow‐band ultraviolet B phototherapy in patients with recalcitrant nodular prurigo
Authors: TAMAGAWA‐MINEOKA Risa , KATOH Norito , UEDA Eiichiro , KISHIMOTO Saburo
Published: September 2007

Management of nodular prurigo has been less than satisfactory. Conventional therapies such as systemic antihistamines and topical steroids have not been particularly successful. The effects of narrow‐band ultraviolet B (NB‐UVB) phototherapy in the treatment of various inflammatory dermatoses have been proven, however, no data exist on the efficacy and the duration of remission in NB‐UVB monotherapy for nodular prurigo. The aim of this study was to evaluate the effect of NB‐UVB phototherapy on recalcitrant nodular prurigo. NB‐UVB phototherapy was performed once a week on 10 patients with recalcitrant nodular prurigo. The initial dose was 0.4 J/cm2, and the dose was increased by 0.1 J/cm2 for each treatment. The treatment was performed until the eruption was almost clear. In each patient, a mean cumulative dose of 23.88 J/cm2 was applied over a mean of 24.3 irradiations. The mean maximum daily dose of ultraviolet B was 1.2 ± 0.4 J/cm2. NB‐UVB phototherapy notably improved the eruption of nodular prurigo in all patients. Follow up at 1 year revealed that only one patient had relapsed. The remaining nine patients continued to derive long‐term benefits. NB‐UVB phototherapy appears to be an effective treatment for recalcitrant nodular prurigo, offering long‐term benefits in the majority of those treated.
Lichenoid drug eruption of nails induced by propylthiouracil
Authors: SAITO Marumi , NAKAMURA Koichiro , KANEKO Fumio
Published: September 2007

We present the case of a patient who developed deformities of the fingernails and reddish nodules on the nail beds after administration of propylthiouracil (PTU) for 6 months to treat Grave's disease. Histological examination of the lesion revealed a lichenoid tissue reaction. After withdrawal of PTU, she noticed an improvement in the eruption and the growth of the nails. No recurrence of the eruption was detected after the withdrawal of PTU. Thus, we strongly suggest that this was a rare case of PTU‐induced lichenoid drug eruption of nail.
Nail discoloration occurring after 8 weeks of minocycline therapy
Authors: BAN Masanori , KITAJIMA Yasuo
Published: September 2007

Minocycline‐induced nail pigmentation is an uncommon side‐effect. It usually develops after years of the therapy, and coincides with other pigmented sites. We report a 73‐year‐old male and a 33‐year‐old female developing nail discoloration after 8 weeks of therapy of 100 mg minocycline twice daily. No other pigmentation was found elsewhere on the skin, mucous membranes, teeth or sclerae of them. Our cases demonstrate that nail pigmentation can occur after short‐term minocycline therapy, and propose the possibility that nail discoloration may precede other pigmentary changes.
Fusion of single‐photon emission computed tomography and computed tomography images of sentinel lymph nodes in extramammary Paget's disease of the scrotum
Authors: TSUJINO Yoshio , KUSATAKE Kenji , KANEKO Sakae , YAMAMOTO Yasushi , FURUMURA Minao , MORITA Eishin
Published: September 2007

We describe a new method for the fusion of single‐photon emission computed tomography (SPECT) and multidetector computed tomography (MDCT) images using an acrylic resin marker containing 99 m‐Tc phytate and viewing software (Fusion Viewer Version 1.0 for Windows). This method provided the fusion of SPECT and CT images in a short time and made it easy to identify the sentinel lymph nodes in the patient with extramammary Paget's disease of the scrotum.
Interdigital amelanotic spindle‐cell melanoma mimicking an inflammatory process due to dermatophytosis
Authors: DAINICHI Teruki , KOBAYASHI Chikashi , FUJITA Shohei , SHIRAMIZU Kei , ISHIKO Toshiyuki , KIRYU Hiromaro , URABE Kazunori , TSUNEYOSHI Masazumi , FURUE Masutaka
Published: September 2007

Herein, we report a rare case of amelanotic spindle‐cell melanoma on the interdigit of the left fifth toe of an 83‐year‐old woman. She also had tinea pedis on the same part for more than 2 years, and the part in which the tumor developed had been macerated and colonized with both Pseudomonas aeruginosa and methicillin‐resistant Staphylococcus aureus. Histopathologically, the biopsy specimen was indistinguishable from that of nonspecific inflammatory granulation. Two biopsies could not lead us to the correct diagnosis until the totally excised specimen was evaluated with immunohistochemical analysis including S‐100 and other melanocyte markers. The patient died with multiple metastases of the tumor 18 months after her first visit. This case suggests that refractory interdigital dermatophytoses should be treated by considering the possibility of concomitant malignant neoplasms, and immunohistochemical analysis is indispensable for differential diagnosis of malignant neoplasms suggesting nonspecific granulation.
Phosphorylated retinoid X receptor α loses its heterodimeric activity with retinoic acid receptor β
Authors: Yoshimura Kotaro , Muto Yoshinori , Shimizu Masahito , Matsushima‐Nishiwaki Rie , Okuno Masataka , Takano Yukihiko , Tsurumi Hisashi , Kojima Soichi , Okano Yukio , Moriwaki Hisataka
Published: September 2007

A malfunction in retinoid X receptor (RXR) α due to phosphorylation is associated with the development of hepatocellular carcinoma. However, the precise mechanisms by which phosphorylated RXRα loses its physiological function remain unclear. In the present study we examined whether phosphorylation of RXRα affects its dimeric activity. Fluorescence resonance energy transfer studies and immunoprecipitation assays showed that the physical interaction between RXRα and retinoic acid receptor β was impaired when 293T cells were transfected with phosphomimic mutant RXRα (T82D/S260D), whereas this interaction was activated at a level similar to wild‐type RXRα‐transfected cells when the cells were transfected with an unphosphorylated mutant RXRα (T82A/S260A). Treating the T82A/S260A‐transfected cells with retinoid resulted in a significant increase in the transcriptional activities of the retinoic acid receptor responsive element and RXR responsive element promoters, whereas these transcriptional activities did not increase in the T82D/S260D‐transfected cells. Transfection with T82A/S260A enhanced both the inhibition of cell growth and the induction of apoptosis caused by retinoid, although the T82D/S260D‐transfected cells lost their responsiveness to retinoid. Moreover, transfection with T82A/S260A caused an inhibition of cell growth and a reduction of colony‐forming ability in soft agar in HuH7 human hepatocellular carcinoma cells. These findings suggest that phosphorylation of RXRα abolishes its ability to form homodimers and heterodimers with RXR and retinoic acid receptor β, thus resulting in the loss of cell growth control and the acceleration of cancer development. In conclusion, the inhibition of RXRα phosphorylation and the restoration of its original function as a master regulator of nuclear receptors might therefore be an effective strategy for controlling cancer cell growth. (Cancer Sci 2007; 98: 1868–1874)
Inhibition of early preneoplastic events in the rat liver by the somatostatin analog lanreotide
Authors: Borbath Ivan , Leclercq Isabelle A. , Abarca‐Quinones Jorge , Desaeger Christine , Lebrun Valérie , Moulin Pierre , Sempoux Christine , Horsmans Yves
Published: September 2007

Hepatocellular carcinoma (HCC) is the third most common cause of cancer‐related death, and its incidence is increasing worldwide. Due to the known risk factors (mainly hepatitis B and C viruses), we believe there is a rationale for a chemopreventive approach to treat HCC. Here, based on described in vitro data, we evaluated the preventive effects of lanreotide, a somatostatin analog, on the induction of early carcinogenic events. We monitored preneoplastic foci induced by a two‐stage initiation/promotion model of hepatocarcinogenesis in male Wistar rats, using diethylnitrosamine and 2‐acetylaminofluorene. Lanreotide was given starting the day after the first diethylnitrosamine injection. By quantitative morphometry, we showed that lanreotide significantly decreases the size of induced preneoplastic foci. Analysis of proliferation and apoptosis assessed by immunohistochemistry, showed decreased proliferation and increased cell death in rats treated with lanreotide. As these events were associated with a significant decreased expression of the cell cycle regulator cyclin D1 and an increased expression of the cyclin‐dependent kinase inhibitor p27kip1 compared to the non‐treated group, it is tempting to speculate that these factors are involved in the favorable effect of lanreotide. In conclusion, lanreotide significantly decreases early carcinogenic transformation in a two‐step rat model. As lanreotide has a low toxicity profile, we believe it would be interesting to evaluate its effect in chemoprevention of HCC. (Cancer Sci 2007; 98: 1831–1839)
The fine needle aspiration appearances of Kikuchi’s lymphadenitis
Authors: Osborn M. , Aqel N. , Levine T. S.
Published: October 2007

Objective:  To describe the fine needle aspiration cytological appearances of Kikuchi’s lymphadenitis.

Methods:  Cytological review with histological correlation of all cases of Kikuchi’s disease (KD) in which there had been an antecedent fine needle aspirate of the involved lymph node prior to lymph node excision between 2001 and 2006.

Results:  Twelve cases of KD were identified in which cytological and histological material was available. In eight cases the original prospective diagnosis of necrotizing non‐granulomatous lymphadenitis consistent with KD had been suggested on the lymph node aspirate. Review of these cytological samples identified abundant extra‐ and intracellular apoptotic debris – the latter embedded in the cytoplasm of crescentic and phagocytic macrophages, set in a background reactive lymphoid population. Three of 12 cases were initially reported as in keeping with nonspecific reactive lymphadenopathy. Review identified intracellular apoptotic debris but no conspicuous extracellular nuclear debris. One case had originally been reported as possible non‐Hodgkin’s lymphoma. Histological review of the excised lymph nodes in all 12 cases showed the classical appearances of KD.

Conclusion:  The accurate diagnosis of KD on fine needle aspiration is possible given correct clinical data, an adequately sampled and well‐prepared specimen in which the characteristic intra‐ and extracellular apoptotic nuclear debris with admixed crescentic macrophages are identified on a reactive lymphoid background.
In vivo confocal laser scanning chromo‐endomicroscopy of colorectal neoplasia: changing the technological paradigm
Authors: Hurlstone D P , Tiffin N , Brown S R , Baraza W , Thomson M , Cross S S
Published: September 2007

Recently, miniaturization of a novel confocal laser endomicroscope (Optiscan Pty, Notting Hill, Victoria, Australia) has permitted functional integration into the distal tip of a conventional video colonoscope (Pentax EC3870K; Pentax, Tokyo, Japan) enabling imaging of the surface epithelium and the underlying lamina propria during ongoing video endoscopy. Using endomicroscopy and intravenous sodium fluorescein as a contrast agent, ‘virtual histology’ can be created, which allows visualization of both the surface epithelium, and some of the lamina propria (down to a quarter of a millimetre), including the microvasculature. Confocal endomicroscopy may have major implications in the future of colonoscopy as uniquely it allows in vivo diagnosis of colonic intraepithelial neoplasia and carcinoma enabling ‘smart’ biopsy targeting and hence potentially influencing ‘on table’ management decisions. Initial pilot data have now shown that confocal imaging in vivo using the newly developed EC3870K has high overall accuracy for the immediate diagnosis of intraepithelial neoplasia and carcinoma in sporadic screened cohorts, but also has a role in the detection of intraepithelial neoplasia detection in chronic ulcerative colitis cancer screening when used in conjunction with methylene blue chromoscopy. We discuss the current evidence in support of confocal endomicroscopy in the colorectum and explore the new diagnostic possibilities for this technology.
Cyclooxygenase‐2 expression correlates with phaeochromocytoma malignancy: evidence for a Bcl‐2‐dependent mechanism
Authors: Cadden I S , Atkinson A B , Johnston B T , Pogue K , Connolly R , McCance D , Ardill J E S , Russell C F , McGinty A
Published: October 2007

Aims:  Phaeochromocytomas are rare but potentially life‐threatening neuroendocrine tumours of the adrenal medulla or sympathetic nervous system ganglia. There are no histological features which reliably differentiate benign from malignant phaeochromocytomas. The aim of the study was to evaluate cyclooxygenase (COX)‐2 and Bcl‐2 as tissue‐based biomarkers of phaeochromocytoma prognosis.

Methods and results:  COX‐2 and Bcl‐2 expression were examined immunohistochemically in tissue from 41 sporadic phaeochromocytoma patients followed up for a minimum of 5 years after diagnosis. There was a statistically significant association between COX‐2 histoscore (intensity × proportion) and the development of tumour recurrence or metastases (P = 0.006). A significant relationship was observed between coexpression of COX‐2 and Bcl‐2 in the primary tumour and the presence of recurrent disease (P = 0.034). A highly significant association was observed between (i) tumour‐associated expression of these two oncoproteins (P = 0.001) and (ii) COX‐2 histoscore and the presence of Bcl‐2 expression (P = 0.002). COX regression analysis demonstrated no significant relationship between (i) the presence or absence of either COX‐2 or Bcl‐2 and patient survival or (ii) COX‐2 histoscore and patient survival.

Conclusions:  COX‐2 and Bcl‐2 may promote phaeochromocytoma malignancy, and these oncoproteins may be valuable surrogate markers of an aggressive tumour phenotype.
Malaria protection in β2‐microglobulin‐deficient mice lacking major histocompatibility complex class I antigens: essential role of innate immunity, including γδT cells
Authors: Taniguchi Tomoyo , Tachikawa Saoko , Kanda Yasuhiro , Kawamura Toshihiko , Tomiyama‐Miyaji Chikako , Li Changchun , Watanabe Hisami , Sekikawa Hiroho , Abo Toru
Published: October 2007

It is still controversial whether malaria protection is mediated by conventional immunity associated with T and B cells or by innate immunity associated with extrathymic T cells and autoantibody‐producing B cells. Given this situation, it is important to examine the mechanism of malaria protection in β2‐microglobulin‐deficient (β2m(–/–)) mice. These mice lack major histocompatibility complex class I and CD1d antigens, which results in the absence of CD8+ T cells and natural killer T (NKT) cells. When C57BL/6 and β2m(–/–) mice were injected with parasitized (Plasmodium yoelii 17XNL) erythrocytes, both survived from the infection and showed a similar level of parasitaemia. The major expanding T cells were NK1.1– αβΤ‐cell receptorint cells in both mice. The difference was a compensatory expansion of NK and γδT cells in β2m(–/–) mice, and an elimination experiment showed that these lymphocytes were critical for protection in these mice. These results suggest that malaria protection might be events of the innate immunity associated with multiple subsets with autoreactivity. CD8+ T and NKT cells may be partially related to this protection.
Natural killer T‐cell characterization through gene expression profiling: an account of versatility bridging T helper type 1 (Th1), Th2 and Th17 immune responses
Authors: Niemeyer Marcus , Darmoise Alexandre , Mollenkopf Hans‐Joachim , Hahnke Karin , Hurwitz Robert , Besra Gurdyal S. , Schaible Ulrich E. , Kaufmann Stefan H. E.
Published: October 2007

Natural killer T (NKT) cells constitute a distinct lymphocyte lineage at the interface between innate and adaptive immunity, yet their role in the immune response remains elusive. Whilst NKT cells share features with other conventional T lymphocytes, they are unique in their rapid, concomitant production of T helper type 1 (Th1) and Th2 cytokines upon T‐cell receptor (TCR) ligation. In order to characterize the gene expression of NKT cells, we performed comparative microarray analyses of murine resting NKT cells, natural killer (NK) cells and naïve conventional CD4+ T helper (Th) and regulatory T cells (Treg). We then compared the gene expression profiles of resting and alpha‐galactosylceramide (αGalCer)‐activated NKT cells to elucidate the gene expression signature upon activation. We describe here profound differences in gene expression among the various cell types and the identification of a unique NKT cell gene expression profile. In addition to known NKT cell‐specific markers, many genes were expressed in NKT cells that had not been attributed to this population before. NKT cells share features not only with Th1 and Th2 cells but also with Th17 cells. Our data provide new insights into the functional competence of NKT cells which will facilitate a better understanding of their versatile role during immune responses.
Side population cells expressing ABCG2 in human adult dental pulp tissue
Authors: Honda M. J. , Nakashima F. , Satomura K. , Shinohara Y. , Tsuchiya S. , Watanabe N. , Ueda M.
Published: October 2007

Aim  To investigate the presence of side population (SP) cells by the Hoechst exclusion method in human adult dental pulp tissue.

Methodology  Human adult dental pulp‐derived cells were generated from third molar teeth. The cells were stained with Hoechst 33342 and sorted into SP cells or non‐SP cells [main population (MP) cells]. Both cell types were compared with cell growth and RT–PCR analyses.

Results  SP cells that express ABCG2, Nestin, Notch‐1 and α‐smooth muscle actin were found at frequencies ranging from 0.67% to 1.02%. This SP profile disappeared in the presence of verapamil. These SP cells expressed dentine sialophosphoprotein and dentine matrix protein‐1 when cultured in osteogenic medium.

Conclusion  Human adult dental pulp tissue contains SP cells that differentiate into odontoblast‐like cells.
Bacterial penetration along different root canal filling materials in the presence or absence of smear layer
Authors: Saleh I. M. , Ruyter I. E. , Haapasalo M. , Ørstavik D.
Published: October 2007

Aim  To study the effect of the smear layer on the penetration of bacteria along different root canal filling materials and to examine the dentine/sealer and sealer/core material interfaces for the presence of bacteria.

Methodology  A total of 110 human root segments were instrumented to size 80 under irrigation with 1% sodium hypochlorite. Half of the roots were irrigated with a 5‐mL rinse of 17% EDTA. Roots with and without smear layer were filled with gutta‐percha (GP) and AH Plus sealer (AH), GP and Apexit sealer (AP), or RealSeal cones and sealer (RS). Following storage in humid conditions at 37 °C for 7 days, the specimens were mounted into a bacterial leakage test model for 135 days. Survival analyses were performed to calculate the median time of leakage and log‐rank test was used for pairwise comparisons of groups. The level of significance was set at P = 0.05. Selected specimens were longitudinally sectioned and inspected by scanning electron microscopy for the presence of bacteria at the interfaces.

Results  In the presence of the smear layer, RS and AP leaked significantly more slowly than in its absence. In the absence of the smear layer, AH leaked significantly more slowly than RS. SEM results indicated a differential pattern of bacterial penetration among the sealers.

Conclusions  Removal of the smear layer did not impair bacterial penetration along root canal fillings. A comparison of the sealers revealed no difference except that AH performed better than RS in the absence of the smear layer.
The effect of spreader size on fracture resistance of maxillary incisor roots
Authors: Pişkin B. , Aydın B. , Sarıkanat M.
Published: October 2007

Aim  To assess the effect of spreader size used during cold lateral compaction of gutta‐percha on fracture resistance of roots in maxillary incisor teeth.

Methodology  The crowns of 50 human maxillary incisor teeth having no carious lesions, no fracture or crazing were resected 2 mm coronal to the cemento‐enamel junction. The root canals of the teeth were prepared as follows: Group 1: No canal preparation. Group 2: Preparation using the stepback technique to a size 40 master apical file. Group 3: Canal preparation to size 40 and filling with laterally compacted gutta‐percha; the first spreader used was equal to size 40. Group 4: Same as group 3 except the first spreader was equal to size 35. Group 5: Same as group 3 except the first spreader was equal to size 25.

For each root, a simulated periodontal ligament was prepared. The roots were than mounted in polyester resin and fractured vertically on a universal testing machine (Shimadzu, Tokyo, Japan). The fracture values of teeth were analysed using Kruskal–Wallis and Mann–Whitney U‐tests (P = 0.05).

Results:  The uninstrumented group had the highest fracture resistance; instrumented, but unfilled roots, demonstrated the lowest resistance values (P = 0.009). There were no differences between the uninstrumented group and group 5 in which a size 25 spreader was used during filling. Use of spreaders larger than size 25 caused a significant reduction in fracture resistance of roots (P < 0.05).

Conclusion:  Spreader size used during lateral compaction of gutta‐percha can affect the fracture resistance of roots in extracted teeth.